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Sample records for basal transcription initiation

  1. Differentiation driven changes in the dynamic organization of Basal transcription initiation.

    Directory of Open Access Journals (Sweden)

    Giuseppina Giglia-Mari

    2009-10-01

    Full Text Available Studies based on cell-free systems and on in vitro-cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates and disassemble after reaction completion. This dynamic nature allows quick adaptation of transcription to changing conditions. However, it is unknown to what extent this dynamic transcription organization holds for postmitotic cells embedded in mammalian tissue. To allow analysis of transcription initiation dynamics directly into living mammalian tissues, we created a knock-in mouse model expressing fluorescently tagged TFIIH. Surprisingly and in contrast to what has been observed in cultured and proliferating cells, postmitotic murine cells embedded in their tissue exhibit a strong and long-lasting transcription-dependent immobilization of TFIIH. This immobilization is both differentiation driven and development dependent. Furthermore, although very statically bound, TFIIH can be remobilized to respond to new transcriptional needs. This divergent spatiotemporal transcriptional organization in different cells of the soma revisits the generally accepted highly dynamic concept of the kinetic framework of transcription and shows how basic processes, such as transcription, can be organized in a fundamentally different fashion in intact organisms as previously deduced from in vitro studies.

  2. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren;

    2008-01-01

    promoter docking of transcription initiation factors TFIID, TFIIB, and TFIIH on a gene containing a functional 5′ splice site. In addition to their promoter association, the TFIID and TFIIH components, TBP and p89, are specifically recruited to the 5′ splice site region. Our data suggest a model in which......Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin m......RNAs, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...

  3. Evolution and diversification of the basal transcription machinery.

    Science.gov (United States)

    Duttke, Sascha H C

    2015-03-01

    Transcription initiation was once thought to be regulated primarily by sequence-specific transcription factors with the basal transcription machinery being largely invariant. Gradually it became apparent that the basal transcription machinery greatly diversified during evolution and new studies now demonstrate that diversification of the TATA-binding protein (TBP) family yielded specialized and largely independent transcription systems.

  4. Direct Modulation of RNA Polymerase Core Functions by Basal Transcription Factors

    OpenAIRE

    Werner, Finn; Weinzierl, Robert O. J.

    2005-01-01

    Archaeal RNA polymerases (RNAPs) are recruited to promoters through the joint action of three basal transcription factors: TATA-binding protein, TFB (archaeal homolog of TFIIB), and TFE (archaeal homolog of TFIIE). Our results demonstrate several new insights into the mechanisms of TFB and TFE during the transcription cycle. (i) The N-terminal Zn ribbon of TFB displays a surprising degree of redundancy for the recruitment of RNAP during transcription initiation in the archaeal system. (ii) Th...

  5. Initiation of HIV Reverse Transcription

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    Roland Marquet

    2010-01-01

    Full Text Available Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

  6. Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2/TFIIH.

    NARCIS (Netherlands)

    A.J. van Vuuren (Hanneke); W. Vermeulen (Wim); L. Ma (Libin); G. Weeda (Geert); E. Appeldoorn (Esther); N.G.J. Jaspers (Nicolaas); A.J. van der Eb; J.H.J. Hoeijmakers (Jan); S. Humbert; L. Schaeffer; J-M. Egly (Jean-Marc)

    1994-01-01

    textabstractERCC3 was initially identified as a gene correcting the nucleotide excision repair (NER) defect of xeroderma pigmentosum complementation group B (XP-B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibil

  7. Cloned yeast and mammalian transcription factor TFIID gene products support basal but not activated metallothionein gene transcription

    International Nuclear Information System (INIS)

    Transcription factor IID (TFIID), the TATA binding factor, is thought to play a key role in the regulation of eukaryotic transcriptional initiation. The authors studied the role of TFIID in the transcription of the yeast metallothionein gene, which is regulated by the copper-dependent activator protein ACE1. Both basal and induced transcription of the metallothionein gene require TFIID and a functional TATA binding site. Crude human and mouse TFIID fractions, prepared from mammalian cells, respond to stimulation by ACE1, In contrast, human and yeast TFIID proteins expressed from the cloned genes do not respond to ACE1, except in the presence of what germ or yeast total cell extracts. These results indicate that the cloned TFIID gene products lack a component(s) or modifications(s) that is required for regulated as compared to basal transription

  8. TFB1 or TFB2 is sufficient for Thermococcus kodakaraensis viability and for basal transcription in vitro

    OpenAIRE

    Santangelo, Thomas J.; Čuboňová, L’ubomíra; James, Cindy L.; Reeve, John N.

    2006-01-01

    Archaeal RNA polymerases (RNAPs) are most similar to eukaryotic RNAP II (Pol II) but require the support of only two archaeal general transcription factors, TBP (TATA-box binding protein) and TFB (archaeal homologue of the eukaryotic general transcription factors TFIIB) to initiate basal transcription. However, many archaeal genomes encode more than one TFB and/or TBP leading to the hypothesis that different TFB/TBP combinations may be employed to direct initiation from different promoters in...

  9. TAF1B is a TFIIB-like component of the basal transcription machinery for RNA polymerase I.

    Science.gov (United States)

    Naidu, Srivatsava; Friedrich, J Karsten; Russell, Jackie; Zomerdijk, Joost C B M

    2011-09-16

    Transcription by eukaryotic RNA polymerases (Pols) II and III and archaeal Pol requires structurally related general transcription factors TFIIB, Brf1, and TFB, respectively, which are essential for polymerase recruitment and initiation events. A TFIIB-like protein was not evident in the Pol I basal transcription machinery. We report that TAF1B, a subunit of human Pol I basal transcription factor SL1, is structurally related to TFIIB/TFIIB-like proteins, through predicted amino-terminal zinc ribbon and cyclin-like fold domains. SL1, essential for Pol I recruitment to the ribosomal RNA gene promoter, also has an essential postpolymerase recruitment role, operating through TAF1B. Therefore, a TFIIB-related protein is implicated in preinitiation complex assembly and postpolymerase recruitment events in Pol I transcription, underscoring the parallels between eukaryotic Pol I, II, and III and archaeal transcription machineries. PMID:21921199

  10. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription.

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    Manuela Vanti

    2009-01-01

    Full Text Available Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5' end of HIV-1 transcribed region (5'HIV-TR, which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5'HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5'HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5'HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency.

  11. TAF7: traffic controller in transcription initiation.

    Science.gov (United States)

    Gegonne, Anne; Devaiah, Ballachanda N; Singer, Dinah S

    2013-01-01

    TAF7, a component of the TFIID complex, controls the first steps of transcription. It interacts with and regulates the enzymatic activities of transcription factors that regulate RNA polymerase II progression. Its diverse functions in transcription initiation are consistent with its essential role in cell proliferation.

  12. TBP Domain Symmetry in Basal and Activated Archaeal Transcription

    OpenAIRE

    Ouhammouch, Mohamed; Hausner, Winfried; Geiduschek, E Peter

    2008-01-01

    The TATA-box binding protein (TBP) is the platform for assembly of archaeal and eukaryotic transcription preinitiation complexes. Ancestral gene duplication and fusion events have produced the saddle-shaped TBP molecule, with its two direct-repeat subdomains and pseudo-two-fold symmetry. Collectively, eukaryotic TBPs have diverged from their present-day archaeal counterparts, which remain highly symmetrical. The similarity of the N- and C-halves of archaeal TBPs is especially pronounced in th...

  13. Molecular basis of transcription initiation in Archaea

    OpenAIRE

    De Carlo, Sacha; Lin, Shih-Chieh; Taatjes, Dylan J.; Hoenger, Andreas

    2010-01-01

    Compared with eukaryotes, the archaeal transcription initiation machinery—commonly known as the Pre-Initiation Complex—is relatively simple. The archaeal PIC consists of the TFIIB ortholog TFB, TBp and an 11-subunit RNA polymerase (RNAP). The relatively small size of the entire archaeal PIC makes it amenable to structural analysis. Using purified RNAP, TFB and TBP from the thermophile Pyrococcus furiosus, we assembled the biochemically active PIC at 65°C. The intact archaeal PIC was isolated ...

  14. Transcription initiation complex structures elucidate DNA opening.

    Science.gov (United States)

    Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

    2016-05-19

    Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

  15. Stimulation of basal transcription from the mouse mammary tumor virus promoter by Oct proteins.

    OpenAIRE

    Kim, M. H.; Peterson, D O

    1995-01-01

    The steroid hormone-inducible promoter of mouse mammary tumor virus (MMTV) contains three overlapping sequences related to the consensus octamer motif ATGCAAAT. Basal promoter activity in the absence of hormone induction from a template in which all three octamer elements were mutated was decreased by two-to threefold in in vitro transcription assays. Oct-1 protein purified from HeLa cell nuclear extracts, as well as recombinant Oct-1 expressed in bacteria, recognized MMTV octamer-related seq...

  16. Molecular basis of transcription initiation in Archaea.

    Science.gov (United States)

    De Carlo, Sacha; Lin, Shih-Chieh; Taatjes, Dylan J; Hoenger, Andreas

    2010-01-01

    Compared with eukaryotes, the archaeal transcription initiation machinery-commonly known as the Pre-Initiation Complex-is relatively simple. The archaeal PIC consists of the TFIIB ortholog TFB, TBP, and an 11-subunit RNA polymerase (RNAP). The relatively small size of the entire archaeal PIC makes it amenable to structural analysis. Using purified RNAP, TFB, and TBP from the thermophile Pyrococcus furiosus, we assembled the biochemically active PIC at 65ºC. The intact archaeal PIC was isolated by implementing a cross-linking technique followed by size-exclusion chromatography, and the structure of this 440 kDa assembly was determined using electron microscopy and single-particle reconstruction techniques. Combining difference maps with crystal structure docking of various sub-domains, TBP and TFB were localized within the macromolecular PIC. TBP/TFB assemble near the large RpoB subunit and the RpoD/L "foot" domain behind the RNAP central cleft. This location mimics that of yeast TBP and TFIIB in complex with yeast RNAP II. Collectively, these results define the structural organization of the archaeal transcription machinery and suggest a conserved core PIC architecture. PMID:21326901

  17. Molecular basis of transcription initiation in Archaea.

    Science.gov (United States)

    De Carlo, Sacha; Lin, Shih-Chieh; Taatjes, Dylan J; Hoenger, Andreas

    2010-01-01

    Compared with eukaryotes, the archaeal transcription initiation machinery-commonly known as the Pre-Initiation Complex-is relatively simple. The archaeal PIC consists of the TFIIB ortholog TFB, TBP, and an 11-subunit RNA polymerase (RNAP). The relatively small size of the entire archaeal PIC makes it amenable to structural analysis. Using purified RNAP, TFB, and TBP from the thermophile Pyrococcus furiosus, we assembled the biochemically active PIC at 65ºC. The intact archaeal PIC was isolated by implementing a cross-linking technique followed by size-exclusion chromatography, and the structure of this 440 kDa assembly was determined using electron microscopy and single-particle reconstruction techniques. Combining difference maps with crystal structure docking of various sub-domains, TBP and TFB were localized within the macromolecular PIC. TBP/TFB assemble near the large RpoB subunit and the RpoD/L "foot" domain behind the RNAP central cleft. This location mimics that of yeast TBP and TFIIB in complex with yeast RNAP II. Collectively, these results define the structural organization of the archaeal transcription machinery and suggest a conserved core PIC architecture.

  18. Sp1 and KLF15 regulate basal transcription of the human LRP5 gene

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    Zou Yongxin

    2010-02-01

    Full Text Available Abstract Background LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear. Results In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs. Conclusions Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.

  19. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

    Science.gov (United States)

    Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

    2013-01-01

    The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

  20. Basal transcription machinery: role in regulation of stress response in eukaryotes

    Indian Academy of Sciences (India)

    Parag Sadhale; Jiyoti Verma; Aruna Naorem

    2007-04-01

    The holoenzyme of prokaryotic RNA polymerase consists of the core enzyme, made of two , , ’ and subunits, which lacks promoter selectivity and a sigma () subunit which enables the core enzyme to initiate transcription in a promoter dependent fashion. A stress sigma factor s, in prokaryotes seems to regulate several stress response genes in conjunction with other stress specific regulators. Since the basic principles of transcription are conserved from simple bacteria to multicellular complex organisms, an obvious question is: what is the identity of a counterpart of s, that is closest to the core polymerase and that dictates transcription of stress regulated genes in general? In this review, we discuss the logic behind the suggestion that like in prokaryotes, eukaryotes also have a common functional unit in the transcription machinery through which the stress specific transcription factors regulate rapid and highly controlled induction of gene expression associated with generalized stress response and point to some candidates that would fit the bill of the eukaryotic s.

  1. Organization of the human mitochondrial transcription initiation complex

    OpenAIRE

    Yakubovskaya, Elena; Guja, Kip E.; Eng, Edward T.; Choi, Woo Suk; Mejia, Edison; Beglov, Dmitri; Lukin, Mark; Kozakov, Dima; Garcia-Diaz, Miguel

    2014-01-01

    Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein–protein interactions might help m...

  2. CoSMoS unravels mysteries of transcription initiation.

    Science.gov (United States)

    Gourse, Richard L; Landick, Robert

    2012-02-17

    Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters.

  3. CoSMoS Unravels Mysteries of Transcription Initiation

    OpenAIRE

    Gourse, Richard L.; Landick, Robert

    2012-01-01

    Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters.

  4. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation.

    Science.gov (United States)

    Peters, A; Storb, U

    1996-01-01

    To identify DNA sequences that target the somatic hypermutation process, the immunoglobulin gene promoter located upstream of the variable (V) region was duplicated upstream of the constant (C) region of a kappa transgene. Normally, kappa genes are somatically mutated only in the VJ region, but not in the C region. In B cell hybridomas from mice with this kappa transgene (P5'C), both the VJ region and the C region, but not the region between them, were mutated at similar frequencies, suggesting that the mutation mechanism is related to transcription. The downstream promoter was not occluded by transcripts from the upstream promoter. In fact, the levels of transcripts originating from the two promoters were similar, supporting a mutation model based on initiation of transcripts. Several "hot-spots" of somatic mutation were noted, further demonstrating that this transgene has the hallmarks of somatic mutation of endogenous immunoglobulin genes. A model linking somatic mutation to transcription-coupled DNA repair is proposed.

  5. Initiation and regulation of paramyxovirus transcription and replication.

    Science.gov (United States)

    Noton, Sarah L; Fearns, Rachel

    2015-05-01

    The paramyxovirus family has a genome consisting of a single strand of negative sense RNA. This genome acts as a template for two distinct processes: transcription to generate subgenomic, capped and polyadenylated mRNAs, and genome replication. These viruses only encode one polymerase. Thus, an intriguing question is, how does the viral polymerase initiate and become committed to either transcription or replication? By answering this we can begin to understand how these two processes are regulated. In this review article, we present recent findings from studies on the paramyxovirus, respiratory syncytial virus, which show how its polymerase is able to initiate transcription and replication from a single promoter. We discuss how these findings apply to other paramyxoviruses. Then, we examine how trans-acting proteins and promoter secondary structure might serve to regulate transcription and replication during different phases of the paramyxovirus replication cycle.

  6. A code for transcription initiation in mammalian genomes

    DEFF Research Database (Denmark)

    Frith, Martin C.; Valen, Eivind Dale; Krogh, Anders;

    2007-01-01

    that initiation events are clustered on the chromosomes at multiple scales - clusters within clusters - indicating multiple regulatory processes. Within the smallest of such clusters, which can be interpreted as core promoters, the local DNA sequence predicts the relative transcription start usage of each...... of large- and small-scale effects: the selection of transcription start sites is largely governed by the local DNA sequence, whereas the transcriptional activity of a locus is regulated at a different level; it is affected by distal features or events such as enhancers and chromatin remodeling....

  7. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P;

    1995-01-01

    have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes...... and contains relatively GC-rich proximal sequences. A subregion of this sequence, highly conserved between human and murine genes, contains most of the promoter activity and is specifically bound by HeLa nuclear proteins, one of which belongs to the SP1 class....

  8. The evolutionary diversification of LSF and Grainyhead transcription factors preceded the radiation of basal animal lineages

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    Kaufman Les

    2010-04-01

    Full Text Available Abstract Background The transcription factors of the LSF/Grainyhead (GRH family are characterized by the possession of a distinctive DNA-binding domain that bears no clear relationship to other known DNA-binding domains, with the possible exception of the p53 core domain. In triploblastic animals, the LSF and GRH subfamilies have diverged extensively with respect to their biological roles, general expression patterns, and mechanism of DNA binding. For example, Grainyhead (GRH homologs are expressed primarily in the epidermis, and they appear to play an ancient role in maintaining the epidermal barrier. By contrast, LSF homologs are more widely expressed, and they regulate general cellular functions such as cell cycle progression and survival in addition to cell-lineage specific gene expression. Results To illuminate the early evolution of this family and reconstruct the functional divergence of LSF and GRH, we compared homologs from 18 phylogenetically diverse taxa, including four basal animals (Nematostella vectensis, Vallicula multiformis, Trichoplax adhaerens, and Amphimedon queenslandica, a choanoflagellate (Monosiga brevicollis and several fungi. Phylogenetic and bioinformatic analyses of these sequences indicate that (1 the LSF/GRH gene family originated prior to the animal-fungal divergence, and (2 the functional diversification of the LSF and GRH subfamilies occurred prior to the divergence between sponges and eumetazoans. Aspects of the domain architecture of LSF/GRH proteins are well conserved between fungi, choanoflagellates, and metazoans, though within the Metazoa, the LSF and GRH families are clearly distinct. We failed to identify a convincing LSF/GRH homolog in the sequenced genomes of the algae Volvox carteri and Chlamydomonas reinhardtii or the amoebozoan Dictyostelium purpureum. Interestingly, the ancestral GRH locus has become split into two separate loci in the sea anemone Nematostella, with one locus encoding a DNA binding

  9. Tat gets the "green" light on transcription initiation

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    Kashanchi Fatah

    2005-11-01

    Full Text Available Abstract Human immunodeficiency virus type 1 (HIV-1 Tat transactivation is an essential step in the viral life cycle. Over the past several years, it has become widely accepted that Tat exerts its transcriptional effect by binding the transactivation-responsive region (TAR and enhancing transcriptional elongation. Consistent with this hypothesis, it has been shown that Tat promotes the binding of P-TEFb, a transcription elongation factor composed of cyclin T1 and cdk9, and the interaction of Tat with P-TEFb and TAR leads to hyperphosphorylation of the C-terminal domain (CTD of RNA Pol II and increased processivity of RNA Pol II. A recent report, however, has generated renewed interest that Tat may also play a critical role in transcription complex (TC assembly at the preinitiation step. Using in vivo chromatin immunoprecipitation assays, the authors reported that the HIV TC contains TBP but not TBP-associated factors. The stimulatory effect involved the direct interaction of Tat and P-TEFb and was evident at the earliest step of TC assembly, the TBP-TATA box interaction. In this article, we will review this data in context of earlier data which also support Tat's involvement in transcriptional complex assembly. Specifically, we will discuss experiments which demonstrated that Tat interacted with TBP and increased transcription initiation complex stability in cell free assays. We will also discuss studies which demonstrated that over expression of TBP alone was sufficient to obtain Tat activated transcription in vitro and in vivo. Finally, studies using self-cleaving ribozymes which suggested that Tat transactivation was not compatible with pausing of the RNA Pol II at the TAR site will be discussed.

  10. Stress-and Pathogen-Induced Arabidopsis WRKY48 is a Transcriptional Activator that Represses Plant Basal Defense

    Institute of Scientific and Technical Information of China (English)

    Deng-Hui Xing; Zi-Bing Lai; Zu-Yu Zheng; K. M. Vinod; Bao-Fang Fan; Zhi-Xiang Chen

    2008-01-01

    Plant WRKY transcription factors can function as either positive or negative regulators of plant basal disease resistance. Arabidopsis WRKY48 is induced by mechanical and/or osmotic stress due to infiltration and pathogen infection and, therefore, may play a role in plant defense responses. WRKY48 is localized to the nucleus, recognizes the TrGACC Wbox sequence with a high affinity in vitro and functions in plant cells as a strong transcriptional activator. To determine the biological functions directly, we have isolated loss-of-function T-DNA insertion mutants and generated gain-of-function transgenic overexpression plants for WRKY48 in Arabidopsis. Growth of a virulent strain of the bacterial pathogen Pseudomonas syringae was decreased in the wrky48T-DNA insertion mutants. The enhanced resistance of the loss-of-function mutants was associated with increased induction of salicylic acid-regulated PR1 by the bacterial pathogen. By contrast, transgenic WRKY48-0verexpressing plants support enhanced growth of P syringae and the enhanced susceptibility was associated with reduced expression of defense-related PR genes. These results suggest that WRKY48 is a negative regulator of PR gene expression and basal resistance to the bacterial pathogen P syringae.

  11. Tick-box for 3'-end formation of mitochondrial transcripts in Ixodida, basal chelicerates and Drosophila.

    Directory of Open Access Journals (Sweden)

    Matteo Montagna

    Full Text Available According to the tRNA punctuation model, the mitochondrial genome (mtDNA of mammals and arthropods is transcribed as large polycistronic precursors that are maturated by endonucleolytic cleavage at tRNA borders and RNA polyadenylation. Starting from the newly sequenced mtDNA of Ixodes ricinus and using a combination of mitogenomics and transcriptional analyses, we found that in all currently-sequenced tick lineages (Prostriata, Metastriata and Argasidae the 3'-end of the polyadenylated nad1 and rrnL transcripts does not follow the tRNA punctuation model and is located upstream of a degenerate 17-bp DNA motif. A slightly different motif is also present downstream the 3'-end of nad1 transcripts in the primitive chelicerate Limulus polyphemus and in Drosophila species, indicating the ancient origin and the evolutionary conservation of this motif in arthropods. The transcriptional analyses suggest that this motif directs the 3'-end formation of the nad1/rrnL mature RNAs, likely working as a transcription termination signal or a processing signal of precursor transcripts. Moreover, as most regulatory elements, this motif is characterized by a taxon-specific evolution. Although this signal is not exclusive of ticks, making a play on words it has been named "Tick-Box", since it is a check mark that has to be verified for the 3'-end formation of some mt transcripts, and its consensus sequence has been here carefully characterized in ticks. Indeed, in the whole mtDNA of all ticks, the Tick-Box is always present downstream of nad1 and rrnL, mainly in non-coding regions (NCRs and occasionally within trnL(CUN. However, some metastriates present a third Tick-Box at an intriguing site--inside the small NCR located at one end of a 3.4 kb translocated region, the other end of which exhibits the nad1 Tick-Box--hinting that this motif could have been involved in metastriate gene order rearrangements.

  12. Widespread suppression of intragenic transcription initiation by H-NS

    OpenAIRE

    Singh, Shivani S.; Singh, Navjot; Bonocora, Richard P.; Fitzgerald, Devon M.; Wade, Joseph T.; Grainger, David C.

    2014-01-01

    H-NS is a bacterial folding factor that has been implicated in the silencing of horizontally acquired genes. These genes are thought to be toxic by virtue of their A/T content. Here, Singh et al. show that a major, long-overlooked function of H-NS is to prevent widespread initiation of noncoding transcripts within foreign genes. This study provides a molecular rationalization for the toxicity of horizontally acquired DNA and explains how this is counteracted by H-NS.

  13. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    Science.gov (United States)

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. PMID:27472897

  14. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

    Science.gov (United States)

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

  15. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    Science.gov (United States)

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-07-29

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

  16. Tetracycline-controlled transcriptional regulation systems:countermeasures to eliminate basal transgene leaks in Tet-based systems

    Institute of Scientific and Technical Information of China (English)

    XIAO Dong; SUN Yan; GU Weiwang; CHEN Xigu

    2007-01-01

    To analyze the function of any given transgene(s) accurately in transgenic mice, and to produce credible transgenic animal models of various human diseases (precisely and realistically mimicking disease states), it is critical to be able to control gene expression in the animals conditionally. The ability to switch gene expression "on" or "off" in the restricted cells or tissue(s) at specific time(s)allows unprecedented flexibility for exploring gene function(s) in both the health and the disease. Pioneering work on inducible transgene expression has led to the development of a wide variety of controlled gene expression systems that meet this criterion. Among them, the tetracycline-inducible systems (e. g. Tet-off and Tet-on) have been widely, frequently and successfully employed in vitro and in vivo.These systems, however, are not always tight but leaky; sometimes the leakage is significant. In some circumstances, the resulting leak is acceptable, but in others, it is more problematic. Though these systems face this disadvantage, i.e. basal transgene leakage in vitro and in vivo, several approaches, including using improved versions (e. g. rtTA2S-M2 and rtTA2S-S2) of rtTA, tetracycline-controlled transcriptional silencer (tTS), an "ideal" minimal promoter in responsive components or combinations thereof, have been developed to avoid this limitation effectively. In this review we discuss the countermeasures available to eliminate basal transgene leakage from Tet-based systems.

  17. The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans

    Directory of Open Access Journals (Sweden)

    Groner Yoram

    2008-08-01

    Full Text Available Abstract Background Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFβ, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals. Results In this study, we detect and characterize the hitherto unexplored Runx/CBFβ genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFβ-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFβ dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFβ are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors. Conclusion These results reveal that Runx and CBFβ likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFβ-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

  18. A new way to start: nanoRNA-mediated priming of transcription initiation.

    Science.gov (United States)

    Nickels, Bryce E

    2012-01-01

    A recent study provides evidence that RNA polymerase uses 2- to ~4-nt RNAs, species termed "nanoRNAs," to prime transcription initiation in Escherichia coli. Priming of transcription initiation with nanoRNAs represents a previously undocumented component of transcription start site selection and gene expression.

  19. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number.

    Science.gov (United States)

    Campbell, Christopher T; Kolesar, Jill E; Kaufman, Brett A

    2012-01-01

    Mitochondrial transcription factor A (mtTFA, mtTF1, TFAM) is an essential protein that binds mitochondrial DNA (mtDNA) with and without sequence specificity to regulate both mitochondrial transcription initiation and mtDNA copy number. The abundance of mtDNA generally reflects TFAM protein levels; however, the precise mechanism(s) by which this occurs remains a matter of debate. Data suggest that the usage of mitochondrial promoters is regulated by TFAM dosage, allowing TFAM to affect both gene expression and RNA priming for first strand mtDNA replication. Additionally, TFAM has a non-specific DNA binding activity that is both cooperative and high affinity. TFAM can compact plasmid DNA in vitro, suggesting a structural role for the non-specific DNA binding activity in genome packaging. This review summarizes TFAM-mtDNA interactions and describes an emerging view of TFAM as a multipurpose coordinator of mtDNA transactions, with direct consequences for the maintenance of gene expression and genome copy number. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. PMID:22465614

  20. Low Trichorhinophalangeal Syndrome 1 Gene Transcript Levels in Basal-like Breast Cancer Associate with Mesenchymal-to-epithelial Transition

    Institute of Scientific and Technical Information of China (English)

    Yi Bao; Ling-juan Ruan; Juan-fen Mo

    2013-01-01

    Objective To investigate trichorhinophalangeal syndrome 1 gene (TRPS-1) expression patterns in different subtypes of breast cancer and its correlations with other genes and survival using microarray data sets. Methods The transcripts of TRPS-1 and its role in survival in breast cancer were analyzed using published microarray data sets-Netherlands Cancer Institute (NKI) cohort andWang cohort. Results TRPS-1 expression was lower in basal-like breast cancer. The mRNA levels of TRPS-1 negatively correlated with Slug (Pearson correlation coefficient=−0.1366, P=0.0189 in NKI data set and Pearson correlation coefficient=−0.1571, P=0.0078 in Wang data set), FOXC1 (Pearson correlation coefficient=−0.1211, P=0.0376 in NKI data set and Pearson correlation coefficient=−0.1709, P=0.0037 in Wang data set), and CXCL1 (Pearson correlation coefficient=−0.1197, P=0.0399 in NKI data set and Pearson correlation coefficient=−0.3436, P Conclusion The strong expression of TRPS-1 may serve as a good prognostic marker in breast cancer.

  1. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese;

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors....... We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed...

  2. Footprinting of ribosomal RNA genes by transcription initiation factor and RNA polymerase I.

    OpenAIRE

    Bateman, E.; Iida, C T; Kownin, P; Paule, M R

    1985-01-01

    The binding of a species-specific transcription initiation factor (TIF) and purified RNA polymerase I to the promoter region of the 39S ribosomal RNA gene from Acanthamoeba were studied by using DNase I "footprinting." Conditions were chosen such that the footprints obtained could be correlated with the transcriptional activity of the TIF-containing fractions used and that the labeled DNA present would itself serve as a template for transcription. The transcription factor binds upstream from ...

  3. Post-transcriptional regulation of cytokine mRNA controls the initiation and resolution of inflammation.

    OpenAIRE

    Mino, Takashi; Takeuchi, Osamu

    2013-01-01

    Cytokines are critical mediators of inflammation and host defense. Cytokine production is regulated during transcription and post-transcription. Post-transcriptional regulation modifies mRNA stability and translation, allowing for the rapid and flexible control of gene expression, which is important for coordinating the initiation and resolution of inflammation. We review here a variety of post-transcriptional control mechanisms that regulate inflammation and discuss how these mechanisms are ...

  4. Events during Initiation of Archaeal Transcription: Open Complex Formation and DNA-Protein Interactions

    OpenAIRE

    Hausner, Winfried; Thomm, Michael

    2001-01-01

    Transcription in Archaea is initiated by association of a TATA box binding protein (TBP) with a TATA box. This interaction is stabilized by the binding of the transcription factor IIB (TFIIB) orthologue TFB. We show here that the RNA polymerase of the archaeon Methanococcus, in contrast to polymerase II, does not require hydrolysis of the β-γ bond of ATP for initiation of transcription and open complex formation on linearized DNA. Permanganate probing revealed that the archaeal open complex s...

  5. The core human mitochondrial transcription initiation complex: It only takes two to tango

    OpenAIRE

    Shutt, Timothy E.; Bestwick, Megan; Shadel, Gerald S.

    2011-01-01

    We recently demonstrated that the core transcription initiation complex in human mitochondria is a two-component system (POLRMT and h-mtTFB2). Human mtTFA/TFAM, previously proposed to be a requisite initiation complex member, is dispensable for promoter-specific initiation in vitro. We propose that it instead regulates relative promoter activity and/or overall nucleoid transcription and replication potential.

  6. Analysis of the transcription initiation mechanism of tomato spotted wilt virus

    NARCIS (Netherlands)

    Duijsings, D.M.J.M.

    2001-01-01

    Genome replication and transcription of Tomato spotted wilt virus (TSWV, genus Tospovirus ) follows in most aspects the general rules for negative strand RNA viruses with segmented genomes. One common feature is the occurrence of "cap snatching" during transcription initiation. During this process,

  7. Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis

    NARCIS (Netherlands)

    C. Nepal (Chirag); Y. Hadzhiev (Yavor); C. Previti (Christopher); V. Haberle (Vanja); N. Li (Nan); H. Takahashi (Hiroyuki); A.M. Suzuki (Ana Maria); Y. Sheng (Ying); R.F. Abdelhamid (Rehab); S. Anand (Santosh); P.A. Gehrig (Paola A.); A. Akalin (Altuna); C. Kockx (Christel); A. Van Der Sloot (Antoine); W.F.J. van IJcken (Wilfred); O. Armant (Olivier); S. Rastegar (Sepand); C. Watson (Craig); U. Strähle (Uwe); E. Stupka (Elia); P. Carninci (Piero); B. Lenhard (Boris); F. Müller (Ferenc)

    2013-01-01

    textabstractSpatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we provid

  8. The interaction between bacterial transcription factors and RNA polymerase during the transition from initiation to elongation.

    Science.gov (United States)

    Yang, Xiao; Lewis, Peter J

    2010-01-01

    There are three stages of transcription: initiation, elongation and termination, and traditionally there has been a clear distinction between the stages. The specificity factor sigma is completely released from bacterial RNA polymerase after initiation, and then recycled for another round of transcription. Elongation factors then associate with the polymerase followed by termination factors (where necessary). These factors dissociate prior to initiation of a new round of transcription. However, there is growing evidence suggesting that sigma factors can be retained in the elongation complex. The structure of bacterial RNAP in complex with an essential elongation factor NusA has recently been published, which suggested rather than competing for the major σ binding site, NusA binds to a discrete region on RNAP. A model was proposed to help explain the way in which both factors could be associated with RNAP during the transition from transcription initiation to elongation.

  9. Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

    DEFF Research Database (Denmark)

    Chen, Yun; Pai, Athma A; Herudek, Jan;

    2016-01-01

    Mammalian transcriptomes are complex and formed by extensive promoter activity. In addition, gene promoters are largely divergent and initiate transcription of reverse-oriented promoter upstream transcripts (PROMPTs). Although PROMPTs are commonly terminated early, influenced by polyadenylation...... sites, promoters often cluster so that the divergent activity of one might impact another. Here we found that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT...... formation, but owing to polyadenylation site constraints, these transcripts tend to spread into the neighboring mRNA on the same strand. This mechanism to derive new alternative mRNA transcription start sites (TSSs) is also evident at closely spaced promoters supporting convergent mRNA transcription. We...

  10. Large heterogeneity of mitochondrial DNA transcription and initiation of replication exposed by single-cell imaging.

    Science.gov (United States)

    Chatre, Laurent; Ricchetti, Miria

    2013-02-15

    Mitochondrial DNA (mtDNA) replication and transcription are crucial for cell function, but these processes are poorly understood at the single-cell level. We describe a novel fluorescence in situ hybridization protocol, called mTRIP (mitochondrial transcription and replication imaging protocol), that reveals simultaneously mtDNA and RNA, and that can also be coupled to immunofluorescence for in situ protein examination. mTRIP reveals mitochondrial structures engaged in initiation of DNA replication by identification of a specific sequence in the regulatory D-loop, as well as unique transcription profiles in single human cells. We observe and quantify at least three classes of mitochondrial structures: (i) replication initiation active and transcript-positive (Ia-Tp); (ii) replication initiation silent and transcript-positive (Is-Tp); and (iii) replication initiation silent and transcript-negative (Is-Tn). Thus, individual mitochondria are dramatically heterogeneous within the same cell. Moreover, mTRIP exposes a mosaic of distinct nucleic acid patterns in the D-loop, including H-strand versus L-strand transcripts, and uncoupled rRNA transcription and mtDNA initiation of replication, which might have functional consequences in the regulation of the mtDNA. Finally, mTRIP identifies altered mtDNA processing in cells with unbalanced mtDNA content and function, including in human mitochondrial disorders. Thus, mTRIP reveals qualitative and quantitative alterations that provide additional tools for elucidating the dynamics of mtDNA processing in single cells and mitochondrial dysfunction in diseases.

  11. Effects of rate-limiting steps in transcription initiation on genetic filter motifs.

    Science.gov (United States)

    Häkkinen, Antti; Tran, Huy; Yli-Harja, Olli; Ribeiro, Andre S

    2013-01-01

    The behavior of genetic motifs is determined not only by the gene-gene interactions, but also by the expression patterns of the constituent genes. Live single-molecule measurements have provided evidence that transcription initiation is a sequential process, whose kinetics plays a key role in the dynamics of mRNA and protein numbers. The extent to which it affects the behavior of cellular motifs is unknown. Here, we examine how the kinetics of transcription initiation affects the behavior of motifs performing filtering in amplitude and frequency domain. We find that the performance of each filter is degraded as transcript levels are lowered. This effect can be reduced by having a transcription process with more steps. In addition, we show that the kinetics of the stepwise transcription initiation process affects features such as filter cutoffs. These results constitute an assessment of the range of behaviors of genetic motifs as a function of the kinetics of transcription initiation, and thus will aid in tuning of synthetic motifs to attain specific characteristics without affecting their protein products.

  12. Making ends meet: Coordination between RNA 3'end processing and transcription initiation

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Jensen, Torben Heick; Lykke-Andersen, Søren

    2013-01-01

    RNA polymerase II (RNAPII)-mediated gene transcription initiates at promoters and ends at terminators. Transcription termination is intimately connected to 3'-end processing of the produced RNA and already when loaded at the promoter, RNAPII starts to become configured for this downstream event....... Conversely, RNAPII is 'reset' as part of the 3'-end processing/termination event, thus preparing the enzyme for its next round of transcription--possibly on the same gene. There is both direct and circumstantial evidence for preferential recycling of RNAPII from the gene terminator back to its own promoter...

  13. HTLV-I antisense transcripts initiating in the 3'LTR are alternatively spliced and polyadenylated

    Directory of Open Access Journals (Sweden)

    Marriott Susan J

    2006-03-01

    Full Text Available Abstract Background Antisense transcription in retroviruses has been suggested for both HIV-1 and HTLV-I, although the existence and coding potential of these transcripts remain controversial. Thorough characterization is required to demonstrate the existence of these transcripts and gain insight into their role in retrovirus biology. Results This report provides the first complete characterization of an antisense retroviral transcript that encodes the previously described HTLV-I HBZ protein. In this study, we show that HBZ-encoding transcripts initiate in the 3' long terminal repeat (LTR at several positions and consist of two alternatively spliced variants (SP1 and SP2. Expression of the most abundant HBZ spliced variant (SP1 could be detected in different HTLV-I-infected cell lines and importantly in cellular clones isolated from HTLV-I-infected patients. Polyadenylation of HBZ RNA occurred at a distance of 1450 nucleotides downstream of the HBZ stop codon in close proximity of a typical polyA signal. We have also determined that translation mostly initiates from the first exon located in the 3' LTR and that the HBZ isoform produced from the SP1 spliced variant demonstrated inhibition of Tax and c-Jun-dependent transcriptional activation. Conclusion These results conclusively demonstrate the existence of antisense transcription in retroviruses, which likely plays a role in HTLV-I-associated pathogenesis through HBZ protein synthesis.

  14. A retrospective database analysis of insulin use patterns in insulin-naïve patients with type 2 diabetes initiating basal insulin or mixtures

    OpenAIRE

    Bonafede, Machaon MK; Kalsekar, Anupama; Pawaskar, Manjiri; Ruiz, Kimberly M; Torres, Amelito M; Kelly, Karen R.; Curkendall, Suellen M

    2010-01-01

    Objective: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence. Research design and methods: The Thomson Reuters MarketScan® databases were used to retrospectively analyze insulin-naïve patients with type 2 diabetes by initiating insulin therapy. Insulin use was described using a variety of measures. The persistence to insulin was described using both a gap-ba...

  15. Regulation of axillary meristem initiation by transcription factors and plant hormones

    Directory of Open Access Journals (Sweden)

    Minglei eYang

    2016-02-01

    Full Text Available One distinctive feature of plant post-embryonic development is that plants can undergo reiterative growth and continuous organogenesis throughout their lifetimes. Axillary meristems in leaf axils play a central role in this growth and differences in meristem initiation and development produce the diversity of plant architecture. Studies in the past fifteen years have shown that several transcription factors and phytohormones affect axillary meristem initiation. In this review, we highlight recent research using systems biology approaches to examine the regulatory hierarchies underlying axillary meristem initiation and the role of auxins and cytokinins in axillary meristem initiation and development. This research revealed a developmental mechanism in which phytohormone signals act with a gene regulatory network containing multiple transcription factors to contribute to the initiation of axillary meristems.

  16. The HaDREB2 transcription factor enhances basal thermotolerance and longevity of seeds through functional interaction with HaHSFA9

    Directory of Open Access Journals (Sweden)

    Carranco Raúl

    2009-06-01

    Full Text Available Abstract Background Transcription factor HaDREB2 was identified in sunflower (Helianthus annuus L. as a drought-responsive element-binding factor 2 (DREB2 with unique properties. HaDREB2 and the sunflower Heat Shock Factor A9 (HaHSFA9 co-activated the Hahsp17.6G1 promoter in sunflower embryos. Both factors could be involved in transcriptional co-activation of additional small heat stress protein (sHSP promoters, and thus contribute to the HaHSFA9-mediated enhancement of longevity and basal thermotolerance of seeds. Results We found that overexpression of HaDREB2 in seeds did not enhance longevity. This was deduced from assays of basal thermotolerance and controlled seed-deterioration, which were performed with transgenic tobacco. Furthermore, the constitutive overexpression of HaDREB2 did not increase thermotolerance in seedlings or result in the accumulation of HSPs at normal growth temperatures. In contrast, when HaDREB2 and HaHSFA9 were conjointly overexpressed in seeds, we observed positive effects on seed longevity, beyond those observed with overexpression of HaHSFA9 alone. Such additional effects are accompanied by a subtle enhancement of the accumulation of subsets of sHSPs belonging to the CI and CII cytosolic classes. Conclusion Our results reveal the functional interdependency of HaDREB2 and HaHSFA9 in seeds. HaDREB2 differs from other previously characterized DREB2 factors in plants in terms of its unique functional interaction with the seed-specific HaHSFA9 factor. No functional interaction between HaDREB2 and HaHSFA9 was observed when both factors were conjointly overexpressed in vegetative tissues. We therefore suggest that additional, seed-specific factors, or protein modifications, could be required for the functional interaction between HaDREB2 and HaHSFA9.

  17. Regulation of Axillary Meristem Initiation by Transcription Factors and Plant Hormones

    OpenAIRE

    Yang, Minglei; Jiao, Yuling

    2016-01-01

    One distinctive feature of plant post-embryonic development is that plants can undergo reiterative growth and continuous organogenesis throughout their lifetimes. Axillary meristems (AMs) in leaf axils play a central role in this growth and differences in meristem initiation and development produce the diversity of plant architecture. Studies in the past 15 years have shown that several transcription factors (TFs) and phytohormones affect AM initiation. In this review, we highlight recent res...

  18. Preferential use of RNA leader sequences during influenza A transcription initiation in vivo

    NARCIS (Netherlands)

    Geerts-Dimitriadou, C.; Goldbach, R.W.; Kormelink, R.J.M.

    2011-01-01

    In vitro transcription initiation studies revealed a preference of influenza A virus for capped RNA leader sequences with base complementarity to the viral RNA template. Here, these results were verified during an influenza infection in MDCK cells. Alfalfa mosaic virus RNA3 leader sequences mutated

  19. TBP binding and the rate of transcription initiation from the human β-globin gene.

    NARCIS (Netherlands)

    M. Antoniou (Michael); E. Spanopoulou; F.G. Grosveld (Frank); E. de Boer (Ernie)

    1995-01-01

    textabstractDNA-protein interaction studies in vitro revealed several factors binding over the TATA box and the region of transcription initiation (cap) site of the human beta-globin promoter; TATA binding protein TBP at -30, Sp1 at -19, GATA-1 at -12 and +5, YY1 at -9 and a novel factor C1 over the

  20. Dependence of Proximal GC Boxes and Binding Transcription Factors in the Regulation of Basal and Valproic Acid-Induced Expression of t-PA

    Directory of Open Access Journals (Sweden)

    Erik Ulfhammer

    2016-01-01

    Full Text Available Objective. Endothelial tissue-type plasminogen activator (t-PA release is a pivotal response to protect the circulation from occluding thrombosis. We have shown that the t-PA gene is epigenetically regulated and greatly induced by the histone deacetylase (HDAC inhibitor valproic acid (VPA. We now investigated involvement of known t-PA promoter regulatory elements and evaluated dependence of potential interacting transcription factors/cofactors. Methods. A reporter vector with an insert, separately mutated at either the t-PA promoter CRE or GC box II or GC box III elements, was transfected into HT-1080 and HUVECs and challenged with VPA. HUVECs were targeted with siRNA against histone acetyl transferases (HAT and selected transcription factors from the Sp/KLF family. Results. An intact VPA-response was observed with CRE mutated constructs, whereas mutation of GC boxes II and III reduced the magnitude of the induction by 54 and 79% in HT-1080 and 49 and 50% in HUVECs, respectively. An attenuated induction of t-PA mRNA was observed after Sp2, Sp4, and KLF5 depletion. KLF2 and p300 (HAT were identified as positive regulators of basal t-PA expression and Sp4 and KLF9 as repressors. Conclusion. VPA-induced t-PA expression is dependent on the proximal GC boxes in the t-PA promoter and may involve interactions with Sp2, Sp4, and KLF5.

  1. A retrospective database analysis of insulin use patterns in insulin-naïve patients with type 2 diabetes initiating basal insulin or mixtures

    OpenAIRE

    Bonafede, Machaon

    2010-01-01

    Machaon MK Bonafede1, Anupama Kalsekar2, Manjiri Pawaskar2, Kimberly M Ruiz3, Amelito M Torres3, Karen R Kelly2, Suellen M Curkendall31Thomson Reuters Inc, Cambridge, Massachusetts, USA; 2Eli Lilly and Company, Indianapolis, Indiana, USA; 3Thomson Reuters Inc, Washington, DC, USAObjective: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence.Research design and...

  2. Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: a potential regulator of involution

    OpenAIRE

    Thomas, E; Zeps, N.; Rigby, P; Hartmann, P

    2011-01-01

    Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that specifically target involution of the luminal cells in the alveoli but not the basal and ductal cells are poorly understood. In this study we show in cultured human mammary alveolar structures that the...

  3. Mechanisms of triplex DNA-mediated inhibition of transcription initiation in cells.

    Science.gov (United States)

    Jain, Aklank; Magistri, Marco; Napoli, Sara; Carbone, Giuseppina M; Catapano, Carlo V

    2010-03-01

    Triplex-forming oligonucleotides (TFOs) are attractive tools to control gene expression at the transcriptional level. This anti-gene approach has proven to be successful in various experimental settings. However, the mechanisms leading to transcriptional repression in cells have not been fully investigated yet. Here, we examined the consequence of triplex DNA formation on the binding of transcriptional activators, co-activators and RNA Polymerase II to the ets2 gene promoter using chromatin immunoprecipitation assays. The triplex target sequence was located approximately 40-bp upstream of the transcription start site (TSS) and overlapped an Sp1 binding site relevant for ets2 transcription. We found that the ets2-TFO prevented binding of Sp1, TAF(II)130 and TAF(II)250 to the ets2 promoter, while binding of RNA polymerase II and TBP were not affected. The effects were both sequence and target specific, since the TFO had no effect on the c-myc promoter and a mutated ets2 promoter construct. Thus, triplex DNA formation near a TSS leads to formation of a non-functional pre-initiation complex (PIC) by blocking binding of transcriptional activators and co-activator molecules. This is the first direct demonstration of interference with PIC assembly at the TSS by oligonucleotide-triplex DNA formation in cells. PMID:20045441

  4. X-ray Crystal Structures Elucidate the Nucleotidyl Transfer Reaction of Transcript Initiation Using Two Nucleotides

    Energy Technology Data Exchange (ETDEWEB)

    M Gleghorn; E Davydova; R Basu; L Rothman-Denes; K Murakami

    2011-12-31

    We have determined the X-ray crystal structures of the pre- and postcatalytic forms of the initiation complex of bacteriophage N4 RNA polymerase that provide the complete set of atomic images depicting the process of transcript initiation by a single-subunit RNA polymerase. As observed during T7 RNA polymerase transcript elongation, substrate loading for the initiation process also drives a conformational change of the O helix, but only the correct base pairing between the +2 substrate and DNA base is able to complete the O-helix conformational transition. Substrate binding also facilitates catalytic metal binding that leads to alignment of the reactive groups of substrates for the nucleotidyl transfer reaction. Although all nucleic acid polymerases use two divalent metals for catalysis, they differ in the requirements and the timing of binding of each metal. In the case of bacteriophage RNA polymerase, we propose that catalytic metal binding is the last step before the nucleotidyl transfer reaction.

  5. Internal translation initiation from HIV-1 transcripts is conferred by a common RNA structure.

    Science.gov (United States)

    Plank, Terra-Dawn M; Whitehurst, James T; Cencic, Regina; Pelletier, Jerry; Kieft, Jeffrey S

    2014-01-01

    Alternative splicing of the human immunodeficiency virus 1 (HIV-1) RNA transcripts produces mRNAs encoding nine different viral proteins. The leader of each contains a common non-coding exon at the 5' end. Previous studies showed that the leaders from the common exon-containing transcripts gag, nef, vif, vpr and vpu can direct protein synthesis through internal ribosome entry sites (IRESs) with varying efficiencies. Here we explored whether the common exon acts as an IRES element in the context of all the 5' leaders or if each harbors a distinct IRES. We also explored the relationship between the IRESs and initiation codon selection. We find that the common exon adopts a similar conformation in every leader we explored and that the sequence and structure is required for IRES activity. We also find that each leader uses a scanning mechanism for start codon identification. Together, our data point to a model in which the common exon on HIV-1 transcripts acts as the ribosome landing pad, recruiting preinitiation complexes upstream of the initiation codon, followed by scanning to each transcript's initiator AUG. PMID:26779399

  6. Tfb6, a previously unidentified subunit of the general transcription factor TFIIH, facilitates dissociation of Ssl2 helicase after transcription initiation

    OpenAIRE

    Murakami, Kenji; Gibbons, Brian J.; Ralph E Davis; Nagai, Shigeki; Liu, Xin; Robinson, Philip J. J.; Wu, Tinghe; Kaplan, Craig D; Kornberg, Roger D.

    2012-01-01

    General transcription factor TFIIH, previously described as a 10-subunit complex, is essential for transcription and DNA repair. An eleventh subunit now identified, termed Tfb6, exhibits 45% sequence similarity to human nuclear mRNA export factor 5. Tfb6 dissociates from TFIIH as a heterodimer with the Ssl2 subunit, a DNA helicase that drives promoter melting for the initiation of transcription. Tfb6 does not, however, dissociate Ssl2 from TFIIH in the context of a fully assembled transcripti...

  7. A Region of Bdp1 Necessary for Transcription Initiation That Is Located within the RNA Polymerase III Active Site Cleft

    OpenAIRE

    Hu, Hui-Lan; Wu, Chih-Chien; Lee, Jin-Cheng; Chen, Hung-Ta

    2015-01-01

    The RNA polymerase III (Pol III)-specific transcription factor Bdp1 is crucial to Pol III recruitment and promoter opening in transcription initiation, yet structural information is sparse. To examine its protein-binding targets within the preinitiation complex at the residue level, photoreactive amino acids were introduced into Saccharomyces cerevisiae Bdp1. Mutations within the highly conserved SANT domain cross-linked to the transcription factor IIB (TFIIB)-related transcription factor Brf...

  8. Regulation of Axillary Meristem Initiation by Transcription Factors and Plant Hormones.

    Science.gov (United States)

    Yang, Minglei; Jiao, Yuling

    2016-01-01

    One distinctive feature of plant post-embryonic development is that plants can undergo reiterative growth and continuous organogenesis throughout their lifetimes. Axillary meristems (AMs) in leaf axils play a central role in this growth and differences in meristem initiation and development produce the diversity of plant architecture. Studies in the past 15 years have shown that several transcription factors (TFs) and phytohormones affect AM initiation. In this review, we highlight recent research using systems biology approaches to examine the regulatory hierarchies underlying AM initiation and the role of auxins and cytokinins in AM initiation and development. This research revealed a developmental mechanism in which phytohormone signals act with a gene regulatory network containing multiple TFs to contribute to the initiation of AMs. PMID:26925087

  9. Functional and Structural Organization of Brf, the TFIIB-Related Component of the RNA Polymerase III Transcription Initiation Complex

    OpenAIRE

    Kassavetis, George A.; Kumar, Ashok; Ramirez, Enrique; Geiduschek, E.Peter

    1998-01-01

    Brf is the TFIIB-related component of Saccharomyces cerevisiae RNA polymerase III transcription initiation factor IIIB (TFIIIB). An extensive set of Brf fragments has been examined for the abilities to assemble the TFIIIB-DNA complex and recruit RNA polymerase III to accurately initiate transcription. The principal TFIIIB-assembly function of Brf was found to be contributed by a C-proximal segment spanning amino acids 435 to 545, while the principal transcription-directing function was contri...

  10. Structure of the initiation-competent RNA polymerase I and its implication for transcription

    Science.gov (United States)

    Pilsl, Michael; Crucifix, Corinne; Papai, Gabor; Krupp, Ferdinand; Steinbauer, Robert; Griesenbeck, Joachim; Milkereit, Philipp; Tschochner, Herbert; Schultz, Patrick

    2016-07-01

    Eukaryotic RNA polymerase I (Pol I) is specialized in rRNA gene transcription synthesizing up to 60% of cellular RNA. High level rRNA production relies on efficient binding of initiation factors to the rRNA gene promoter and recruitment of Pol I complexes containing initiation factor Rrn3. Here, we determine the cryo-EM structure of the Pol I-Rrn3 complex at 7.5 Å resolution, and compare it with Rrn3-free monomeric and dimeric Pol I. We observe that Rrn3 contacts the Pol I A43/A14 stalk and subunits A190 and AC40, that association re-organizes the Rrn3 interaction interface, thereby preventing Pol I dimerization; and Rrn3-bound and monomeric Pol I differ from the dimeric enzyme in cleft opening, and localization of the A12.2 C-terminus in the active centre. Our findings thus support a dual role for Rrn3 in transcription initiation to stabilize a monomeric initiation competent Pol I and to drive pre-initiation complex formation.

  11. Structure of the initiation-competent RNA polymerase I and its implication for transcription

    Science.gov (United States)

    Pilsl, Michael; Crucifix, Corinne; Papai, Gabor; Krupp, Ferdinand; Steinbauer, Robert; Griesenbeck, Joachim; Milkereit, Philipp; Tschochner, Herbert; Schultz, Patrick

    2016-01-01

    Eukaryotic RNA polymerase I (Pol I) is specialized in rRNA gene transcription synthesizing up to 60% of cellular RNA. High level rRNA production relies on efficient binding of initiation factors to the rRNA gene promoter and recruitment of Pol I complexes containing initiation factor Rrn3. Here, we determine the cryo-EM structure of the Pol I-Rrn3 complex at 7.5 Å resolution, and compare it with Rrn3-free monomeric and dimeric Pol I. We observe that Rrn3 contacts the Pol I A43/A14 stalk and subunits A190 and AC40, that association re-organizes the Rrn3 interaction interface, thereby preventing Pol I dimerization; and Rrn3-bound and monomeric Pol I differ from the dimeric enzyme in cleft opening, and localization of the A12.2 C-terminus in the active centre. Our findings thus support a dual role for Rrn3 in transcription initiation to stabilize a monomeric initiation competent Pol I and to drive pre-initiation complex formation. PMID:27418187

  12. Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription.

    Science.gov (United States)

    Xu, Muyu; Gonzalez-Hurtado, Elsie; Martinez, Ernest

    2016-04-01

    Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human β-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF-regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family.

  13. Dynamic competition between transcription initiation and repression: Role of nonequilibrium steps in cell-to-cell heterogeneity.

    Science.gov (United States)

    Mitarai, Namiko; Semsey, Szabolcs; Sneppen, Kim

    2015-08-01

    Transcriptional repression may cause transcriptional noise by a competition between repressor and RNA polymerase binding. Although promoter activity is often governed by a single limiting step, we argue here that the size of the noise strongly depends on whether this step is the initial equilibrium binding or one of the subsequent unidirectional steps. Overall, we show that nonequilibrium steps of transcription initiation systematically increase the cell-to-cell heterogeneity in bacterial populations. In particular, this allows also weak promoters to give substantial transcriptional noise. PMID:26382435

  14. The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF localization

    Directory of Open Access Journals (Sweden)

    Taft Ryan J

    2011-08-01

    Full Text Available Abstract Background Transcription initiation RNAs (tiRNAs are nuclear localized 18 nucleotide RNAs derived from sequences immediately downstream of RNA polymerase II (RNAPII transcription start sites. Previous reports have shown that tiRNAs are intimately correlated with gene expression, RNA polymerase II binding and behaviors, and epigenetic marks associated with transcription initiation, but not elongation. Results In the present work, we show that tiRNAs are commonly found at genomic CCCTC-binding factor (CTCF binding sites in human and mouse, and that CTCF sites that colocalize with RNAPII are highly enriched for tiRNAs. To directly investigate the relationship between tiRNAs and CTCF we examined tiRNAs originating near the intronic CTCF binding site in the human tumor suppressor gene, p21 (cyclin-dependent kinase inhibitor 1A gene, also known as CDKN1A. Inhibition of CTCF-proximal tiRNAs resulted in increased CTCF localization and increased p21 expression, while overexpression of CTCF-proximal tiRNA mimics decreased CTCF localization and p21 expression. We also found that tiRNA-regulated CTCF binding influences the levels of trimethylated H3K27 at the alternate upstream p21 promoter, and affects the levels of alternate p21 (p21alt transcripts. Extending these studies to another randomly selected locus with conserved CTCF binding we found that depletion of tiRNA alters nucleosome density proximal to sites of tiRNA biogenesis. Conclusions Taken together, these data suggest that tiRNAs modulate local epigenetic structure, which in turn regulates CTCF localization.

  15. Fate of HIV-1 cDNA intermediates during reverse transcription is dictated by transcription initiation site of virus genomic RNA

    Science.gov (United States)

    Masuda, Takao; Sato, Yoko; Huang, Yu-Lun; Koi, Satoshi; Takahata, Tatsuro; Hasegawa, Atsuhiko; Kawai, Gota; Kannagi, Mari

    2015-01-01

    Retroviral reverse transcription is accomplished by sequential strand-transfers of partial cDNA intermediates copied from viral genomic RNA. Here, we revealed an unprecedented role of 5′-end guanosine (G) of HIV-1 genomic RNA for reverse transcription. Based on current consensus for HIV-1 transcription initiation site, HIV-1 transcripts possess a single G at 5′-ends (G1-form). However, we found that HIV-1 transcripts with additional Gs at 5′-ends (G2- and G3-forms) were abundantly expressed in infected cells by using alternative transcription initiation sites. The G2- and G3-forms were also detected in the virus particle, although the G1-form predominated. To address biological impact of the 5′-G number, we generated HIV clone DNA to express the G1-form exclusively by deleting the alternative initiation sites. Virus produced from the clone showed significantly higher strand-transfer of minus strong-stop cDNA (-sscDNA). The in vitro assay using synthetic HIV-1 RNAs revealed that the abortive forms of -sscDNA were abundantly generated from the G3-form RNA, but dramatically reduced from the G1-form. Moreover, the strand-transfer of -sscDNA from the G1-form was prominently stimulated by HIV-1 nucleocapsid. Taken together, our results demonstrated that the 5′-G number that corresponds to HIV-1 transcription initiation site was critical for successful strand-transfer of -sscDNA during reverse transcription. PMID:26631448

  16. Molecular cloning of cDNA encoding the small subunit of Drosophila transcription initiation factor TFIIF.

    OpenAIRE

    Gong, D W; Mortin, M A; Horikoshi, M; Nakatani, Y

    1995-01-01

    Transcription initiation factor TFIIF is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30). We report here the molecular cloning of a Drosophila cDNA encoding TFIIF beta. The cDNA clone contains an open-reading frame encoding a 277 amino acid polypeptide having a calculated molecular mass of 32,107 Da. Comparison of the deduced amino acid sequence with the corresponding sequences from vertebrates showed only 50% identity, with four...

  17. Assessment of Site Specific Mutational Effect on Transcription Initiation at Escherichia coli Promoter

    Directory of Open Access Journals (Sweden)

    S. Kannan

    2009-01-01

    extended promoter region also played a key role in regulation transcription initiation in JM109 strain of E. coli. Conclusion: The present study concluded that the site specific changed in the extended promoter regions, particularly the-17/-16 base pairs had greater influence in the transcription initiation in E. coli. Thus the promoter engineering study will definitely pave the way to do both, on or off the genetic switches in bacterial system according to our needs to produce high protein of interest or decrease or block the expression of a particular unwanted protein.

  18. Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Rach

    Full Text Available The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: "focused" promoters with transcription start sites (TSSs that occur in a narrowly defined genomic span and "dispersed" promoters with TSSs that are spread over a larger window. Previous studies have explored the presence of genomic features, such as CpG islands and sequence motifs, in these promoter classes, but virtually no studies have directly investigated the relationship with chromatin features. Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II. These differences extend to histone variants (H2A.Z and marks (H3K4 methylation, as well as insulator binding (such as CTCF, independent of the expression levels of affected genes. Notably, differences are conserved across mammals and flies, and they provide for a clearer separation of promoter architectures than the presence and absence of CpG islands or the occurrence of stalled RNA polymerase. Computational models support the stronger contribution of chromatin features to the definition of dispersed promoters compared to focused start sites. Our results show that promoter classes defined from 5' capped transcripts not only reflect differences in the initiation process at the core promoter but also are indicative of divergent transcriptional programs established within gene-proximal nucleosome organization.

  19. Human Mitochondrial Transcription Revisited: ONLY TFAM AND TFB2M ARE REQUIRED FOR TRANSCRIPTION OF THE MITOCHONDRIAL GENES IN VITRO*

    OpenAIRE

    Litonin, Dmitry; Sologub, Marina; Shi, Yonghong; Savkina, Maria; Anikin, Michael; Falkenberg, Maria; Gustafsson, Claes M.; Temiakov, Dmitry

    2010-01-01

    Human mitochondrial transcription is driven by a single subunit RNA polymerase and a set of basal transcription factors. The development of a recombinant in vitro transcription system has allowed for a detailed molecular characterization of the individual components and their contribution to transcription initiation. We found that TFAM and TFB2M act synergistically and increase transcription efficiency 100–200-fold as compared with RNA polymerase alone. Both the light-strand promoter (LSP) an...

  20. A structural model of the E. coli PhoB Dimer in the transcription initiation complex

    Directory of Open Access Journals (Sweden)

    Tung Chang-Shung

    2012-03-01

    Full Text Available Abstract Background There exist > 78,000 proteins and/or nucleic acids structures that were determined experimentally. Only a small portion of these structures corresponds to those of protein complexes. While homology modeling is able to exploit knowledge-based potentials of side-chain rotomers and backbone motifs to infer structures for new proteins, no such general method exists to extend our understanding of protein interaction motifs to novel protein complexes. Results We use a Motif Binding Geometries (MBG approach, to infer the structure of a protein complex from the database of complexes of homologous proteins taken from other contexts (such as the helix-turn-helix motif binding double stranded DNA, and demonstrate its utility on one of the more important regulatory complexes in biology, that of the RNA polymerase initiating transcription under conditions of phosphate starvation. The modeled PhoB/RNAP/σ-factor/DNA complex is stereo-chemically reasonable, has sufficient interfacial Solvent Excluded Surface Areas (SESAs to provide adequate binding strength, is physically meaningful for transcription regulation, and is consistent with a variety of known experimental constraints. Conclusions Based on a straightforward and easy to comprehend concept, "proteins and protein domains that fold similarly could interact similarly", a structural model of the PhoB dimer in the transcription initiation complex has been developed. This approach could be extended to enable structural modeling and prediction of other bio-molecular complexes. Just as models of individual proteins provide insight into molecular recognition, catalytic mechanism, and substrate specificity, models of protein complexes will provide understanding into the combinatorial rules of cellular regulation and signaling.

  1. Effects of single-base substitutions within the acanthamoeba castellanii rRNA promoter on transcription and on binding of transcription initiation factor and RNA polymerase I

    Energy Technology Data Exchange (ETDEWEB)

    Kownin, P.; Bateman, E.; Paule, M.R.

    1988-02-01

    Single-point mutations were introduced into the promoter region of the Acanthamoeba castellanii rRNA gene by chemical mutagen treatment of a single-stranded clone in vitro, followed by reverse transcription and cloning of the altered fragment. The promoter mutants were tested for transcription initiation factor (TIF) binding by a template commitment assay plus DNase I footprinting and for transcription by an in vitro runoff assay. Point mutations within the previously identified TIF interaction region (between -20 and -47, motifs A and B) indicated that TIF interacts most strongly with a sequence centered at -29 and less tightly with sequences upstream and downstream. Some alterations of the base sequence closer to the transcription start site (and outside the TIF-protected site) also significantly decrease specific RNA synthesis in vitro. These were within the region which is protected from DNAse I digestion by polymerase I, but these mutations did not detectably affect the binding of polymerase to the promoter.

  2. The initiation factor TFE and the elongation factor Spt4/5 compete for the RNAP clamp during transcription initiation and elongation.

    Science.gov (United States)

    Grohmann, Dina; Nagy, Julia; Chakraborty, Anirban; Klose, Daniel; Fielden, Daniel; Ebright, Richard H; Michaelis, Jens; Werner, Finn

    2011-07-22

    TFIIE and the archaeal homolog TFE enhance DNA strand separation of eukaryotic RNAPII and the archaeal RNAP during transcription initiation by an unknown mechanism. We have developed a fluorescently labeled recombinant M. jannaschii RNAP system to probe the archaeal transcription initiation complex, consisting of promoter DNA, TBP, TFB, TFE, and RNAP. We have localized the position of the TFE winged helix (WH) and Zinc ribbon (ZR) domains on the RNAP using single-molecule FRET. The interaction sites of the TFE WH domain and the transcription elongation factor Spt4/5 overlap, and both factors compete for RNAP binding. Binding of Spt4/5 to RNAP represses promoter-directed transcription in the absence of TFE, which alleviates this effect by displacing Spt4/5 from RNAP. During elongation, Spt4/5 can displace TFE from the RNAP elongation complex and stimulate processivity. Our results identify the RNAP "clamp" region as a regulatory hot spot for both transcription initiation and transcription elongation. PMID:21777815

  3. Direct ultrasensitive electrochemical biosensing of pathogenic DNA using homogeneous target-initiated transcription amplification

    Science.gov (United States)

    Yan, Yurong; Ding, Shijia; Zhao, Dan; Yuan, Rui; Zhang, Yuhong; Cheng, Wei

    2016-01-01

    Sensitive and specific methodologies for detection of pathogenic gene at the point-of-care are still urgent demands in rapid diagnosis of infectious diseases. This work develops a simple and pragmatic electrochemical biosensing strategy for ultrasensitive and specific detection of pathogenic nucleic acids directly by integrating homogeneous target-initiated transcription amplification (HTITA) with interfacial sensing process in single analysis system. The homogeneous recognition and specific binding of target DNA with the designed hairpin probe triggered circular primer extension reaction to form DNA double-strands which contained T7 RNA polymerase promoter and served as templates for in vitro transcription amplification. The HTITA protocol resulted in numerous single-stranded RNA products which could synchronously hybridized with the detection probes and immobilized capture probes for enzyme-amplified electrochemical detection on the biosensor surface. The proposed electrochemical biosensing strategy showed very high sensitivity and selectivity for target DNA with a dynamic response range from 1 fM to 100 pM. Using salmonella as a model, the established strategy was successfully applied to directly detect invA gene from genomic DNA extract. This proposed strategy presented a simple, pragmatic platform toward ultrasensitive nucleic acids detection and would become a versatile and powerful tool for point-of-care pathogen identification.

  4. Preferential use of RNA leader sequences during influenza A transcription initiation in vivo.

    Science.gov (United States)

    Geerts-Dimitriadou, Christina; Goldbach, Rob; Kormelink, Richard

    2011-01-01

    In vitro transcription initiation studies revealed a preference of influenza A virus for capped RNA leader sequences with base complementarity to the viral RNA template. Here, these results were verified during an influenza infection in MDCK cells. Alfalfa mosaic virus RNA3 leader sequences mutated in their base complementarity to the viral template, or the nucleotides 5' of potential base-pairing residues, were tested for their use either singly or in competition. These analyses revealed that influenza transcriptase is able to use leaders from an exogenous mRNA source with a preference for leaders harboring base complementarity to the 3'-ultimate residues of the viral template, as previously observed during in vitro studies. Internal priming at the 3'-penultimate residue, as well as "prime-and-realign" was observed. The finding that multiple base-pairing promotes cap donor selection in vivo, and the earlier observed competitiveness of such molecules in vitro, offers new possibilities for antiviral drug design. PMID:21030059

  5. Genome-wide transcriptional analysis of salinity stressed japonica and indica rice genotypes during panicle initiation stage

    Science.gov (United States)

    Rice yield is most sensitive to salinity imposed during panicle initiation stage. In this study, we have focused on physiological and transcriptional responses of four rice genotypes exposed to salinity stress during panicle initiation. The genotypes selected included a pair of indicas (IR63731 and ...

  6. [SWI/SNF Protein Complexes Participate in the Initiation and Elongation Stages of Drosophila hsp70 Gene Transcription].

    Science.gov (United States)

    Mazina, M Yu; Nikolenko, Yu V; Krasnov, A N; Vorobyeva, N E

    2016-02-01

    The participation of the SWI/SNF chromatin remodeling complex in the stimulation of the RNA polymerase II binding to gene promotors was demonstrated in all model eukaryotic organisms. It was shown eight years ago that the SWI/SNF complex influence on transcription is not limited to its role in initiation but also includes participation in elongation and alternative splicing. In the current work, we describe the subunit composition of the SWI/SNF complexes participating in initiation, preparing for the elongation and elongation of hsp70 gene transcription in Drosophila melanogaster. The data reveal the high mobility of the SWI/SNF complex composition during the hsp 70 gene transcription process. We suggest a model describing the process of sequential SWI/SNF complex formation during heat-shock induced transcription of the hsp 70 gene.

  7. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    Science.gov (United States)

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR. PMID:25010399

  8. Motion tracking to enable pre-surgical margin mapping in basal cell carcinoma using optical imaging modalities: initial feasibility study using optical coherence tomography

    Science.gov (United States)

    Duffy, M.; Richardson, T. J.; Craythorne, E.; Mallipeddi, R.; Coleman, A. J.

    2014-02-01

    A system has been developed to assess the feasibility of using motion tracking to enable pre-surgical margin mapping of basal cell carcinoma (BCC) in the clinic using optical coherence tomography (OCT). This system consists of a commercial OCT imaging system (the VivoSight 1500, MDL Ltd., Orpington, UK), which has been adapted to incorporate a webcam and a single-sensor electromagnetic positional tracking module (the Flock of Birds, Ascension Technology Corp, Vermont, USA). A supporting software interface has also been developed which allows positional data to be captured and projected onto a 2D dermoscopic image in real-time. Initial results using a stationary test phantom are encouraging, with maximum errors in the projected map in the order of 1-2mm. Initial clinical results were poor due to motion artefact, despite attempts to stabilise the patient. However, the authors present several suggested modifications that are expected to reduce the effects of motion artefact and improve the overall accuracy and clinical usability of the system.

  9. Promoter binding, initiation, and elongation by bacteriophage T7 RNA polymerase. A single-molecule view of the transcription cycle.

    Science.gov (United States)

    Skinner, Gary M; Baumann, Christoph G; Quinn, Diana M; Molloy, Justin E; Hoggett, James G

    2004-01-30

    A single-molecule transcription assay has been developed that allows, for the first time, the direct observation of promoter binding, initiation, and elongation by a single RNA polymerase (RNAP) molecule in real-time. To promote DNA binding and transcription initiation, a DNA molecule tethered between two optically trapped beads was held near a third immobile surface bead sparsely coated with RNAP. By driving the optical trap holding the upstream bead with a triangular oscillation while measuring the position of both trapped beads, we observed the onset of promoter binding, promoter escape (productive initiation), and processive elongation by individual RNAP molecules. After DNA template release, transcription re-initiation on the same DNA template is possible; thus, multiple enzymatic turnovers by an individual RNAP molecule can be observed. Using bacteriophage T7 RNAP, a commonly used RNAP paradigm, we observed the association and dissociation (k(off)= 2.9 s(-1)) of T7 RNAP and promoter DNA, the transition to the elongation mode (k(for) = 0.36 s(-1)), and the processive synthesis (k(pol) = 43 nt s(-1)) and release of a gene-length RNA transcript ( approximately 1200 nt). The transition from initiation to elongation is much longer than the mean lifetime of the binary T7 RNAP-promoter DNA complex (k(off) > k(for)), identifying a rate-limiting step between promoter DNA binding and promoter escape. PMID:14597619

  10. Transcription initiation by human RNA polymerase II visualized at single-molecule resolution

    OpenAIRE

    Revyakin, Andrey; Zhang, Zhengjian; Coleman, Robert A.; Li, Yan; Inouye, Carla; Lucas, Julian K.; Park, Sang-Ryul; Chu, Steven; Tjian, Robert

    2012-01-01

    RNA polymerase II (Pol II) transcription is an immensely complex process that involves a myriad of regulatory factors and elements. In a technical tour de force, Tjian and colleagues now define an in vitro reconstituted Pol II system to detect and quantify Pol II transcription at single-molecule resolution using fluorescence video-microscopy. The study provides valuable insight into transcription reinitiation and, significantly, paves the way for a new era of opportunities in investigating th...

  11. The archaeal TFIIE homologue facilitates transcription initiation by enhancing TATA-box recognition

    NARCIS (Netherlands)

    Bell, S.D.; Brinkman, A.B.; Oost, van der J.; Jackson, S.P.

    2001-01-01

    Transcription from many archaeal promoters can be reconstituted in vitro using recombinant TATA-box binding protein (TBP) and transcription factor B (TFB)—homologues of eukaryal TBP and TFIIB—together with purified RNA polymerase (RNAP). However, all archaeal genomes sequenced to date reveal the pre

  12. Structural and functional aspects of winged-helix domains at the core of transcription initiation complexes.

    Science.gov (United States)

    Teichmann, Martin; Dumay-Odelot, Hélène; Fribourg, Sébastien

    2012-01-01

    The winged helix (WH) domain is found in core components of transcription systems in eukaryotes and prokaryotes. It represents a sub-class of the helix-turn-helix motif. The WH domain participates in establishing protein-DNA and protein-protein-interactions. Here, we discuss possible explanations for the enrichment of this motif in transcription systems.

  13. Genome-wide Analysis Reveals Extensive Functional Interaction between DNA Replication Initiation and Transcription in the Genome of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Calvin Tiengwe

    2012-07-01

    Full Text Available Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion.

  14. DNA repair deficiencies associated with mutations in genes encoding subunits of transcription initiation factor TFIIH in yeast.

    OpenAIRE

    Sweder, K S; Chun, R; Mori, T; Hanawalt, P C

    1996-01-01

    Several proteins, including Rad3 and Rad25(Ssl2), are essential for nucleotide excision repair (NER) and function in the RNA polymerase II transcription initiation complex TFIIH. Mutations in genes encoding two other subunits of TFIIH, TFB1 and SSL1, result in UV sensitivity and have been shown to take part in NER in an in vitro system. However, a deficiency in global NER does not exclude the possibility that such repair-deficient mutants can perform transcription-coupled repair (TCR), as sho...

  15. Nuclear respiratory factor 1 mediates the transcription initiation of insulin-degrading enzyme in a TATA box-binding protein-independent manner.

    Directory of Open Access Journals (Sweden)

    Lang Zhang

    Full Text Available CpG island promoters often lack canonical core promoter elements such as the TATA box, and have dispersed transcription initiation sites. Despite the prevalence of CpG islands associated with mammalian genes, the mechanism of transcription initiation from CpG island promoters remains to be clarified. Here we investigate the mechanism of transcription initiation of the CpG island-associated gene, insulin-degrading enzyme (IDE. IDE is ubiquitously expressed, and has dispersed transcription initiation sites. The IDE core promoter locates within a 32-bp region, which contains three CGGCG repeats and a nuclear respiratory factor 1 (NRF-1 binding motif. Sequential mutation analysis indicates that the NRF-1 binding motif is critical for IDE transcription initiation. The NRF-1 binding motif is functional, because NRF-1 binds to this motif in vivo and this motif is required for the regulation of IDE promoter activity by NRF-1. Furthermore, the NRF-1 binding site in the IDE promoter is conserved among different species, and dominant negative NRF-1 represses endogenous IDE expression. Finally, TATA-box binding protein (TBP is not associated with the IDE promoter, and inactivation of TBP does not abolish IDE transcription, suggesting that TBP is not essential for IDE transcription initiation. Our studies indicate that NRF-1 mediates IDE transcription initiation in a TBP-independent manner, and provide insights into the potential mechanism of transcription initiation for other CpG island-associated genes.

  16. A membrane-tethered transcription factor ANAC089 negatively regulates floral initiation in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The plant-specific NAC (NAM, ATAF1/2,and CUC2) transcription factors have a regulatory function in developmental processes and stress responses. Notably a group of NAC members named NTLs (NTM1-Like) are membrane-tethered, ensuring plants rapidly respond to developmental changes and environmental stimuli. Our results indicated that ANAC089 was a membrane-tethered transcription factor and its truncated form was responsible for the physiological function in flowering time control.

  17. Characterization of S1 nuclease sensitive site at transcription initiation region of Attacus ricini rDNA

    Institute of Scientific and Technical Information of China (English)

    何明亮; 赵慕钧; 靳嘉瑞; 李载平

    1997-01-01

    A single-stranded S1 nuclease hypersensitive site which contains a d(AT)18 sequence structure locat-ed in the 5 -non transcription spacer of silkworm A . ricini ribosomal RNA gene has been reported[1] Using starved-refed silkworms, another S1 nuclease sensitive site was found existing in the rDNA chromatin, while under merely starving, this S1 sensitive site disappeared[2] . Recently this inducible S1 sensitive site has been further determined. It consists of a d(GT)10-d(AT)10 special DNA sequence at the transcription initiation region, and shows a behavior of ease in DNA-unwinding, indicating that S1 nuclease sensitive sites may have an important function in the regulation of rDNA transcription and replication.

  18. Mediator is an intrinsic component of the basal RNA polymerase II machinery in vivo.

    Science.gov (United States)

    Lacombe, Thierry; Poh, Siew Lay; Barbey, Régine; Kuras, Laurent

    2013-11-01

    Mediator is a prominent multisubunit coactivator that functions as a bridge between gene-specific activators and the basal RNA polymerase (Pol) II initiation machinery. Here, we study the poorly documented role of Mediator in basal, or activator-independent, transcription in vivo. We show that Mediator is still present at the promoter when the Pol II machinery is recruited in the absence of an activator, in this case through a direct fusion between a basal transcription factor and a heterologous DNA binding protein bound to the promoter. Moreover, transcription resulting from activator-independent recruitment of the Pol II machinery is impaired by inactivation of the essential Mediator subunit Med17 due to the loss of Pol II from the promoter. Our results strongly support that Mediator is an integral component of the minimal machinery essential in vivo for stable Pol II association with the promoter.

  19. The barley HvNAC6 transcription factor affects ABA accumulation and promotes basal resistance against powdery mildew

    DEFF Research Database (Denmark)

    Chen, Yan-Jun; Perera, Venura; Wagner, Michael;

    2013-01-01

    /dark rhythm of ABA levels which were, however, not influenced by Bgh inoculation. The expression of the two ABA biosynthetic genes HvNCED1 and HvNCED2 was compromised, and transcript levels of the ABA conjugating HvBG7 enzyme were elevated in the HvNAC6 RNAi lines, but this effect was not clearly associated...

  20. High-density transcriptional initiation signals underline genomic islands in bacteria.

    Directory of Open Access Journals (Sweden)

    Qianli Huang

    Full Text Available Genomic islands (GIs, frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of "alien" elements which probably undergo special temporal-spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these "exotic" regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased "non-optimal" codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for "alien" regions, but also provide hints to the special

  1. A transcript finishing initiative for closing gaps in the human transcriptome

    DEFF Research Database (Denmark)

    Sogayar, Mari Cleide; Camargo, Anamaria A; Bettoni, Fabiana;

    2004-01-01

    for experimental validation was designated a transcript finishing unit (TFU). A total of 489 TFUs were selected for validation, and an overall efficiency of 43.1% was achieved. We generated a total of 59,975 bp of transcribed sequences organized into 432 exons, contributing to the definition of the structure...... databases, and the structure of 69.2% of these TFUs was not correctly predicted by computer programs. The TF strategy provides a significant contribution to the definition of the complete catalog of human genes and transcripts, because it appears to be particularly useful for identification of low abundance...

  2. Transcription of ribosomal RNA genes is initiated in the third cell cycle of bovine embryos

    DEFF Research Database (Denmark)

    Jakobsen, Anne Sørig; Avery, Birthe; Dieleman, Steph J.;

    2006-01-01

    of the embryonic genome. In the present study, ribosomal RNA (rRNA) transcription was investigated by visualization of the rRNA by fluorescent in situ hybridization, and subsequent visualization of the argyrophilic nucleolar proteins by silver staining. A total of 145 in vivo developed and 200 in vitro produced...

  3. Pulmonary Metastasis of Basal Cell Carcinoma

    OpenAIRE

    Seo, Sang-Hee; Shim, Woo-Haing; SHIN, DONG-HOON; Kim, Yun-Seong; Sung, Hyun-Woo

    2011-01-01

    Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes. Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and management. We describe the case of a patient with a metastatic basal cell carcinoma present in the lungs. The differential diagnosis of suspected metastatic lesions should include metastases from a cutaneous basal cell carcinoma, in addition to those from more commonly metastasizing carcinomas, especially in patients with a histor...

  4. Elevated SP-1 transcription factor expression and activity drives basal and hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small cell lung cancer.

    Science.gov (United States)

    Deacon, Karl; Onion, David; Kumari, Rajendra; Watson, Susan A; Knox, Alan J

    2012-11-16

    VEGF plays a central role in angiogenesis in cancer. Non-small cell lung cancer (NSCLC) tumors have increased microvascular density, localized hypoxia, and high VEGF expression levels; however, there is a lack of understanding of how oncogenic and tumor microenvironment changes such as hypoxia lead to greater VEGF expression in lung and other cancers. We show that NSCLC cells secreted higher levels of VEGF than normal airway epithelial cells. Actinomycin D inhibited all NSCLC VEGF secretion, and VEGF minimal promoter-luciferase reporter constructs were constitutively active until the last 85 base pairs before the transcription start site containing three SP-1 transcription factor-binding sites; mutation of these VEGF promoter SP-1-binding sites eliminated VEGF promoter activity. Furthermore, dominant negative SP-1, mithramycin A, and SP-1 shRNA decreased VEGF promoter activity, whereas overexpression of SP-1 increased VEGF promoter activity. Chromatin immunoprecipitation assays demonstrated SP-1, p300, and PCA/F histone acetyltransferase binding and histone H4 hyperacetylation at the VEGF promoter in NSCLC cells. Cultured NSCLC cells expressed higher levels of SP-1 protein than normal airway epithelial cells, and double-fluorescence immunohistochemistry showed a strong correlation between SP-1 and VEGF in human NSCLC tumors. In addition, hypoxia-driven VEGF expression in NSCLC cells was SP-1-dependent, with hypoxia increasing SP-1 activity and binding to the VEGF promoter. These studies are the first to demonstrate that overexpression of SP-1 plays a central role in hypoxia-induced VEGF secretion. PMID:22992725

  5. Transcriptional profiling of the murine cutaneous response during initial and subsequent infestations with Ixodes scapularis nymphs

    Directory of Open Access Journals (Sweden)

    Heinze Dar M

    2012-02-01

    Full Text Available Abstract Background Ixodes scapularis ticks are hematophagous arthropods capable of transmitting many infectious agents to humans. The process of blood feeding is an extended and continuous interplay between tick and host responses. While this process has been studied extensively in vitro, no global understanding of the host response to ticks has emerged. Methods To address this issue, we used PCR-arrays to measure skin-specific expression of 233 discrete genes at 8 time points during primary and secondary infestations of mice with pathogen-free I. scapularis nymphs. Selected results were then validated at the mRNA and protein levels by additional real-time PCR and bioplex assay. Results Primary infestation was characterized by the late induction of an innate immune response. Lectin pattern recognition receptors, cytokines, and chemokines were upregulated consistent with increased neutrophil and macrophage migration. Gene ontology and pathway analyses of downregulated genes suggested inhibition of gene transcription and Th17 immunity. During the secondary infestation, additional genes were modulated suggesting a broader involvement of immune cells including CD8 and CD4 positive T lymphocytes. The cytokine response showed a mixed Th1/Th2 profile with a potential for T regulatory cell activity. Key gene ontology clusters observed during the secondary infestation were cell migration and activation. Matrix metalloproteinases were upregulated, apoptosis-related genes were differentially modulated, and immunoreceptor signaling molecules were upregulated. In contrast, transcripts related to mitogenic, WNT, Hedgehog, and stress pathways were downregulated. Conclusions Our results support a model of tick feeding where lectin pattern recognition receptors orchestrate an innate inflammatory response during primary infestation that primes a mixed Th1/Th2 response upon secondary exposure. Tick feeding inhibits gene transcription and Th17 immunity. Salivary

  6. Basal Cell Carcinoma (BCC)

    Science.gov (United States)

    ... epithelioma, is the most common form of skin cancer. Basal cell carcinoma usually occurs on sun-damaged skin, especially ... other health issues. Infiltrating or morpheaform basal cell carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive ...

  7. In Vitro Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA

    OpenAIRE

    Smith, Janet L.; Grossman, Alan D.

    2015-01-01

    DnaA, the replication initiation protein in bacteria, is an AAA+ ATPase that binds and hydrolyzes ATP and exists in a heterogeneous population of ATP-DnaA and ADP-DnaA. DnaA binds cooperatively to the origin of replication and several other chromosomal regions, and functions as a transcription factor at some of these regions. We determined the binding properties of Bacillus subtilis DnaA to genomic DNA in vitro at single nucleotide resolution using in vitro DNA affinity purification and deep ...

  8. Determining physical constraints in transcriptional initiation complexes using DNA sequence analysis.

    Directory of Open Access Journals (Sweden)

    Ryan K Shultzaberger

    Full Text Available Eukaryotic gene expression is often under the control of cooperatively acting transcription factors whose binding is limited by structural constraints. By determining these structural constraints, we can understand the "rules" that define functional cooperativity. Conversely, by understanding the rules of binding, we can infer structural characteristics. We have developed an information theory based method for approximating the physical limitations of cooperative interactions by comparing sequence analysis to microarray expression data. When applied to the coordinated binding of the sulfur amino acid regulatory protein Met4 by Cbf1 and Met31, we were able to create a combinatorial model that can correctly identify Met4 regulated genes. Interestingly, we found that the major determinant of Met4 regulation was the sum of the strength of the Cbf1 and Met31 binding sites and that the energetic costs associated with spacing appeared to be minimal.

  9. Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!

    Directory of Open Access Journals (Sweden)

    Christopher E Pearson

    2011-03-01

    Full Text Available Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU, to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG•(CTG DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins, yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent

  10. Transcription Factors and Medium Suitable for Initiating the Differentiation of Human-Induced Pluripotent Stem Cells to the Hepatocyte Lineage.

    Science.gov (United States)

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-09-01

    Transcription factors and culture media were investigated to determine the condition to initiate the differentiation of human-induced pluripotent stem (iPS) cells most efficiently. The expression of genes in human adult liver was compared with that in 201B7 cells (iPS cells) using cDNA microarray analysis. Episomal plasmids expressing transcription factors were constructed. 201B7 cells were transfected with the episomal plasmids and cultured in ReproFF (feeder-free media maintaining pluripotency), Leibovitz-15 (L15), William's E (WE), or Dulbecco's modified Eagle medium/Nutrient F-12 Ham (DF12) for 7 days. RNA was isolated and subjected to real-time quantitative PCR to analyze the expression of alpha-feto protein (AFP) and albumin. cDNA microarray analysis revealed 16 transcription factors that were upregulated in human adult liver relative to that in 201B7 cells. Episomal plasmids expressing these 16 genes were transfected into 201B7 cells. CCAAT/enhancer-binding protein alpha (CEBPA), CCAAT/enhancer-binding protein beta (CEBPB), forkhead box A1 (FOXA1), and forkhead box A3 (FOXA3) up-regulated AFP and down-regulated Nanog. These four genes were further analyzed. The expression of AFP and albumin was the highest in 201B7 cells transfected with the combination of CEBPA, CEBPB, FOXA1, and FOXA3 and cultured in WE. The combination of CEBPA, CEBPB, FOXA1, and FOXA3 was suitable for 201B7 cells to initiate differentiation to the hepatocyte lineage and WE was the most suitable medium for culture after transfection. J. Cell. Biochem. 117: 2001-2009, 2016. © 2016 Wiley Periodicals, Inc. PMID:26773721

  11. Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor.

    Science.gov (United States)

    Goh, Tatsuaki; Toyokura, Koichi; Wells, Darren M; Swarup, Kamal; Yamamoto, Mayuko; Mimura, Tetsuro; Weijers, Dolf; Fukaki, Hidehiro; Laplaze, Laurent; Bennett, Malcolm J; Guyomarc'h, Soazig

    2016-09-15

    Lateral root formation is an important determinant of root system architecture. In Arabidopsis, lateral roots originate from pericycle cells, which undergo a program of morphogenesis to generate a new lateral root meristem. Despite its importance for root meristem organization, the onset of quiescent center (QC) formation during lateral root morphogenesis remains unclear. Here, we used live 3D confocal imaging to monitor cell organization and identity acquisition during lateral root development. Our dynamic observations revealed an early morphogenesis phase and a late meristem formation phase as proposed in the bi-phasic growth model. Establishment of lateral root QCs coincided with this developmental phase transition. QC precursor cells originated from the outer layer of stage II lateral root primordia, within which the SCARECROW (SCR) transcription factor was specifically expressed. Disrupting SCR function abolished periclinal divisions in this lateral root primordia cell layer and perturbed the formation of QC precursor cells. We conclude that de novo QC establishment in lateral root primordia operates via SCR-mediated formative cell division and coincides with the developmental phase transition. PMID:27510971

  12. Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

    Directory of Open Access Journals (Sweden)

    Miller Eric S

    2010-12-01

    Full Text Available Abstract Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit; and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context.

  13. YabA of Bacillus subtilis controls DnaA-mediated replication initiation but not the transcriptional response to replication stress

    OpenAIRE

    Goranov, Alexi I.; Breier, Adam M.; Merrikh, Houra; Grossman, Alan D.

    2009-01-01

    yabA encodes a negative regulator of replication initiation in Bacillus subtilis and homologues are found in many other Gram-positive species. YabA interacts with the β-processivity clamp (DnaN) of DNA polymerase and with the replication initiator and transcription factor DnaA. Because of these interactions, YabA has been proposed to modulate the activity of DnaA. We investigated the role of YabA in regulating replication initiation and the activity of DnaA as a transcription factor. We foun...

  14. Post-transcriptional Boolean computation by combining aptazymes controlling mRNA translation initiation and tRNA activation.

    Science.gov (United States)

    Klauser, Benedikt; Saragliadis, Athanasios; Ausländer, Simon; Wieland, Markus; Berthold, Michael R; Hartig, Jörg S

    2012-09-01

    In cellular systems environmental and metabolic signals are integrated for the conditional control of gene expression. On the other hand, artificial manipulation of gene expression is of high interest for metabolic and genetic engineering. Especially the reprogramming of gene expression patterns to orchestrate cellular responses in a predictable fashion is considered to be of great importance. Here we introduce a highly modular RNA-based system for performing Boolean logic computation at a post-transcriptional level in Escherichia coli. We have previously shown that artificial riboswitches can be constructed by utilizing ligand-dependent Hammerhead ribozymes (aptazymes). Employing RNA self-cleavage as the expression platform-mechanism of an artificial riboswitch has the advantage that it can be applied to control several classes of RNAs such as mRNAs, tRNAs, and rRNAs. Due to the highly modular and orthogonal nature of these switches it is possible to combine aptazyme regulation of activating a suppressor tRNA with the regulation of mRNA translation initiation. The different RNA classes can be controlled individually by using distinct aptamers for individual RNA switches. Boolean logic devices are assembled by combining such switches in order to act on the expression of a single mRNA. In order to demonstrate the high modularity, a series of two-input Boolean logic operators were constructed. For this purpose, we expanded our aptazyme toolbox with switches comprising novel behaviours with respect to the small molecule triggers thiamine pyrophosphate (TPP) and theophylline. Then, individual switches were combined to yield AND, NOR, and ANDNOT gates. This study demonstrates that post-transcriptional aptazyme-based switches represent versatile tools for engineering advanced genetic devices and circuits without the need for regulatory protein cofactors. PMID:22777205

  15. GlnR negatively regulates the transcription of the alanine dehydrogenase encoding gene ald in Amycolatopsis mediterranei U32 under nitrogen limited conditions via specific binding to its major transcription initiation site.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available Ammonium assimilation is catalyzed by two enzymatic pathways, i.e., glutamine synthetase/glutamate synthase (GS/GOGAT and alanine dehydrogenase (AlaDH in Amycolatopsis mediterranei U32. Under nitrogen-rich conditions, the AlaDH pathway is the major route for ammonium assimilation, while the GS/GOGAT pathway takes over when the extracellular nitrogen supply is limited. The global nitrogen regulator GlnR was previously characterized to activate the transcription of the GS encoding gene glnA in response to nitrogen limitation and is demonstrated in this study as a repressor for the transcription of the AlaDH encoding gene ald, whose regulation is consistent with the switch of the ammonium assimilation pathways from AlaDH to GS/GOGAT responding to nitrogen limitation. Three transcription initiation sites (TISs of ald were determined with primer extension assay, among which transcription from aldP2 contributed the major transcripts under nitrogen-rich conditions but was repressed to an undetectable level in response to nitrogen limitation. Through DNase I footprinting assay, two separate regions were found to be protected by GlnR within ald promoter, within which three GlnR binding sites (a1, b1 sites in region I and a2 site in region II were defined. Interestingly, the major TIS aldP2 is located in the middle of a2 site within region II. Therefore, one may easily conclude that GlnR represses the transcription of ald via specific binding to the GlnR binding sites, which obviously blocks the transcription initiation from aldP2 and therefore reduces ald transcripts.

  16. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

    Science.gov (United States)

    Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

    2016-01-01

    The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

  17. Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo.

    Science.gov (United States)

    Uprety, Bhawana; Sen, Rwik; Bhaumik, Sukesh R

    2015-09-01

    NuA4 (nucleosome acetyltransferase of H4) promotes transcriptional initiation of TFIID (a complex of TBP and TBP-associated factors [TAFs])-dependent ribosomal protein genes involved in ribosome biogenesis. However, it is not clearly understood how NuA4 regulates the transcription of ribosomal protein genes. Here, we show that NuA4 is recruited to the promoters of ribosomal protein genes, such as RPS5, RPL2B, and RPS11B, for TFIID recruitment to initiate transcription, and the recruitment of NuA4 to these promoters is impaired in the absence of its Eaf1p component. Intriguingly, impaired NuA4 recruitment in a Δeaf1 strain depletes recruitment of TFIID (a TAF-dependent form of TBP) but not the TAF-independent form of TBP to the promoters of ribosomal protein genes. However, in the absence of NuA4, SAGA (Spt-Ada-Gcn5-acetyltransferase) is involved in targeting the TAF-independent form of TBP to the promoters of ribosomal protein genes for transcriptional initiation. Thus, NuA4 plays an important role in targeting TFIID to the promoters of ribosomal protein genes for transcriptional initiation in vivo. Such a function is mediated via its targeted histone acetyltransferase activity. In the absence of NuA4, ribosomal protein genes lose TFIID dependency and become SAGA dependent for transcriptional initiation. Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions.

  18. Identification of EhTIF-IA: The putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA.

    Science.gov (United States)

    Srivastava, Ankita; Bhattacharya, Alok; Bhattacharya, Sudha; Jhingan, Gagan Deep

    2016-03-01

    Initiation of rDNA transcription requires the assembly of a specific multi-protein complex at the rDNA promoter containing the RNA Pol I with auxiliary factors. One of these factors is known as Rrn3P in yeast and Transcription Initiation Factor IA (TIF-IA) in mammals. Rrn3p/TIF-IA serves as a bridge between RNA Pol I and the pre-initiation complex at the promoter. It is phosphorylated at multiple sites and is involved in regulation of rDNA transcription in a growth-dependent manner. In the early branching parasitic protist Entamoeba histolytica, the rRNA genes are present exclusively on circular extra chromosomal plasmids. The protein factors involved in regulation of rDNA transcription in E. histolytica are not known. We have identified the E. histolytica equivalent of TIF-1A (EhTIF-IA) by homology search within the database and was further cloned and expressed. Immuno-localization studies showed that EhTIF-IA co-localized partially with fibrillarin in the peripherally localized nucleolus. EhTIF-IA was shown to interact with the RNA Pol I-specific subunit RPA12 both in vivo and in vitro. Mass spectroscopy data identified RNA Pol I-specific subunits and other nucleolar proteins to be the interacting partners of EhTIF-IA. Our study demonstrates for the first time a conserved putative RNA Pol I transcription factor TIF-IA in E. histolytica. PMID:26949087

  19. Identification of EhTIF-IA: The putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA.

    Science.gov (United States)

    Srivastava, Ankita; Bhattacharya, Alok; Bhattacharya, Sudha; Jhingan, Gagan Deep

    2016-03-01

    Initiation of rDNA transcription requires the assembly of a specific multi-protein complex at the rDNA promoter containing the RNA Pol I with auxiliary factors. One of these factors is known as Rrn3P in yeast and Transcription Initiation Factor IA (TIF-IA) in mammals. Rrn3p/TIF-IA serves as a bridge between RNA Pol I and the pre-initiation complex at the promoter. It is phosphorylated at multiple sites and is involved in regulation of rDNA transcription in a growth-dependent manner. In the early branching parasitic protist Entamoeba histolytica, the rRNA genes are present exclusively on circular extra chromosomal plasmids. The protein factors involved in regulation of rDNA transcription in E. histolytica are not known. We have identified the E. histolytica equivalent of TIF-1A (EhTIF-IA) by homology search within the database and was further cloned and expressed. Immuno-localization studies showed that EhTIF-IA co-localized partially with fibrillarin in the peripherally localized nucleolus. EhTIF-IA was shown to interact with the RNA Pol I-specific subunit RPA12 both in vivo and in vitro. Mass spectroscopy data identified RNA Pol I-specific subunits and other nucleolar proteins to be the interacting partners of EhTIF-IA. Our study demonstrates for the first time a conserved putative RNA Pol I transcription factor TIF-IA in E. histolytica.

  20. Identification of EhTIF-IA: The putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA

    Indian Academy of Sciences (India)

    Ankita Srivastava; Alok Bhattacharya; Sudha Bhattacharya; Gagan Deep Jhingan

    2016-03-01

    Initiation of rDNA transcription requires the assembly of a specific multi-protein complex at the rDNA promoter containing the RNA Pol I with auxiliary factors. One of these factors is known as Rrn3P in yeast and Transcription Initiation Factor IA (TIF-IA) in mammals. Rrn3p/TIF-IA serves as a bridge between RNA Pol I and the pre-initiation complex at the promoter. It is phosphorylated at multiple sites and is involved in regulation of rDNA transcription in a growth-dependent manner. In the early branching parasitic protist Entamoeba histolytica, the rRNA genes are present exclusively on circular extra chromosomal plasmids. The protein factors involved in regulation of rDNA transcription in E. histolytica are not known. We have identified the E. histolytica equivalent of TIF-1A (EhTIF-IA) by homology search within the database and was further cloned and expressed. Immuno-localization studies showed that EhTIF-IA co-localized partially with fibrillarin in the peripherally localized nucleolus. EhTIF-IA was shown to interact with the RNA Pol I-specific subunit RPA12 both in vivo and in vitro. Mass spectroscopy data identified RNA Pol I-specific subunits and other nucleolar proteins to be the interacting partners of EhTIF-IA. Our study demonstrates for the first time a conserved putative RNA Pol I transcription factor TIF-IA in E. histolytica.

  1. Events during eucaryotic rRNA transcription initiation and elongation: Conversion from the closed to the open promoter complex requires nucleotide substrates

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, E.; Paule, M.R.

    1988-05-01

    Chemical footprinting and topological analysis were carried out on the Acanthamoeba castellanii rRNA transcription initiation factor (TIF) and RNA polymerase I complexes with DNA during transcription initiation and elongation. The results show that the binding of TIF and polymerase to the promoter does not alter the supercoiling of the DNA template and the template does not become sensitive to modification by diethylpyro-carbonate, which can identify melted DNA regions. Thus, in contrast to bacterial RNA polymerase, the eucaryotic RNA polymerase I-promoter complex is in a closed configuration preceding addition of nucleotides in vitro. Initiation and 3'-O-methyl CTP-limited translocation by RNA polymerase I results in separation of the polymerase-TIF footprints, leaving the TIF footprint unaltered. In contrast, initiation and translocation result in a significant change in the conformation of the polymerase-DNA complex, culminating in an unwound DNA region of at least 10 base pairs.

  2. Nevoid Basal Cell Carcinoma Syndrome

    Science.gov (United States)

    ... Nevoid Basal Cell Carcinoma Syndrome Request Permissions Nevoid Basal Cell Carcinoma Syndrome Approved by the Cancer.Net Editorial Board , 04/2016 What is Nevoid Basal Cell Carcinoma Syndrome? Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is ...

  3. In Vitro Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA.

    Directory of Open Access Journals (Sweden)

    Janet L Smith

    2015-05-01

    Full Text Available DnaA, the replication initiation protein in bacteria, is an AAA+ ATPase that binds and hydrolyzes ATP and exists in a heterogeneous population of ATP-DnaA and ADP-DnaA. DnaA binds cooperatively to the origin of replication and several other chromosomal regions, and functions as a transcription factor at some of these regions. We determined the binding properties of Bacillus subtilis DnaA to genomic DNA in vitro at single nucleotide resolution using in vitro DNA affinity purification and deep sequencing (IDAP-Seq. We used these data to identify 269 binding regions, refine the consensus sequence of the DnaA binding site, and compare the relative affinity of binding regions for ATP-DnaA and ADP-DnaA. Most sites had a slightly higher affinity for ATP-DnaA than ADP-DnaA, but a few had a strong preference for binding ATP-DnaA. Of the 269 sites, only the eight strongest binding ones have been observed to bind DnaA in vivo, suggesting that other cellular factors or the amount of available DnaA in vivo restricts DnaA binding to these additional sites. Conversely, we found several chromosomal regions that were bound by DnaA in vivo but not in vitro, and that the nucleoid-associated protein Rok was required for binding in vivo. Our in vitro characterization of the inherent ability of DnaA to bind the genome at single nucleotide resolution provides a backdrop for interpreting data on in vivo binding and regulation of DnaA, and is an approach that should be adaptable to many other DNA binding proteins.

  4. Structure of the transcription initiation and termination sequences of seven early genes in the vaccinia virus HindIII D fragment.

    Science.gov (United States)

    Lee-Chen, G J; Bourgeois, N; Davidson, K; Condit, R C; Niles, E G

    1988-03-01

    The vaccinia virus HindIII D fragment is 16,060 bp in length and encodes 13 complete genes [E.G. Niles et al. (1986). Virology 153, 96-112; S. L. Weinrich and D. E. Hruby (1986). Nucleic Acids Res. 14, 3003-3016]. Six of these genes are expressed only at early times after infection and one gene is expressed at both early and late times [G. -J. Lee-Chen and E. G. Niles (1988). Virology 163, 52-63]. Transcript mapping by S1 nuclease protection studies was carried out and compared to the results of primer extension analyses, in order to locate map positions of the 5' termini of each early mRNA. The lengths of the products of in vitro transcription, from DNA templates which possess the transcription start regions of each of the early genes, were determined and compared to the lengths of DNA products generated by S1 nuclease protection and primer extension, in order to demonstrate that the 5' termini identified by S1 mapping and primer extension are due to transcription initiation and not to mRNA processing. For each of the early genes in the HindIII D fragment, transcription starts within 25 nucleotides of the translation initiation codon. The precise location of the 3' termini of each early transcript was identified by S1 nuclease mapping. In all but one case, the 3' ends map within 75 nucleotides of the putative transcription termination signal TTTTTNT [G. Rohrmann, L. Yuen, and B. Moss (1986).

  5. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  6. Dynamic Association of the Replication Initiator and Transcription Factor DnaA with the Bacillus subtilis Chromosome during Replication Stress ▿

    OpenAIRE

    Breier, Adam M.; Grossman, Alan D.

    2008-01-01

    DnaA functions as both a transcription factor and the replication initiator in bacteria. We characterized the DNA binding dynamics of DnaA on a genomic level. Based on cross-linking and chromatin immunoprecipitation data, DnaA binds at least 17 loci, 15 of which are regulated transcriptionally in response to inhibition of replication (replication stress). Six loci, each of which has a cluster of at least nine potential DnaA binding sites, had significant increases in binding by DnaA when repl...

  7. Regulation of transcription attenuation and translation initiation by allosteric control of an RNA-binding protein: the Bacillus subtilis TRAP protein.

    Science.gov (United States)

    Babitzke, Paul

    2004-04-01

    Tryptophan allosterically controls the 11-subunit trp RNA-binding attenuation protein (TRAP) of Bacillus subtilis. When activated by tryptophan, TRAP binds to multiple trinucleotide repeats in target transcripts. TRAP is responsible for the decision to terminate transcription in the leader region of the trpEDCFBA operon or to allow transcription to proceed into the structural genes. TRAP also regulates translation of trpE by promoting formation of an RNA structure that prevents ribosome binding. In addition, bound TRAP regulates translation initiation of pabA, trpP and ycbK by directly blocking ribosome binding. The anti-TRAP protein inhibits TRAP activity by competing with RNA for the RNA binding surface of TRAP. PMID:15063849

  8. A NF-κB-dependent dual promoter-enhancer initiates the lipopolysaccharide-mediated transcriptional activation of the chicken lysozyme in macrophages.

    Science.gov (United States)

    Witham, James; Ouboussad, Lylia; Lefevre, Pascal F

    2013-01-01

    The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor (CTCF) from a negative regulatory element upstream of the lysozyme transcription start site. LINoCR is transcribed from a promoter originally characterized as a hormone response enhancer in the oviduct. Herein, we report the characterization of this cis-regulatory element (CRE). In activated macrophages, a 60 bp region bound by NF-κB, AP1 and C/EBPβ controls this CRE, which is strictly dependent on NF-κB binding for its activity in luciferase assays. Moreover, the serine/threonine kinase IKKα, known to be recruited by NF-κB to NF-κB-dependent genes is found at the CRE and within the transcribing regions of both cLys and LINoCR. Such repartition suggests a simultaneous promoter and enhancer activity of this CRE, initiating cLys transcriptional activation and driving CTCF eviction. This recruitment was transient despite persistence of both cLys transcription and NF-κB binding to the CRE. Finally, comparing cLys with other LPS-inducible genes indicates that IKKα detection within transcribing regions can be correlated with the presence of the elongating form of RNA polymerase II or concentrated in the 3' end of the gene.

  9. The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor.

    NARCIS (Netherlands)

    G. Weeda (Geert); M. Rossignol; R.A. Fraser; G.S. Winkler (Sebastiaan); W. Vermeulen (Wim); L.J. van 't Veer (Laura); L. Ma (Libin); J.H.J. Hoeijmakers (Jan); J-M. Egly (Jean-Marc)

    1997-01-01

    textabstractMutations in the basal transcription initiation/DNA repair factor TFIIH are responsible for three human disorders: xeroderma pigmentosum (XP), cockayne syndrome (CS) and trichothiodystrophy (TTD). The non-repair features of CS and TTD are thought to be due to a partial inactivation of th

  10. ppGpp Binding to a Site at the RNAP-DksA Interface Accounts for Its Dramatic Effects on Transcription Initiation during the Stringent Response.

    Science.gov (United States)

    Ross, Wilma; Sanchez-Vazquez, Patricia; Chen, Albert Y; Lee, Jeong-Hyun; Burgos, Hector L; Gourse, Richard L

    2016-06-16

    Throughout the bacterial domain, the alarmone ppGpp dramatically reprograms transcription following nutrient limitation. This "stringent response" is critical for survival and antibiotic tolerance and is a model for transcriptional regulation by small ligands. We report that ppGpp binds to two distinct sites 60 Å apart on E. coli RNA polymerase (RNAP), one characterized previously (site 1) and a second identified here at an interface of RNAP and the transcription factor DksA (site 2). The location and unusual tripartite nature of site 2 account for the DksA-ppGpp synergism and suggest mechanisms for ppGpp enhancement of DksA's effects on RNAP. Site 2 binding results in the majority of ppGpp's effects on transcription initiation in vitro and in vivo, and strains lacking site 2 are severely impaired for growth following nutritional shifts. Filling of the two sites at different ppGpp concentrations would expand the dynamic range of cellular responses to changes in ppGpp levels. PMID:27237053

  11. Myeloidcell—lineage and premylocytic—stage—specific—expression of the mouse myeloperoxidase gene is controlled at initiation as well as elongation levels of transcription

    Institute of Scientific and Technical Information of China (English)

    ZHUJINGDE

    1999-01-01

    The myeloperoxidase (MPO) is an important microbicidal protein present at high concentration in the primary granule of mature granulocyte and its expression is regulated in both myeloidcell-lineage and premyelocytic-stagespecific manners.A better understanding of the underlying control mechanisms should provide insights into the temporal and co-ordinate regulation of the gene expression during granulopoiesis.We have identified its promoter by mapping the start(s) of transcription using various molecular approaches together with demonstrating the promoter function of the relevant DNA segment in a transient transfection reporter assay.Besides the major start of transcription mapped at G residue,11 nucleotide upstream of the 3' end of exon 0,the usage of that is specific to the MPO expressing cell lines,we have shown that irrespective of the MPO-expression status of the hematopoietic cells,transcription occurs broadly within a two kb region upstream of the 5' proximity of the gene,and is largely terminated in intron 2.These data support a model of the premyelocytic-stage-specific MPO expression,the control of which is operated at initiation as well as elongation levels of transcription.

  12. ppGpp Binding to a Site at the RNAP-DksA Interface Accounts for Its Dramatic Effects on Transcription Initiation during the Stringent Response.

    Science.gov (United States)

    Ross, Wilma; Sanchez-Vazquez, Patricia; Chen, Albert Y; Lee, Jeong-Hyun; Burgos, Hector L; Gourse, Richard L

    2016-06-16

    Throughout the bacterial domain, the alarmone ppGpp dramatically reprograms transcription following nutrient limitation. This "stringent response" is critical for survival and antibiotic tolerance and is a model for transcriptional regulation by small ligands. We report that ppGpp binds to two distinct sites 60 Å apart on E. coli RNA polymerase (RNAP), one characterized previously (site 1) and a second identified here at an interface of RNAP and the transcription factor DksA (site 2). The location and unusual tripartite nature of site 2 account for the DksA-ppGpp synergism and suggest mechanisms for ppGpp enhancement of DksA's effects on RNAP. Site 2 binding results in the majority of ppGpp's effects on transcription initiation in vitro and in vivo, and strains lacking site 2 are severely impaired for growth following nutritional shifts. Filling of the two sites at different ppGpp concentrations would expand the dynamic range of cellular responses to changes in ppGpp levels.

  13. Low probability of initiating nirS transcription explains observed gas kinetics and growth of bacteria switching from aerobic respiration to denitrification.

    Directory of Open Access Journals (Sweden)

    Junaid Hassan

    2014-11-01

    Full Text Available In response to impending anoxic conditions, denitrifying bacteria sustain respiratory metabolism by producing enzymes for reducing nitrogen oxyanions/-oxides (NOx to N2 (denitrification. Since denitrifying bacteria are non-fermentative, the initial production of denitrification proteome depends on energy from aerobic respiration. Thus, if a cell fails to synthesise a minimum of denitrification proteome before O2 is completely exhausted, it will be unable to produce it later due to energy-limitation. Such entrapment in anoxia is recently claimed to be a major phenomenon in batch cultures of the model organism Paracoccus denitrificans on the basis of measured e(--flow rates to O2 and NOx. Here we constructed a dynamic model and explicitly simulated actual kinetics of recruitment of the cells to denitrification to directly and more accurately estimate the recruited fraction (Fden. Transcription of nirS is pivotal for denitrification, for it triggers a cascade of events leading to the synthesis of a full-fledged denitrification proteome. The model is based on the hypothesis that nirS has a low probability (rden, h(-1 of initial transcription, but once initiated, the transcription is greatly enhanced through positive feedback by NO, resulting in the recruitment of the transcribing cell to denitrification. We assume that the recruitment is initiated as [O2] falls below a critical threshold and terminates (assuming energy-limitation as [O2] exhausts. With rden = 0.005 h(-1, the model robustly simulates observed denitrification kinetics for a range of culture conditions. The resulting Fden (fraction of the cells recruited to denitrification falls within 0.038-0.161. In contrast, if the recruitment of the entire population is assumed, the simulated denitrification kinetics deviate grossly from those observed. The phenomenon can be understood as a 'bet-hedging strategy': switching to denitrification is a gain if anoxic spell lasts long but is a waste

  14. Isolation of novel single-chain Cro proteins targeted for binding to the bcl-2 transcription initiation site by repertoire selection and subunit combinatorics.

    Science.gov (United States)

    Jonas, Kristina; Van Der Vries, Erhard; Nilsson, Mikael T I; Widersten, Mikael

    2005-11-01

    New designed DNA-binding proteins may be recruited to act as transcriptional regulators and could provide new therapeutic agents in the treatment of genetic disorders such as cancer. We have isolated tailored DNA-binding proteins selected for affinity to a region spanning the transcription initiation site of the human bcl-2 gene. The proteins were derived from a single-chain derivative of the lambda Cro protein (scCro), randomly mutated in its recognition helices to construct libraries of protein variants of distinct DNA-binding properties. By phage display-afforded affinity selections combined with recombination of shuffled subunits, protein variants were isolated, which displayed high affinity for the target bcl-2 sequence, as determined by electrophoretic mobility shift and biosensor assays. The proteins analyzed were moderately sequence-specific but provide a starting point for further maturation of desired function.

  15. Modeling the basal dynamics of p53 system.

    Directory of Open Access Journals (Sweden)

    Tingzhe Sun

    Full Text Available BACKGROUND: The tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Most previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses remain unchanged. Furthermore, the spontaneous pulses are filtered by ataxia telangiectasia mutated protein mediated posttranslational modifications and do not result in substantial p21 transcription. If challenged by externally severe DNA damage, cells generate synchronous p53 pulses and induce significantly high levels of p21. The high expression of p21 can also be partially induced by lowering the deacetylation rate. CONCLUSIONS: Our results demonstrated that the dynamics of p53 under nonstressed conditions is initiated by an excitable mechanism and cells become fully responsive only when cells are confronted with severe damage. These findings advance our understanding of the mechanism of p53 pulses and unlock many opportunities to p53-based therapy.

  16. Transcriptional Response in Mouse Thyroid Tissue after 211At Administration: Effects of Absorbed Dose, Initial Dose-Rate and Time after Administration.

    Directory of Open Access Journals (Sweden)

    Nils Rudqvist

    Full Text Available 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. However, a limitation has been the preferential accumulation of released 211At in the thyroid gland, which is a critical organ for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on genome-wide transcriptional expression in mouse thyroid gland.BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean thyroid absorbed doses of 0.023, 0.32, and 1.8 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively; mean thyroid absorbed dose was 1.4 Gy. Total RNA was extracted from pooled thyroids and the Illumina RNA microarray platform was used to determine mRNA levels. Differentially expressed transcripts and enriched GO terms were determined with adjusted p-value 1.5, and p-value <0.05, respectively.In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose at 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. Furthermore, similar regulation profiles were seen for groups administered 1.7 kBq. Interestingly, few previously proposed radiation responsive genes were detected in the present study. Regulation of immunological processes were prevalent at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy.

  17. The magic spot: a ppGpp binding site on E. coli RNA polymerase responsible for regulation of transcription initiation.

    Science.gov (United States)

    Ross, Wilma; Vrentas, Catherine E; Sanchez-Vazquez, Patricia; Gaal, Tamas; Gourse, Richard L

    2013-05-01

    The global regulatory nucleotide ppGpp ("magic spot") regulates transcription from a large subset of Escherichia coli promoters, illustrating how small molecules can control gene expression promoter-specifically by interacting with RNA polymerase (RNAP) without binding to DNA. However, ppGpp's target site on RNAP, and therefore its mechanism of action, has remained unclear. We report here a binding site for ppGpp on E. coli RNAP, identified by crosslinking, protease mapping, and analysis of mutant RNAPs that fail to respond to ppGpp. A strain with a mutant ppGpp binding site displays properties characteristic of cells defective for ppGpp synthesis. The binding site is at an interface of two RNAP subunits, ω and β', and its position suggests an allosteric mechanism of action involving restriction of motion between two mobile RNAP modules. Identification of the binding site allows prediction of bacterial species in which ppGpp exerts its effects by targeting RNAP.

  18. A downstream CpG island controls transcript initiation and elongation and the methylation state of the imprinted Airn macro ncRNA promoter.

    Directory of Open Access Journals (Sweden)

    Martha V Koerner

    Full Text Available A CpG island (CGI lies at the 5' end of the Airn macro non-protein-coding (nc RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start.

  19. Resistance to Streptomyces turgidiscabies in potato involves an early and sustained transcriptional reprogramming at initial stages of tuber formation.

    Science.gov (United States)

    Dees, Merete Wiken; Lysøe, Erik; Alsheikh, Muath; Davik, Jahn; Brurberg, May Bente

    2016-06-01

    Common scab, caused by species from the bacterial genus Streptomyces, is an important disease of potato (Solanum tuberosum) crops worldwide. Early tuberization is a critical period for pathogen infection; hence, studies of host gene expression responses during this developmental stage can be important to expand our understanding of the infection process and to identify putative resistance genes. In an infection experiment with the highly susceptible potato cultivar Saturna and the relatively resistant cultivar Beate, transcription profiles were obtained by RNA sequencing at two developmental stages: the early hook stage and the early tuber formation stage. Our results indicate that 'Beate' mounts an early and sustained response to infection by S. turgidiscabies, whereas the defence response by 'Saturna' ceases before the early tuber formation stage. Most pronounced were the putative candidate defence-associated genes uniquely expressed in 'Beate'. We observed an increase in alternative splicing on pathogen infection at the early hook stage for both cultivars. A significant down-regulation of genes involved in the highly energy-demanding process of ribosome biogenesis was observed for the infected 'Beate' plants at the early hook stage, which may indicate an allocation of resources that favours the expression of defence-related genes. PMID:26416294

  20. Rationale, Design, and Baseline Data of the Insulin Glargine (Lantus) Versus Insulin Detemir (Levemir) Treat-To-Target (L2T3) Study: A Multinational, Randomized Noninferiority Trial of Basal Insulin Initiation in Type 2 Diabetes

    NARCIS (Netherlands)

    S.G.H.A. Swinnen; F.J. Snoek; M.P. Dain; J.H. DeVries; J.B.L. Hoekstra; F. Holleman

    2009-01-01

    Objective: To discuss the design and baseline data of the Lantus (R) (sanofi-aventis, Paris, France) versus Levemir (R) (Novo Nordisk A/S, Bagsvaerd, Denmark) Treat-To-Target (L2T3) study, a multinational, randomized comparison between the basal insulin analogs insulin glargine and insulin detemir.

  1. Basal and apical regulation of VEGF-A and placenta growth factor in the RPE/choroid and primary RPE

    Science.gov (United States)

    Kaya, Leyla; Flach, Janina; Lassen, Jens; Treumer, Felix; Roider, Johann

    2015-01-01

    Purpose Members of the vascular endothelial growth factor (VEGF) family are strongly involved in pathological processes in the retina, such as age-related macular degeneration and diabetic retinopathy. Cells of the retinal pigment epithelium (RPE) constitutively secrete VEGF-A, and the secretion of placental growth factor (PlGF) has also been described. RPE cells are strongly polarized cells with different secretome at the apical and basal side. In this study, we evaluated the basal and apical regulation of VEGF-A and PlGF secretion in RPE/choroid explants and primary RPE cells. Methods RPE/choroid tissue explants were prepared from porcine eyes and cultivated in modified Ussing chambers, separating apical (RPE) and basal (choroid) supernatant. Primary RPE cells were also prepared from porcine eyes and cultivated on Transwell plates. Explants and cells were treated with inhibitors for VEGFR-2 (SU1498), p38 (SB203580), and the transcription factors nuclear factor-kappa B (NF-κB) and SP-1 (mithramycin), respectively. VEGF-A and PlGF content was evaluated with enzyme-linked immunosorbent assay (ELISA). In addition, western blots were performed. Results In the RPE/choroid, VEGF-A can initially be found on the apical and basal sides with significantly more pronounced secretion on the basal side. VEGF-A secretion is differentially regulated on the apical and basal sides, with the inhibition of SP-1 and NF-κB showing strong effects apically and basally after 24 h and 48 h, the inhibition of p38 displaying its effect mainly on the basal side with some effect apically after 48 h, and the inhibition of VEGFR-2 reducing the secretion of VEGF only on the apical side at 24 h and 48 h. In the RPE cell culture, similar effects were found, with inhibition of NF-κB or SP-1 displaying a strong decrease in VEGF-A on both sides, and p38 inhibition displaying only an inhibitory effect on the basal side. In contrast, an apical effect of VEGFR-2 inhibition was not found. However, the

  2. Distinctive Patterns of CTNNB1 (β-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma.

    Science.gov (United States)

    Jo, Vickie Y; Sholl, Lynette M; Krane, Jeffrey F

    2016-08-01

    Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harbor CTNNB1 mutations, and nuclear β-catenin expression is prevalent. We evaluated β-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. β-catenin immunohistochemistry was performed on formalin-fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear β-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial-myoepithelial carcinomas showed focal nuclear staining. Most β-catenin-negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3 CTNNB1 mutations, all c.104T>C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations in PIK3CA, biallelic inactivation of NFKBIA, focal CYLD deletion, and without CTNNB1 mutation despite focal β-catenin expression. Nuclear β-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics. CTNNB1 mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-κB pathways and transcriptional regulation. PMID:27259009

  3. Recruitment of the transcriptional coactivator HCF-1 to viral immediate-early promoters during initiation of reactivation from latency of herpes simplex virus type 1.

    Science.gov (United States)

    Whitlow, Zackary; Kristie, Thomas M

    2009-09-01

    The transcriptional coactivator host cell factor 1 (HCF-1) is critical for the expression of immediate-early (IE) genes of the alphaherpesviruses herpes simplex virus type 1 (HSV-1) and varicella-zoster virus. HCF-1 may also be involved in the reactivation of these viruses from latency as it is sequestered in the cytoplasm of sensory neurons but is rapidly relocalized to the nucleus upon stimulation that results in reactivation. Here, chromatin immunoprecipitation assays demonstrate that HCF-1 is recruited to IE promoters of viral genomes during the initiation of reactivation, correlating with RNA polymerase II occupancy and IE expression. The data support the model whereby HCF-1 plays a pivotal role in the reactivation of HSV-1 from latency.

  4. Analyses of in vivo interactions between transcription factors and the archaeal RNA polymerase.

    Science.gov (United States)

    Walker, Julie E; Santangelo, Thomas J

    2015-09-15

    Transcription factors regulate the activities of RNA polymerase (RNAP) at each stage of the transcription cycle. Many basal transcription factors with common ancestry are employed in eukaryotic and archaeal systems that directly bind to RNAP and influence intramolecular movements of RNAP and modulate DNA or RNA interactions. We describe and employ a flexible methodology to directly probe and quantify the binding of transcription factors to RNAP in vivo. We demonstrate that binding of the conserved and essential archaeal transcription factor TFE to the archaeal RNAP is directed, in part, by interactions with the RpoE subunit of RNAP. As the surfaces involved are conserved in many eukaryotic and archaeal systems, the identified TFE-RNAP interactions are likely conserved in archaeal-eukaryal systems and represent an important point of contact that can influence the efficiency of transcription initiation.

  5. Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

    Science.gov (United States)

    Sorolla, A.; Ho, D.; Wang, E.; Evans, C. W.; Ormonde, C. F. G.; Rashwan, R.; Singh, R.; Iyer, K. Swaminathan; Blancafort, P.

    2016-04-01

    Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary

  6. Long-noncoding RNAs in basal cell carcinoma.

    Science.gov (United States)

    Sand, Michael; Bechara, Falk G; Sand, Daniel; Gambichler, Thilo; Hahn, Stephan A; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

    2016-08-01

    Long noncoding RNAs (lncRNAs) are fundamental regulators of pre- and post-transcriptional gene regulation. Over 35,000 different lncRNAs have been described with some of them being involved in cancer formation. The present study was initiated to describe differentially expressed lncRNAs in basal cell carcinoma (BCC). Patients with BCC (n = 6) were included in this study. Punch biopsies were harvested from the tumor center and nonlesional epidermal skin (NLES, control, n = 6). Microarray-based lncRNA and mRNA expression profiles were identified through screening for 30,586 lncRNAs and 26,109 protein-coding transcripts (mRNAs). The microarray data were validated by RT-PCR in a second set of BCC versus control samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of mRNAs were performed to assess biologically relevant pathways. A total of 1851 lncRNAs were identified as being significantly up-regulated, whereas 2165 lncRNAs were identified as being significantly down-regulated compared to nonlesional skin (p < 0.05). Oncogenic and/or epidermis-specific lncRNAs, such as CASC15 or ANRIL, were among the differentially expressed sequences. GO analysis showed that the highest enriched GO targeted by up-regulated transcripts was "extracellular matrix." KEGG pathway analysis showed the highest enrichment scores in "Focal adhesion." BCC showed a significantly altered lncRNA and mRNA expression profile. Dysregulation of previously described lncRNAs may play a role in the molecular pathogenesis of BCC and should be subject of further analysis. PMID:26861560

  7. Site-specific basal body duplication in Chlamydomonas.

    Science.gov (United States)

    O'Toole, Eileen T; Dutcher, Susan K

    2014-02-01

    Correct centriole/basal body positioning is required for numerous biological processes, yet how the cell establishes this positioning is poorly understood. Analysis of centriolar/basal body duplication provides a key to understanding basal body positioning and function. Chlamydomonas basal bodies contain structural features that enable specific triplet microtubules to be specified. Electron tomography of cultures enriched in mitotic cells allowed us to follow basal body duplication and identify a specific triplet at which duplication occurs. Probasal bodies elongate in prophase, assemble transitional fibers (TF) and are segregated with a mature basal body near the poles of the mitotic spindle. A ring of nine-singlet microtubules is initiated at metaphase, orthogonal to triplet eight. At telophase/cytokinesis, triplet microtubule blades assemble first at the distal end, rather than at the proximal cartwheel. The cartwheel undergoes significant changes in length during duplication, which provides further support for its scaffolding role. The uni1-1 mutant contains short basal bodies with reduced or absent TF and defective transition zones, suggesting that the UNI1 gene product is important for coordinated probasal body elongation and maturation. We suggest that this site-specific basal body duplication ensures the correct positioning of the basal body to generate landmarks for intracellular patterning in the next generation. PMID:24166861

  8. Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Kornecki Elizabeth

    2011-06-01

    Full Text Available Abstract Background - The F11 Receptor (F11R; aka JAM-A, JAM-1 is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs. Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the de-novo transcription and translation of F11R molecules, induced in ECs by exposure to inflammatory cytokines. Methods - The experimental approach utilized isolated, washed human platelet suspensions and cultured human venous endothelial cells (HUVEC and human arterial endothelial cells (HAEC exposed to the proinflammatory cytokines TNF-alpha and/or IFN-gamma, for examination of the ability of human platelets to adhere to the inflamed ECs thru the F11R. Our strategy was based on testing the effects of the following inhibitors on this activity: general mRNA synthesis inhibitors, inhibitors of the NF-kappaB and JAK/STAT pathways, and small interfering F11R-mRNA (siRNAs to specifically silence the F11R gene. Results - Treatment of inflamed ECs with the inhibitors actinomycin, parthenolide or with AG-480 resulted in complete blockade of F11R- mRNA expression, indicating the involvement of NF-kappaB and JAK/STAT pathways in this induction. Transfection of ECs with F11R siRNAs caused complete inhibition of the cytokine-induced upregulation of F11R mRNA and inhibition of detection of the newly- translated F11R molecules in cytokine-inflamed ECs. The functional consequence of the inhibition of F11R transcription and translation was the significant blockade of the adhesion of human platelets to inflamed ECs. Conclusion - These results prove that de novo synthesis

  9. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  10. A novel embryological theory of autism causation involving endogenous biochemicals capable of initiating cellular gene transcription: a possible link between twelve autism risk factors and the autism 'epidemic'.

    Science.gov (United States)

    King, Chiara R

    2011-05-01

    Human alpha-fetoprotein is a pregnancy-associated protein with an undetermined physiological role. As human alpha-fetoprotein binds retinoids and inhibits estrogen-dependent cancer cell proliferation, and because retinoic acid (a retinol metabolite) and estradiol (an estrogen) can both initiate cellular gene transcription, it is hypothesized here that alpha-fetoprotein functions during critical gestational periods to prevent retinoic acid and maternal estradiol from inappropriately stimulating gene expression in developing brain regions which are sensitive to these chemicals. Prenatal/maternal factors linked to increased autism risk include valproic acid, thalidomide, alcohol, rubella, cytomegalovirus, depression, schizophrenia, obsessive-compulsive disorder, autoimmune disease, stress, allergic reaction, and hypothyroidism. It will be shown how each of these risk factors may initiate expression of genes which are sensitive to retinoic acid and/or estradiol - whether by direct promotion or by reducing production of alpha-fetoprotein. It is thus hypothesized here that autism is not a genetic disorder, but is rather an epigenetic disruption in brain development caused by gestational exposure to chemicals and/or conditions which either inhibit alpha-fetoprotein production or directly promote retinoic acid-sensitive or estradiol-sensitive gene expression. This causation model leads to potential chemical explanations for autistic brain morphology, the distinct symptomatology of Asperger's syndrome, and the differences between high-functioning and low-functioning autism with regard to mental retardation, physical malformation, and sex ratio. It will be discussed how folic acid may cause autism under the retinoic acid/estradiol model, and the history of prenatal folic acid supplementation will be shown to coincide with the history of what is popularly known as the autism epidemic. It is thus hypothesized here that prenatal folic acid supplementation has contributed to the

  11. Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo.

    Science.gov (United States)

    Saha, Achinto; Blando, Jorge; Fernandez, Irina; Kiguchi, Kaoru; DiGiovanni, John

    2016-05-01

    A cell line was established from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, are LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. Furthermore, HMVP2 cells form spheroids and both the cells and spheroids produce tumors in syngeneic mice. After four days of culture, HMVP2 spheroids underwent a gradual transition from LinnegSca-1highCD49fhigh expression to LinnegSca-1lowCD49flow while a subpopulation of the cells retained the original LinnegSca-1highCD49fhigh expression pattern. Additional cell subpopulations expressing Lin positive markers were also present suggesting further differentiation of HMVP2 spheroids. Two additional highly tumorigenic cell lines (HMVP2A1 and HMVP2A2) were isolated from HMVP2 cells after subsequent tumor formation in FVB/N mice. Concurrently, we also established cell lines from the VP of 6 months old Hi-Myc mice (named as HMVP1) and FVB/N mice (called NMVP) having less aggressive growth properties compared to the other three cell lines. AR expression was reduced in HMVP2 cells compared to NMVP and HMVP1 cells and almost absent in HMVP2A1 and HMVP2A2 cells. These cell lines will provide valuable tools for further mechanistic studies as well as preclinical studies to evaluate preventive and/or therapeutic agents for prostate cancer.

  12. The candidate histocompatibility locus of a Basal chordate encodes two highly polymorphic proteins.

    Directory of Open Access Journals (Sweden)

    Marie L Nydam

    Full Text Available The basal chordate Botryllus schlosseri undergoes a natural transplantation reaction governed by a single, highly polymorphic locus called the fuhc. Our initial characterization of this locus suggested it encoded a single gene alternatively spliced into two transcripts: a 555 amino acid-secreted form containing the first half of the gene, and a full-length, 1008 amino acid transmembrane form, with polymorphisms throughout the ectodomain determining outcome. We have now found that the locus encodes two highly polymorphic genes which are separated by a 227 bp intergenic region: first, the secreted form as previously described, and a second gene encoding a 531 amino acid membrane-bound gene containing three extracellular immunoglobulin domains. While northern blotting revealed only these two mRNAs, both PCR and mRNA-seq detect a single capped and polyadenylated transcript that encodes processed forms of both genes linked by the intergenic region, as well as other transcripts in which exons of the two genes are spliced together. These results might suggest that the two genes are expressed as an operon, during which both genes are co-transcribed and then trans-spliced into two separate messages. This type of transcriptional regulation has been described in tunicates previously; however, the membrane-bound gene does not encode a typical Splice Leader (SL sequence at the 5' terminus that usually accompanies trans-splicing. Thus, the presence of stable transcripts encoding both genes may suggest a novel mechanism of regulation, or conversely may be rare but stable transcripts in which the two mRNAs are linked due to a small amount of read-through by RNA polymerase. Both genes are highly polymorphic and co-expressed on tissues involved in histocompatibility. In addition, polymorphisms on both genes correlate with outcome, although we have found a case in which it appears that the secreted form may be major allorecognition determinant.

  13. Cardiovascular effects of basal insulins.

    Science.gov (United States)

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  14. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    DEFF Research Database (Denmark)

    Su, Ying; Subedee, Ashim; Bloushtain-Qimron, Noga;

    2015-01-01

    genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree......Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated...... of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required...

  15. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  16. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Geetaram; Farley, Kalamo [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); El-Hage, Nazira [Virginia Commonwealth University, Richmond, VA (United States); Aiamkitsumrit, Benjamas; Fassnacht, Ryan [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Kashanchi, Fatah [George Mason University, Manassas, VA (United States); Ochem, Alex [ICGEB, Wernher and Beit Building, Anzio Road, Observatory, 7925 Cape Town (South Africa); Simon, Gary L. [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Karn, Jonathan [Case Western Reserve University, Cleveland, OH (United States); Hauser, Kurt F. [Virginia Commonwealth University, Richmond, VA (United States); Tyagi, Mudit, E-mail: tmudit@email.gwu.edu [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037 (United States)

    2015-09-15

    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR.

  17. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

    International Nuclear Information System (INIS)

    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR

  18. Experimental characterization of Cis-acting elements important for translation and transcription in halophilic archaea.

    Directory of Open Access Journals (Sweden)

    Mariam Brenneis

    2007-12-01

    Full Text Available The basal transcription apparatus of archaea is well characterized. However, much less is known about the mechanisms of transcription termination and translation initation. Recently, experimental determination of the 5'-ends of ten transcripts from Pyrobaculum aerophilum revealed that these are devoid of a 5'-UTR. Bioinformatic analysis indicated that many transcripts of other archaeal species might also be leaderless. The 5'-ends and 3'-ends of 40 transcripts of two haloarchaeal species, Halobacterium salinarum and Haloferax volcanii, have been determined. They were used to characterize the lengths of 5'-UTRs and 3'-UTRs and to deduce consensus sequence-elements for transcription and translation. The experimental approach was complemented with a bioinformatics analysis of the H. salinarum genome sequence. Furthermore, the influence of selected 5'-UTRs and 3'-UTRs on transcript stability and translational efficiency in vivo was characterized using a newly established reporter gene system, gene fusions, and real-time PCR. Consensus sequences for basal promoter elements could be refined and a novel element was discovered. A consensus motif probably important for transcriptional termination was established. All 40 haloarchaeal transcripts analyzed had a 3'-UTR (average size 57 nt, and their 3'-ends were not posttranscriptionally modified. Experimental data and genome analyses revealed that the majority of haloarchaeal transcripts are leaderless, indicating that this is the predominant mode for translation initiation in haloarchaea. Surprisingly, the 5'-UTRs of most leadered transcripts did not contain a Shine-Dalgarno (SD sequence. A genome analysis indicated that less than 10% of all genes are preceded by a SD sequence and even most proximal genes in operons lack a SD sequence. Seven different leadered transcripts devoid of a SD sequence were efficiently translated in vivo, including artificial 5'-UTRs of random sequences. Thus, an interaction of

  19. Role of cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) in the initiation of mitochondrial biogenesis and stress response in liver cells.

    Science.gov (United States)

    Than, Tin Aung; Lou, Huan; Ji, Cheng; Win, Sanda; Kaplowitz, Neil

    2011-06-24

    Peroxisome proliferator-activated receptor α, coactivator 1α (PGC-1α) is the master regulator of mitochondrial biogenesis. PGC-1α expression is under the control of the transcription factor, cAMP-responsive element-binding protein (CREB). In searching for candidate transcription factors that mediate mitochondrial stress-initiated mitochondria-to-nucleus signaling in the regulation of mitochondrial biogenesis, we assessed the effect of silencing CREB-regulated transcription co-activators (CRTC). CRTC isoforms are co-activators of CREB-regulated transcription by a CREB phosphorylation-independent pathway. Using cultured HepG2 cells and primary mouse hepatocytes, we determined that mitochondrial stress imposed by the complex I inhibitor rotenone elicited mitochondrial biogenesis, which was dependent on an induction of PGC-1α, which was inhibited by silencing PGC-1α. PGC-1α induction in response to rotenone was inhibited by silencing the expression of CRTC3, which blocked downstream mitochondria biogenesis. In contrast, silencing CRTC2 did not affect the induction of this pathway in response to rotenone. Thus, CRTC3 plays a selective role in mitochondrial biogenesis in response to rotenone.

  20. Identification and initial characterization of the 3' end of gene transcripts encoding putative members of the pheromone receptor subfamily in Lepidoptera

    Institute of Scientific and Technical Information of China (English)

    Stephen F. Garczynski; Kevin W. Wanner; Thomas R. Unruh

    2012-01-01

    Semiochemicals,including pheromones and kairomones,used in pest management programs reduce the need for chemical insecticides,and understanding their interactions with their membrane receptors may help make them more effective in the field.Identification of odorant receptors in the Lepidoptera has mainly been achieved using bioinformatics to search DNA sequences generated by genome or expressed sequence tag (EST) sequencing projects.This study reports a rapid method to identify members of the pheromone receptor subfamily in Lepidoptera.Degenerate oligonucleotide primers were designed against a conserved amino acid sequence in the carboxyl terminus of known lepidopteran pheromone receptors,and the primers were used in a 3' rapid amplification of complementary DNA (cDNA) ends procedure.Polymerase chain reaction products generated from seven different lepidopteran species were TA cloned and sequenced.The eDNA sequences of 25 transcripts were determined to encode potential members of the pheromone receptor subfamily.These cDNAs ranged from 238 to 642 bp and encoded 49-54 amino acids of the carboxyl terminus.Analysis of the 3' untranslated region reveals that most of the transcripts contain multiple polyadenylation signal sequences,and in the case ofManduca sexta,an alternate polyadenylation signal appears to be used in transcript processing.The 3' untranslated region was also useful in determining unique receptors encoded by transcripts having highly similar nucleotide and amino acid sequences.Overall,this technique provides a complementary method of pheromone receptor identification in EST sequencing projects,or can be used as a stand-alone method in conjunction with 5' rapid amplification of cDNA ends procedures.

  1. Karsinoma Sel Basal Pada Wajah

    OpenAIRE

    Hastuti

    2008-01-01

    Karsinoma sel basal merupakan tumor ganas pada lapisan epidermis kulit yang paling umum dijumpai. Lokasi tumor iui paling banyak pada wajah dibandingkan anggota tubuh lainnya. Etiologi tumor iui diduga berhubungan dengan cahaya matahari yang mengandung sinar ultraviolet yang karsinogenik. Klasifikasi tumor ini dibagi berdasarkan gambaran kliuis dan histopatologisnya. Diagnosa tumor ini dapat ditegakkan dengan pemeriksaan k1inis dan histologis, pemeriksaan radiologis jarang digunakan. Diag...

  2. Basal body structure in Trichonympha.

    Science.gov (United States)

    Guichard, Paul; Gönczy, Pierre

    2016-01-01

    Trichonympha is a symbiotic flagellate of many species of termites and of the wood-feeding cockroach. Remarkably, this unicellular organism harbors up to over ten thousand flagella on its surface, which serve to propel it through the viscous environment of the host hindgut. In the 1960s, analysis of resin-embedded Trichonympha samples by electron microscopy revealed that the basal bodies that give rise to these flagella are exceptionally long, with a proximal, cartwheel-bearing, region some 50 times longer than that of regular centrioles. In recent years, this salient feature has prompted the analysis of the 3D architecture of Trichonympha basal bodies in the native state using cryo-electron tomography. The resulting ~40 Å resolution map of the basal body proximal region revealed a number of novel features that may be conserved in centrioles of other systems. These include proximal-distal polarity of the pinhead structure that links the cartwheel to centriolar microtubules, as well as of the linker between the A and the C microtubules. Moreover, this work demonstrated that the cartwheel is made of stacked ring-like structures that likely each comprise 18 molecules of SAS-6 proteins. PMID:26937279

  3. Transcriptional regulation by nonclassical action of thyroid hormone

    Directory of Open Access Journals (Sweden)

    Moeller Lars C

    2011-08-01

    Full Text Available Abstract Thyroid hormone (TH is essential for normal development, growth and metabolism. Its effects were thought to be principally mediated through triiodothyronine (T3, acting as a ligand for the nuclear TH receptors (TRs α and β residing on thyroid hormone response elements (TREs in the promoter of TH target genes. In this classical model of TH action, T3 binding to TRs leads to recruitment of basal transcription factors and increased transcription of TH responsive genes. Recently, the concept of TH action on gene expression has become more diverse and now includes nonclassical actions of T3 and T4: T3 has been shown to activate PI3K via the TRs, which ultimately increases transcription of certain genes, e.g. HIF-1α. Additionally, both T3 and thyroxine (T4 can bind to a membrane integrin, αvβ3, which leads to activation of the PI3K and MAPK signal transduction pathways and finally also increases gene transcription, e.g. of the FGF2 gene. Therefore, these initially nongenomic, nonclassical actions seem to serve as additional interfaces for transcriptional regulation by TH. Aim of this perspective is to summarize the genes that are currently known to be induced by nonclassical TH action and the mechanisms involved.

  4. Basal cell carcinoma of penis: case report.

    OpenAIRE

    Sulaiman, M Z; Polacarz, S V; Partington, P E

    1988-01-01

    Basal cell carcinoma of the penis is rare. A patient who presented with a penile and scrotal ulcer due to basal cell carcinoma is reported. Wide local excision and split skin grafting were performed to excise the lesion completely.

  5. The basal bodies of Chlamydomonas reinhardtii

    OpenAIRE

    Dutcher, Susan K.; O’Toole, Eileen T.

    2016-01-01

    The unicellular green alga, Chlamydomonas reinhardtii, is a biflagellated cell that can swim or glide. C. reinhardtii cells are amenable to genetic, biochemical, proteomic, and microscopic analysis of its basal bodies. The basal bodies contain triplet microtubules and a well-ordered transition zone. Both the mother and daughter basal bodies assemble flagella. Many of the proteins found in other basal body-containing organisms are present in the Chlamydomonas genome, and mutants in these genes...

  6. Transcription Dynamics in Living Cells.

    Science.gov (United States)

    Lenstra, Tineke L; Rodriguez, Joseph; Chen, Huimin; Larson, Daniel R

    2016-07-01

    The transcription cycle can be roughly divided into three stages: initiation, elongation, and termination. Understanding the molecular events that regulate all these stages requires a dynamic view of the underlying processes. The development of techniques to visualize and quantify transcription in single living cells has been essential in revealing the transcription kinetics. They have revealed that (a) transcription is heterogeneous between cells and (b) transcription can be discontinuous within a cell. In this review, we discuss the progress in our quantitative understanding of transcription dynamics in living cells, focusing on all parts of the transcription cycle. We present the techniques allowing for single-cell transcription measurements, review evidence from different organisms, and discuss how these experiments have broadened our mechanistic understanding of transcription regulation.

  7. Conserved TAAATG sequence at the transcriptional and translational initiation sites of vaccinia virus late genes deduced by structural and functional analysis of the HindIII H genome fragment.

    Science.gov (United States)

    Rosel, J L; Earl, P L; Weir, J P; Moss, B

    1986-11-01

    The sequence of the 8,600-base-pair HindIII H fragment, located at the center of the vaccinia virus genome, was determined to analyze several late genes. Seven major complete open reading frames (ORFs) and two that started from or continued into adjacent DNA segments were identified. ORFs were closely spaced and present on both DNA strands. Some adjacent ORFs had oppositely oriented overlapping termination codons or contiguous stop and start codons. Nucleotide compositional analysis indicated that the A-T frequency was consistently lowest in the first codon position. The sizes of the polypeptides predicted from the DNA sequence were compared with those determined by polyacrylamide gel electrophoresis of cell-free translation products of mRNAs selected by hybridization to cloned single-stranded DNA segments or synthesized in vitro by bacteriophage T7 RNA polymerase. Six transcripts that initiated within the HindIII H DNA fragment were detected, and of these, four were synthesized only at late times, one was synthesized only early, and one was synthesized early and late. The sites on the genome corresponding to the 5' ends of the transcripts were located by high-resolution nuclease S1 analysis. For late genes, the transcriptional and translational initiation sites mapped within a few nucleotides of each other, and in each case the sequence TAAATGG occurred at the start of the ORF. The extremely short leader and the absence of A or G in the -3 position, relative to the first nucleotide of the initiation codon, distinguishes the majority of vaccinia virus late genes from eucaryotic and vaccinia virus early genes.

  8. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  9. Basal cell carcinoma-treatment with cryosurgery

    OpenAIRE

    Kaur S; Thami G; Kanwar A

    2003-01-01

    Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  10. The basal bodies of Chlamydomonas reinhardtii.

    Science.gov (United States)

    Dutcher, Susan K; O'Toole, Eileen T

    2016-01-01

    The unicellular green alga, Chlamydomonas reinhardtii, is a biflagellated cell that can swim or glide. C. reinhardtii cells are amenable to genetic, biochemical, proteomic, and microscopic analysis of its basal bodies. The basal bodies contain triplet microtubules and a well-ordered transition zone. Both the mother and daughter basal bodies assemble flagella. Many of the proteins found in other basal body-containing organisms are present in the Chlamydomonas genome, and mutants in these genes affect the assembly of basal bodies. Electron microscopic analysis shows that basal body duplication is site-specific and this may be important for the proper duplication and spatial organization of these organelles. Chlamydomonas is an excellent model for the study of basal bodies as well as the transition zone. PMID:27252853

  11. Prolactin-induced prostate tumorigenesis links sustained Stat5 signaling with the amplification of basal/stem cells and emergence of putative luminal progenitors.

    Science.gov (United States)

    Sackmann-Sala, Lucila; Chiche, Aurélie; Mosquera-Garrote, Nerea; Boutillon, Florence; Cordier, Corinne; Pourmir, Ivan; Pascual-Mathey, Luz; Kessal, Karima; Pigat, Natascha; Camparo, Philippe; Goffin, Vincent

    2014-11-01

    Current androgen ablation therapies for prostate cancer are initially successful, but the frequent development of castration resistance urges the generation of alternative therapies and represents an important health concern. Prolactin/signal transducer and activator of transcription 5 (STAT5) signaling is emerging as a putative target for alternative treatment for prostate cancer. However, mechanistic data for its role in development or progression of prostate tumors are scarce. In vivo mouse studies found that local prolactin induced the amplification of prostate epithelial basal/stem cells. Because these cells are proposed cells of origin for prostate cancer and disease recurrence, we looked further into this amplification. Our results indicated that sustained Stat5 activation was associated with the occurrence of abnormal basal/stem cell clusters in prostate epithelium of prostate-specific prolactin-transgenic mice. Analysis of epithelial areas containing these clusters found high proliferation, Stat5 activation, and expression of stem cell antigen 1. Furthermore, enhanced prolactin signaling also led to amplification of a luminal cell population that was positive for stem cell antigen 1. These cells may originate from amplified basal/stem cells and might represent important progenitors for tumor development in prostate epithelium. These data provide a deeper understanding of the initial stages of prostate tumorigenesis induced by prolactin to help determine whether this hormone or its downstream messengers could be useful targets for prostate cancer treatment in the future.

  12. Endoscopic considerations treating hydrocephalus caused by basal ganglia and large thalamic tumors

    Directory of Open Access Journals (Sweden)

    Jonathan Roth

    2015-01-01

    Conclusions: Endoscopic surgery may potentially play a significant role in the initial management of patients with large basal ganglia and large thalamic tumors causing obstructive hydrocephalus. Technical nuances and individualized goals are crucial for optimal outcomes.

  13. The cell cycle rallies the transcription cycle: Cdc28/Cdk1 is a cell cycle-regulated transcriptional CDK.

    Science.gov (United States)

    Chymkowitch, Pierre; Enserink, Jorrit M

    2013-01-01

    In the budding yeast Saccharomyces cerevisiae, the cyclin-dependent kinases (CDKs) Kin28, Bur1 and Ctk1 regulate basal transcription by phosphorylating the carboxyl-terminal domain (CTD) of RNA polymerase II. However, very little is known about the involvement of the cell cycle CDK Cdc28 in the transcription process. We have recently shown that, upon cell cycle entry, Cdc28 kinase activity boosts transcription of a subset of genes by directly stimulating the basal transcription machinery. Here, we discuss the biological significance of this finding and give our view of the kinase-dependent role of Cdc28 in regulation of RNA polymerase II.

  14. An upstream activation element exerting differential transcriptional activation on an archaeal promoter

    DEFF Research Database (Denmark)

    Peng, Nan; Xia, Qiu; Chen, Zhengjun;

    2009-01-01

    (UAS) ara-box activated the basal promoter by recruiting transcription factor B to its BRE. While this UAS ensured a general expression from an inactive or weak basal promoter in the presence of other tested carbon resources, it exhibited a strong arabinose-responsive transcriptional activation. To our...

  15. HAT activity is essential for CBP-1-dependent transcription and differentiation in Caenorhabditis elegans

    OpenAIRE

    Victor, Martin; Bei, Yanxia; Gay, Frédérique; Calvo, Dominica; Mello, Craig; Shi, Yang

    2002-01-01

    The p300/CBP family of transcriptional coactivators possesses multiple functional domains, including a histone acetyltransferase (HAT) and several activation domains. A number of models have been proposed to account for their roles in transcriptional activation, including interactions with basal transcription machinery and chromatin remodeling. However, individual contributions of these domains to transcriptional activation and their significance in living organisms remain unclear. We address...

  16. Covert skill learning in a cortical-basal ganglia circuit.

    Science.gov (United States)

    Charlesworth, Jonathan D; Warren, Timothy L; Brainard, Michael S

    2012-06-14

    We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning; influential 'actor-critic' models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire. Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit, contributes to skill learning even when it does not contribute to such 'exploratory' variation in behavioural performance during training. Blocking the output of the AFP while training Bengalese finches to modify their songs prevented the gradual improvement that normally occurs in this complex skill during training. However, unblocking the output of the AFP after training caused an immediate transition from naive performance to excellent performance, indicating that the AFP covertly gained the ability to implement learned skill performance without contributing to skill practice. In contrast, inactivating the output nucleus of the AFP during training completely prevented learning, indicating that learning requires activity within the AFP during training. Our results suggest a revised model of skill learning: basal ganglia circuits can monitor the consequences of behavioural variation produced by other brain regions and then direct those brain regions to implement more successful behaviours. The ability of the AFP to identify successful performances generated by other brain regions indicates that basal ganglia circuits receive a detailed efference copy of premotor activity in those regions. The capacity of the AFP to implement successful performances that were initially produced by other brain regions indicates precise functional connections between basal ganglia circuits and the motor regions that directly control performance. PMID:22699618

  17. Positron emission tomography and basal ganglia functions

    International Nuclear Information System (INIS)

    With the advent of positron emission tomography (PET), studies on the human brain function and pathophysiology of brain damage have been extremely progressed. It is well-known that the basal ganglia plays an important role as one of the central nervous system involved in exercise regulation. More recently, the potential involvement of the basal ganglia in psychological processes, such as cognitive function, has been pointed out, receiving much attention. In spite of such a lot of studies, however, basal ganglia function remains unclear. This paper describes the relationships between PET findings and basal ganglia function. PET findings are discussed in relation to brain energy metabolism and striatal dopamine function. Pathophysiology of the basal ganglia are described in terms of the following diseases: Parkinson's disease, Parkinson's syndrome, progressive supranuclear palsy, Huntington's disease, and dystonia. Physiological backgrounds of the basal ganglia for PET images are also referred to. (N.K.) 75 refs

  18. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    Directory of Open Access Journals (Sweden)

    Divvya

    2014-05-01

    Full Text Available Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differentiation is practically very rare.

  19. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    OpenAIRE

    Divvya; Rehana; Viswanathan; Krishnaswamy; Anvar Ali

    2014-01-01

    Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differen...

  20. Functional Neuroanatomy of the Basal Ganglia

    OpenAIRE

    Lanciego, José L.; Luquin, Natasha; Obeso, José A.

    2012-01-01

    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amp...

  1. Striatal plasticity and basal ganglia circuit function

    OpenAIRE

    Kreitzer, Anatol C.; Malenka, Robert C.

    2008-01-01

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways—distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive m...

  2. Neglected Giant Scalp Basal Cell Carcinoma

    OpenAIRE

    Anne Kristine Larsen, MD; Waseem-Asim Ghulam El-Charnoubi, MD; Julie Gehl, MD, PhD; Christen Krag, MD, PhD

    2014-01-01

    Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstruct...

  3. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    OpenAIRE

    Yeliz Bilir; Erkan Gokce; Banu Ozturk; Faik Alev Deresoy; Ruken Yuksekkaya; Emel Yaman

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity...

  4. Striatal plasticity and basal ganglia circuit function.

    Science.gov (United States)

    Kreitzer, Anatol C; Malenka, Robert C

    2008-11-26

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways, which are distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function. PMID:19038213

  5. Ubiquitin and proteasomes in transcription.

    Science.gov (United States)

    Geng, Fuqiang; Wenzel, Sabine; Tansey, William P

    2012-01-01

    Regulation of gene transcription is vitally important for the maintenance of normal cellular homeostasis. Failure to correctly regulate gene expression, or to deal with problems that arise during the transcription process, can lead to cellular catastrophe and disease. One of the ways cells cope with the challenges of transcription is by making extensive use of the proteolytic and nonproteolytic activities of the ubiquitin-proteasome system (UPS). Here, we review recent evidence showing deep mechanistic connections between the transcription and ubiquitin-proteasome systems. Our goal is to leave the reader with a sense that just about every step in transcription-from transcription initiation through to export of mRNA from the nucleus-is influenced by the UPS and that all major arms of the system--from the first step in ubiquitin (Ub) conjugation through to the proteasome-are recruited into transcriptional processes to provide regulation, directionality, and deconstructive power. PMID:22404630

  6. Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin.

    Science.gov (United States)

    Zhang, Haiying; Pasolli, H Amalia; Fuchs, Elaine

    2011-02-01

    In mammals, skin begins as a single-layered epithelium, which, through a series of signals, either stratifies and differentiates to become epidermis or invaginates downward to make hair follicles (HFs). To achieve and maintain proper tissue architecture, keratinocytes must intricately balance growth and differentiation. Here, we uncover a critical and hitherto unappreciated role for Yes-associated protein (YAP), an evolutionarily conserved transcriptional coactivator with potent oncogenic potential. We show that YAP is highly expressed and nuclear in single-layered basal epidermal progenitors. Notably, nuclear YAP progressively declines with age and correlates with proliferative potential of epidermal progenitors. Shortly after initiation of HF morphogenesis, YAP translocates to the cytoplasm of differentiating cells. Through genetic analysis, we demonstrate a role for YAP in maintaining basal epidermal progenitors and regulating HF morphogenesis. YAP overexpression causes hair placodes to evaginate into epidermis rather than invaginate into dermis. YAP also expands basal epidermal progenitors, promotes proliferation, and inhibits terminal differentiation. In vitro gain-and-loss of function studies show that primary mouse keratinocytes (MKs) accelerate proliferation, suppress differentiation, and inhibit apoptosis when YAP is activated and reverse these features when YAP is inhibited. Finally, we identify Cyr61 as a target of YAP in MKs and demonstrate a requirement for TEA domain (TEAD) transcriptional factors to comediate YAP functions in MKs.

  7. Readiness in the Basal Reader: An Update.

    Science.gov (United States)

    Perkins, Pamela

    A study examined two 1989 basal reading series' (published by McGraw Hill and Holt) readiness/priming sequences in order to ascertain the theoretical bases of each and then compared the findings with those of an earlier study. All pages of the readiness/priming sequence student texts and workbooks of both basal reading series were analyzed using…

  8. The basal ganglia communicate with the cerebellum.

    Science.gov (United States)

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2010-05-01

    The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically separate and to perform distinct functional operations. We investigated whether there is any direct route for basal ganglia output to influence cerebellar function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence cerebellar function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated functional network. PMID:20404184

  9. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  10. Pervasive transcription: detecting functional RNAs in bacteria.

    Science.gov (United States)

    Lybecker, Meghan; Bilusic, Ivana; Raghavan, Rahul

    2014-01-01

    Pervasive, or genome-wide, transcription has been reported in all domains of life. In bacteria, most pervasive transcription occurs antisense to protein-coding transcripts, although recently a new class of pervasive RNAs was identified that originates from within annotated genes. Initially considered to be non-functional transcriptional noise, pervasive transcription is increasingly being recognized as important in regulating gene expression. The function of pervasive transcription is an extensively debated question in the field of transcriptomics and regulatory RNA biology. Here, we highlight the most recent contributions addressing the purpose of pervasive transcription in bacteria and discuss their implications.

  11. A Novel Basal Body Protein That Is a Polo-like Kinase Substrate Is Required for Basal Body Segregation and Flagellum Adhesion in Trypanosoma brucei.

    Science.gov (United States)

    Hu, Huiqing; Zhou, Qing; Li, Ziyin

    2015-10-01

    The Polo-like kinase (PLK) in Trypanosoma brucei plays multiple roles in basal body segregation, flagellum attachment, and cytokinesis. However, the mechanistic role of TbPLK remains elusive, mainly because most of its substrates are not known. Here, we report a new substrate of TbPLK, SPBB1, and its essential roles in T. brucei. SPBB1 was identified through yeast two-hybrid screening with the kinase-dead TbPLK as the bait. It interacts with TbPLK in vitro and in vivo, and is phosphorylated by TbPLK in vitro. SPBB1 localizes to both the mature basal body and the probasal body throughout the cell cycle, and co-localizes with TbPLK at the basal body during early cell cycle stages. RNAi against SPBB1 in procyclic trypanosomes inhibited basal body segregation, disrupted the new flagellum attachment zone filament, detached the new flagellum, and caused defective cytokinesis. Moreover, RNAi of SPBB1 confined TbPLK at the basal body and the bilobe structure, resulting in constitutive phosphorylation of TbCentrin2 at the bilobe. Altogether, these results identified a basal body protein as a TbPLK substrate and its essential role in promoting basal body segregation and flagellum attachment zone filament assembly for flagellum adhesion and cytokinesis initiation.

  12. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  13. TFE and Spt4/5 open and close the RNA polymerase clamp during the transcription cycle.

    Science.gov (United States)

    Schulz, Sarah; Gietl, Andreas; Smollett, Katherine; Tinnefeld, Philip; Werner, Finn; Grohmann, Dina

    2016-03-29

    Transcription is an intrinsically dynamic process and requires the coordinated interplay of RNA polymerases (RNAPs) with nucleic acids and transcription factors. Classical structural biology techniques have revealed detailed snapshots of a subset of conformational states of the RNAP as they exist in crystals. A detailed view of the conformational space sampled by the RNAP and the molecular mechanisms of the basal transcription factors E (TFE) and Spt4/5 through conformational constraints has remained elusive. We monitored the conformational changes of the flexible clamp of the RNAP by combining a fluorescently labeled recombinant 12-subunit RNAP system with single-molecule FRET measurements. We measured and compared the distances across the DNA binding channel of the archaeal RNAP. Our results show that the transition of the closed to the open initiation complex, which occurs concomitant with DNA melting, is coordinated with an opening of the RNAP clamp that is stimulated by TFE. We show that the clamp in elongation complexes is modulated by the nontemplate strand and by the processivity factor Spt4/5, both of which stimulate transcription processivity. Taken together, our results reveal an intricate network of interactions within transcription complexes between RNAP, transcription factors, and nucleic acids that allosterically modulate the RNAP during the transcription cycle.

  14. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)

    WangCuncheng

    1993-01-01

    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  15. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  16. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  17. Structural basis of transcription activation.

    Science.gov (United States)

    Feng, Yu; Zhang, Yu; Ebright, Richard H

    2016-06-10

    Class II transcription activators function by binding to a DNA site overlapping a core promoter and stimulating isomerization of an initial RNA polymerase (RNAP)-promoter closed complex into a catalytically competent RNAP-promoter open complex. Here, we report a 4.4 angstrom crystal structure of an intact bacterial class II transcription activation complex. The structure comprises Thermus thermophilus transcription activator protein TTHB099 (TAP) [homolog of Escherichia coli catabolite activator protein (CAP)], T. thermophilus RNAP σ(A) holoenzyme, a class II TAP-dependent promoter, and a ribotetranucleotide primer. The structure reveals the interactions between RNAP holoenzyme and DNA responsible for transcription initiation and reveals the interactions between TAP and RNAP holoenzyme responsible for transcription activation. The structure indicates that TAP stimulates isomerization through simple, adhesive, stabilizing protein-protein interactions with RNAP holoenzyme. PMID:27284196

  18. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam

    2014-03-01

    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  19. The many faces of basal cell carcinoma

    OpenAIRE

    Jackson, Robert

    1982-01-01

    Basal cell carcinoma is the most easily cured carcinoma, but because of the many forms it can take, and because it grows so slowly, it can be misdiagnosed or neglected. The author discusses its more common forms and etiologic considerations.

  20. Automatic basal slice detection for cardiac analysis

    Science.gov (United States)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  1. Archaeal Transcription: Function of an Alternative Transcription Factor B from Pyrococcus furiosus▿

    OpenAIRE

    Micorescu, Michael; Grünberg, Sebastian; Franke, Andreas; Cramer, Patrick; Thomm, Michael; Bartlett, Michael

    2007-01-01

    The genome of the hyperthermophile archaeon Pyrococcus furiosus encodes two transcription factor B (TFB) paralogs, one of which (TFB1) was previously characterized in transcription initiation. The second TFB (TFB2) is unusual in that it lacks recognizable homology to the archaeal TFB/eukaryotic TFIIB B-finger motif. TFB2 functions poorly in promoter-dependent transcription initiation, but photochemical cross-linking experiments indicated that the orientation and occupancy of transcription com...

  2. Structural and functional insight into TAF1-TAF7, a subcomplex of transcription factor II D

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Suparna; Lou, Xiaohua; Hwang, Peter; Rajashankar, Kanagalaghatta R.; Wang, Xiaoping; Gustafsson, Jan-Åke; Fletterick, Robert J.; Jacobson, Raymond H.; Webb, Paul [MDACC; (HMRI); (Cornell); (UCSF); (Houston)

    2014-07-01

    Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase II-mediated PIC before transcriptional initiation. Here, we report the 3D structure of a complex of yeast TAF1 with TAF7 at 2.9 Å resolution. The structure displays novel architecture and is characterized by a large predominantly hydrophobic heterodimer interface and extensive cofolding of TAF subunits. There are no obvious similarities between TAF1 and known histone acetyltransferases. Instead, the surface of the TAF1–TAF7 complex contains two prominent conserved surface pockets, one of which binds selectively to an inhibitory trimethylated histone H3 mark on Lys27 in a manner that is also regulated by phosphorylation at the neighboring H3 serine. Our findings could point toward novel roles for the TAF1–TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks.

  3. Evolutionary Consequences of DNA Methylation in a Basal Metazoan.

    Science.gov (United States)

    Dixon, Groves B; Bay, Line K; Matz, Mikhail V

    2016-09-01

    Gene body methylation (gbM) is an ancestral and widespread feature in Eukarya, yet its adaptive value and evolutionary implications remain unresolved. The occurrence of gbM within protein-coding sequences is particularly puzzling, because methylation causes cytosine hypermutability and hence is likely to produce deleterious amino acid substitutions. We investigate this enigma using an evolutionarily basal group of Metazoa, the stony corals (order Scleractinia, class Anthozoa, phylum Cnidaria). We show that patterns of coral gbM are similar to other invertebrate species, predicting wide and active transcription and slower sequence evolution. We also find a strong correlation between gbM and codon bias, resulting from systematic replacement of CpG bearing codons. We conclude that gbM has strong effects on codon evolution and speculate that this may influence establishment of optimal codons. PMID:27189563

  4. Somatotopic organization of the primate basal ganglia

    Directory of Open Access Journals (Sweden)

    Atsushi eNambu

    2011-04-01

    Full Text Available Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson’s disease and dystonia.

  5. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

    2006-11-15

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  6. GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy.

    Science.gov (United States)

    Kuschal, Christiane; Botta, Elena; Orioli, Donata; Digiovanna, John J; Seneca, Sara; Keymolen, Kathelijn; Tamura, Deborah; Heller, Elizabeth; Khan, Sikandar G; Caligiuri, Giuseppina; Lanzafame, Manuela; Nardo, Tiziana; Ricotti, Roberta; Peverali, Fiorenzo A; Stephens, Robert; Zhao, Yongmei; Lehmann, Alan R; Baranello, Laura; Levens, David; Kraemer, Kenneth H; Stefanini, Miria

    2016-04-01

    The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEβ). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEα and TFIIEβ) as well as decreased phosphorylation of TFIIEα in cells from both children. Interestingly, decreased phosphorylation of TFIIEα was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP.

  7. GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy

    Science.gov (United States)

    Kuschal, Christiane; Botta, Elena; Orioli, Donata; Digiovanna, John J.; Seneca, Sara; Keymolen, Kathelijn; Tamura, Deborah; Heller, Elizabeth; Khan, Sikandar G.; Caligiuri, Giuseppina; Lanzafame, Manuela; Nardo, Tiziana; Ricotti, Roberta; Peverali, Fiorenzo A.; Stephens, Robert; Zhao, Yongmei; Lehmann, Alan R.; Baranello, Laura; Levens, David; Kraemer, Kenneth H.; Stefanini, Miria

    2016-01-01

    The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEβ). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEα and TFIIEβ) as well as decreased phosphorylation of TFIIEα in cells from both children. Interestingly, decreased phosphorylation of TFIIEα was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP. PMID:26996949

  8. GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy.

    Science.gov (United States)

    Kuschal, Christiane; Botta, Elena; Orioli, Donata; Digiovanna, John J; Seneca, Sara; Keymolen, Kathelijn; Tamura, Deborah; Heller, Elizabeth; Khan, Sikandar G; Caligiuri, Giuseppina; Lanzafame, Manuela; Nardo, Tiziana; Ricotti, Roberta; Peverali, Fiorenzo A; Stephens, Robert; Zhao, Yongmei; Lehmann, Alan R; Baranello, Laura; Levens, David; Kraemer, Kenneth H; Stefanini, Miria

    2016-04-01

    The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEβ). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEα and TFIIEβ) as well as decreased phosphorylation of TFIIEα in cells from both children. Interestingly, decreased phosphorylation of TFIIEα was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP. PMID:26996949

  9. The connectome of the basal ganglia.

    Science.gov (United States)

    Schmitt, Oliver; Eipert, Peter; Kettlitz, Richard; Leßmann, Felix; Wree, Andreas

    2016-03-01

    The basal ganglia of the laboratory rat consist of a few core regions that are specifically interconnected by efferents and afferents of the central nervous system. In nearly 800 reports of tract-tracing investigations the connectivity of the basal ganglia is documented. The readout of connectivity data and the collation of all the connections of these reports in a database allows to generate a connectome. The collation, curation and analysis of such a huge amount of connectivity data is a great challenge and has not been performed before (Bohland et al. PloS One 4:e7200, 2009) in large connectomics projects based on meta-analysis of tract-tracing studies. Here, the basal ganglia connectome of the rat has been generated and analyzed using the consistent cross-platform and generic framework neuroVIISAS. Several advances of this connectome meta-study have been made: the collation of laterality data, the network-analysis of connectivity strengths and the assignment of regions to a hierarchically organized terminology. The basal ganglia connectome offers differences in contralateral connectivity of motoric regions in contrast to other regions. A modularity analysis of the weighted and directed connectome produced a specific grouping of regions. This result indicates a correlation of structural and functional subsystems. As a new finding, significant reciprocal connections of specific network motifs in this connectome were detected. All three principal basal ganglia pathways (direct, indirect, hyperdirect) could be determined in the connectome. By identifying these pathways it was found that there exist many further equivalent pathways possessing the same length and mean connectivity weight as the principal pathways. Based on the connectome data it is unknown why an excitation pattern may prefer principal rather than other equivalent pathways. In addition to these new findings the local graph-theoretical features of regions of the connectome have been determined. By

  10. Radiologic study of basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1988-11-15

    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  11. Basal Cell Carcinoma in a Child

    OpenAIRE

    Samet Vasfi Kuvat; Zuhal Gücin; Barış Keklik; Gülzade Özyalvaçlı; Karaca Başaran

    2011-01-01

    Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period. An 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a 3 × 4 cm diameter on his posterior scalp. Macroscopically, the lesion was excised with a 10 mm safety margin. Pathologic examination revealed a basal cell carcinoma. No symptoms or signs of a syndrome were observed both in the patient and his family.

  12. The Sulfolobus initiator element is an important contributor to promoter strength.

    Science.gov (United States)

    Ao, Xiang; Li, Yingjun; Wang, Fan; Feng, Mingxia; Lin, Yanxu; Zhao, Shumiao; Liang, Yunxiang; Peng, Nan

    2013-11-01

    Basal elements in archaeal promoters, except for putative initiator elements encompassing transcription start sites, are well characterized. Here, we employed the Sulfolobus araS promoter as a model to study the function of the initiator element (Inr) in archaea. We have provided evidence for the presence of a third core promoter element, the Sulfolobus Inr, whose action depends on a TATA box and the TFB recognition element (BRE). Substitution mutations in the araS Inr did not alter the location of the transcription start site. Using systematic mutagenesis, the most functional araS Inr was defined as +1 GAGAMK +6 (where M is A/C and K is G/T). Furthermore, WebLogo analysis of a subset of promoters with coding sequences for 5' untranslated regions (UTRs) larger than 4 nucleotides (nt) in Sulfolobus solfataricus P2 identified an Inr consensus that exactly matches the functional araS Inr sequence. Moreover, mutagenesis of 3 randomly selected promoters confirmed the Inr sequences to be important for basal promoter strength in the subgroup. Importantly, the result of the araS Inr being added to the Inr-less promoters indicates that the araS Inr, the core promoter element, is able to enhance the strength of Inr-less promoters. We infer that transcription factor B (TFB) and subunits of RNA polymerase bind the Inr to enhance promoter strength. Taken together, our data suggest that the presence or absence of an Inr on basal promoters is important for global gene regulation in Sulfolobus. PMID:24039266

  13. Transcriptional directionality of the human insulin-degrading enzyme promoter.

    Science.gov (United States)

    Zhang, Lang; Wang, Pan; Ding, Qingyang; Wang, Zhao

    2013-10-01

    Unidirectional promoters dominate among mammalian genomes. However, the mechanism through which the transcriptional directionality of promoters is accomplished remains to be clarified. Insulin-degrading enzyme (IDE) is a ubiquitously expressed zinc metalloprotease, whose promoter contains a CpG island. We previously showed that the basal promoter region of mouse IDE has bidirectional transcriptional activity, but an upstream promoter element blocks its antisense transcription. Therefore, we wonder whether the human IDE promoter contains an analogous element. Similarly, the basal promoter region of human IDE (-102 ~ +173 and -196 ~ +173 relative to the transcription start site) showed bidirectional transcriptional activity. However, the region from -348 to +173 could only be transcribed from the normal orientation, implying that an upstream promoter element between -348 and -196 blocks the antisense transcription of the human IDE promoter. Through promoter deletion and mutagenesis analysis, we mapped this element precisely and found that the upstream promoter element locates between -318 and -304. Furthermore, the transcription-blocking elements in the mouse and human IDE promoters inhibited the transcription of the SV40 promoter when put downstream of it. In conclusion, we identify an upstream promoter element which blocks the antisense transcription of the human IDE promoter. Our studies are helpful to clarify the transcriptional directionality of promoters.

  14. Transcriptional interference by RNA polymerase pausing and dislodgement of transcription factors.

    Science.gov (United States)

    Palmer, Adam C; Egan, J Barry; Shearwin, Keith E

    2011-01-01

    Transcriptional interference is the in cis suppression of one transcriptional process by another. Mathematical modeling shows that promoter occlusion by elongating RNA polymerases cannot produce strong interference. Interference may instead be generated by (1) dislodgement of slow-to-assemble pre-initiation complexes and transcription factors and (2) prolonged occlusion by paused RNA polymerases.

  15. Basal ganglia orient eyes to reward.

    Science.gov (United States)

    Hikosaka, Okihide; Nakamura, Kae; Nakahara, Hiroyuki

    2006-02-01

    Expectation of reward motivates our behaviors and influences our decisions. Indeed, neuronal activity in many brain areas is modulated by expected reward. However, it is still unclear where and how the reward-dependent modulation of neuronal activity occurs and how the reward-modulated signal is transformed into motor outputs. Recent studies suggest an important role of the basal ganglia. Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly modulated by expected reward. Through their abundant outputs to the brain stem motor areas and the thalamocortical circuits, the basal ganglia appear capable of producing body movements based on expected reward. A good behavioral measure to test this hypothesis is saccadic eye movement because its brain stem mechanism has been extensively studied. Studies from our laboratory suggest that the basal ganglia play a key role in guiding the gaze to the location where reward is available. Neurons in the caudate nucleus and the substantia nigra pars reticulata are extremely sensitive to the positional difference in expected reward, which leads to a bias in excitability between the superior colliculi such that the saccade to the to-be-rewarded position occurs more quickly. It is suggested that the reward modulation occurs in the caudate where cortical inputs carrying spatial signals and dopaminergic inputs carrying reward-related signals are integrated. These data support a specific form of reinforcement learning theories, but also suggest further refinement of the theory.

  16. Reward functions of the basal ganglia.

    Science.gov (United States)

    Schultz, Wolfram

    2016-07-01

    Besides their fundamental movement function evidenced by Parkinsonian deficits, the basal ganglia are involved in processing closely linked non-motor, cognitive and reward information. This review describes the reward functions of three brain structures that are major components of the basal ganglia or are closely associated with the basal ganglia, namely midbrain dopamine neurons, pedunculopontine nucleus, and striatum (caudate nucleus, putamen, nucleus accumbens). Rewards are involved in learning (positive reinforcement), approach behavior, economic choices and positive emotions. The response of dopamine neurons to rewards consists of an early detection component and a subsequent reward component that reflects a prediction error in economic utility, but is unrelated to movement. Dopamine activations to non-rewarded or aversive stimuli reflect physical impact, but not punishment. Neurons in pedunculopontine nucleus project their axons to dopamine neurons and process sensory stimuli, movements and rewards and reward-predicting stimuli without coding outright reward prediction errors. Neurons in striatum, besides their pronounced movement relationships, process rewards irrespective of sensory and motor aspects, integrate reward information into movement activity, code the reward value of individual actions, change their reward-related activity during learning, and code own reward in social situations depending on whose action produces the reward. These data demonstrate a variety of well-characterized reward processes in specific basal ganglia nuclei consistent with an important function in non-motor aspects of motivated behavior. PMID:26838982

  17. Teaching Social Studies Using Basal Readers.

    Science.gov (United States)

    Garcia, Jesus; Logan, John W.

    1983-01-01

    A lesson, "Harriet Tubman: A Most Successful Conductor," illustrates how to employ a basal reader in social studies instruction in the elementary grades. This approach offers students a relevant curriculum, greater opportunities for concept development, practice in skills areas, and activities that offer greater opportunity to master social…

  18. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  19. Mitochondrial Transcription Factor B2 Is Essential for Metabolic Function in Drosophila melanogaster Development*

    OpenAIRE

    Adán, Cristina; Matsushima, Yuichi; Hernández-Sierra, Rosana; Marco-Ferreres, Raquel; Fernández-Moreno, Miguel Ángel; González-Vioque, Emiliano; Calleja, Manuel; Aragón, Juan J.; Kaguni, Laurie S.; Garesse, Rafael

    2008-01-01

    Characterization of the basal transcription machinery of mitochondrial DNA (mtDNA) is critical to understand mitochondrial pathophysiology. In mammalian in vitro systems, mtDNA transcription requires mtRNA polymerase, transcription factor A (TFAM), and either transcription factor B1 (TFB1M) or B2 (TFB2M). We have silenced the expression of TFB2M by RNA interference in Drosophila melanogaster. RNA interference knockdown of TF2BM causes lethality by arrest of larval deve...

  20. OOTFD (Object-Oriented Transcription Factors Database): an object-oriented successor to TFD.

    OpenAIRE

    Ghosh, D.

    1998-01-01

    ooTFD (object-oriented Transcription Factors Database) is a successor to TFD (Transcription Factors Database). ooTFD contains information represented in TFD but also allows the representation of containment, composite, and interaction relationships between transcription factor polypeptides. ooTFD is designed to represent information about all transcription factors, both eukaryotic and prokaryotic, basal as well as regulatory factors, and multiprotein complexes as well as monomers. ooTFD and a...

  1. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    OpenAIRE

    Sami N. Nasrallah; L. Raymond Reynolds

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism...

  2. Morphometric characteristics of basal cell carcinoma peritumoral stroma varies among basal cell carcinoma subtypes

    OpenAIRE

    Lesack Kyle; Naugler Christopher

    2012-01-01

    Abstract Background The role that the peritumoral stroma plays in the growth of tumours is currently poorly understood. In this manuscript the morphometric characteristics of basal cell carcinoma subtypes and their associated peritumoral stromas are presented. Methods Ninety eight digitized basal cell carcinoma histology slides were categorized as infiltrative, nodular, or superficial subtypes, and were analysed using a combination of manual and computer-assisted approaches. The morphometric ...

  3. Autogenous regulation of the EcoRII methylase gene at the transcriptional level: effect of 5-azacytidine.

    Science.gov (United States)

    Som, S; Friedman, S

    1993-01-01

    mRNA of the EcoRII methylase (M.EcoRII), a type II modification enzyme, was induced when Escherichia coli carrying a cloned M.EcoRII gene was exposed to the bacteriocidal drug 5-azacytidine. Induction occurred only when transcription was initiated from its own promoter. When the 5' promoter sequences were deleted or replaced with the lac promoter sequences, no induction occurred. The induction was independent of the template DNA level, but the presence of an intact M.EcoRII protein was a requirement. The drug is incorporated into DNA which then inhibits M.EcoRII by binding tightly to the enzyme. A deletion within the M.EcoRII coding region caused a marked increase in the basal level of mRNA transcribed from the M.EcoRII promoter, but no induction occurred upon 5-azacytidine treatment. The level could be reduced to normal by M.EcoRII in trans. In vitro, the enzyme bound to the sequences upstream of the transcription start sites and inhibited the initiation of transcription. These experiments indicate that expression of the M.EcoRII gene was autogenously regulated at the transcriptional level. Similar regulation is also noted in another DNA (cytosine-5) methylase, M.MspI. Images PMID:7693455

  4. Concentrated insulins: the new basal insulins

    OpenAIRE

    Lamos EM; Younk LM; Davis SN

    2016-01-01

    Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with in...

  5. Basal ganglia lesions in children and adults

    International Nuclear Information System (INIS)

    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive

  6. Basal cell carcinoma of the perineum

    OpenAIRE

    Levin, Adriane Ann; Dabade, Tushar; Dandekar, Monisha; Rogers, Gary; Rosmarin, David

    2014-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. Most BCCs are found on areas of UV-damaged skin, The study of BCCs of sun-protected regions, however, suggests a more complex pathogenesis. We present a case of BCC of the perineum in a man with no previous history of skin cancer. This is the first report of BCC in this region and one of a small body of cases arising on or near the genital and perianal regions.

  7. Linear Basal Cell Carcinoma: A Case Report

    OpenAIRE

    Ichinokawa, Yuko; Ohtuki, Akiko; Hattori, Mariko; Sadamasa, Hiroko; Hiruma, Masataro; Matumoto, Toshiharu

    2011-01-01

    Basal cell carcinoma (BCC) presents with diverse clinical features, and several morphologic and histologic variants of BCC have been reported [Sexton et al.: J Am Acad Dermatol 1990;23:1118-1126]. Linear BCC was first described as a new clinical subtype in 1985 by Lewis [Int J Dematol 1985;24:124-125]. Here, we present a case of linear BCC that we recently encountered in an elderly Japanese patient, and review other cases reported in Japan.

  8. Basal ganglia lesions in children and adults

    Energy Technology Data Exchange (ETDEWEB)

    Bekiesinska-Figatowska, Monika, E-mail: m.figatowska@mp.pl [Department of Diagnostic Imaging, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Mierzewska, Hanna, E-mail: h.mierzewska@gmail.com [Department of Neurology of Children and Adolescents, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Jurkiewicz, Elżbieta, E-mail: e-jurkiewicz@o2.pl [Department of Diagnostic Imaging, Children' s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw (Poland)

    2013-05-15

    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive.

  9. Basal ganglia lesions in children and adults.

    Science.gov (United States)

    Bekiesinska-Figatowska, Monika; Mierzewska, Hanna; Jurkiewicz, Elżbieta

    2013-05-01

    The term "basal ganglia" refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) - to a lesser degree - allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or - more frequently - bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic-ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive. PMID:23313708

  10. Structural insights into transcription complexes

    NARCIS (Netherlands)

    Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

    2011-01-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of st

  11. Basal cell carcinoma in oculo-cutaneous albinism

    OpenAIRE

    Ajay Kumar; Ashish Chauhan; Subhash Kashyap

    2016-01-01

    The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition ...

  12. Eukaryotic translation initiator protein 1A isoform, CCS-3, enhances the transcriptional repression of p21CIP1 by proto-oncogene FBI-1 (Pokemon/ZBTB7A).

    Science.gov (United States)

    Choi, Won-Il; Kim, Youngsoo; Kim, Yuri; Yu, Mi-young; Park, Jungeun; Lee, Choong-Eun; Jeon, Bu-Nam; Koh, Dong-In; Hur, Man-Wook

    2009-01-01

    FBI-1, a member of the POK (POZ and Kruppel) family of transcription factors, plays a role in differentiation, oncogenesis, and adipogenesis. eEF1A is a eukaryotic translation elongation factor involved in several cellular processes including embryogenesis, oncogenic transformation, cell proliferation, and cytoskeletal organization. CCS-3, a potential cervical cancer suppressor, is an isoform of eEF1A. We found that eEF1A forms a complex with FBI-1 by co-immunoprecipitation, SDS-PAGE, and MALDI-TOF Mass analysis of the immunoprecipitate. GST fusion protein pull-downs showed that FBI-1 directly interacts with eEF1A and CCS-3 via the zinc finger and POZ-domain of FBI-1. FBI-1 co-localizes with either eEF1A or CCS-3 at the nuclear periplasm. CCS-3 enhances transcriptional repression of the p21CIP1 gene (hereafter referred to as p21) by FBI-1. The POZ-domain of FBI-1 interacts with the co-repressors, SMRT and BCoR. We found that CCS-3 also interacts with the co-repressors independently. The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of FBI-1 appears to enhance FBI-1 mediated transcriptional repression. Our data suggest that CCS-3 may be important in cell differentiation, tumorigenesis, and oncogenesis by interacting with the proto-oncogene FBI-1 and transcriptional co-repressors. PMID:19471103

  13. Mössbauer spectroscopy of Basal Ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Miglierini, Marcel, E-mail: marcel.miglierini@stuba.sk [Institute of Nuclear and Physical Engineering, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovičova 3, 812 19 Bratislava, Slovakia and Regional Centre of Advanced Technologies and Materials (Czech Republic); Lančok, Adriana [Institute of Inorganic Chemistry AS CR, v. v. i., 250 68 Husinec-Řež 1001 (Czech Republic); Kopáni, Martin [Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Sasinkova 2, 811 08 Bratislava (Slovakia); Boča, Roman [Department of Chemistry, Faculty of Natural Sciences, University of SS. Cyril and Methodius, 917 01 Trnava (Slovakia)

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  14. Epidemiology of basal-like breast cancer

    OpenAIRE

    Millikan, Robert C.; Newman, Beth; Tse, Chiu-Kit; Moorman, Patricia G.; Conway, Kathleen; Smith, Lisa. V.; Labbok, Miriam H; Geradts, Joseph; Bensen, Jeannette T.; Jackson, Susan; Nyante, Sarah; Livasy, Chad; Carey, Lisa; Earp, H. Shelton; Perou, Charles M

    2007-01-01

    Risk factors for the newly identified “intrinsic” breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case–control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common s...

  15. Early Onset Basal Cell Carcinoma: Surgical Approach

    OpenAIRE

    Betekhtin M.; Ananiev J.; Tchernev G.; Zisova L.; Philipov S.; Hristova R.

    2014-01-01

    Basal cell carcinoma (BCC) is the most frequent non-melanoma skin cancer. Only 5-15% of BCC cases can be found in patients aged 20-40 years (so-called early onset). The early onset BCC is characterized by active and aggressive tumour growth, clinically presenting in most of the cases as a morpheaform, locally infiltrating or recurrent BCC. Despite the advances in the study of the pathogenesis of this tumour, surgery remains the most used, most effective and most suitable treatment modality. W...

  16. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC remains the most common form of nonmelanoma skin cancer (NMSC in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT, will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  17. Myosin light-chain phosphatase regulates basal actomyosin oscillations during morphogenesis.

    Science.gov (United States)

    Valencia-Expósito, Andrea; Grosheva, Inna; Míguez, David G; González-Reyes, Acaimo; Martín-Bermudo, María D

    2016-01-01

    Contractile actomyosin networks generate forces that drive tissue morphogenesis. Actomyosin contractility is controlled primarily by reversible phosphorylation of the myosin-II regulatory light chain through the action of myosin kinases and phosphatases. While the role of myosin light-chain kinase in regulating contractility during morphogenesis has been largely characterized, there is surprisingly little information on myosin light-chain phosphatase (MLCP) function in this context. Here, we use live imaging of Drosophila follicle cells combined with mathematical modelling to demonstrate that the MLCP subunit flapwing (flw) is a key regulator of basal myosin oscillations and cell contractions underlying egg chamber elongation. Flw expression decreases specifically on the basal side of follicle cells at the onset of contraction and flw controls the initiation and periodicity of basal actomyosin oscillations. Contrary to previous reports, basal F-actin pulsates similarly to myosin. Finally, we propose a quantitative model in which periodic basal actomyosin oscillations arise in a cell-autonomous fashion from intrinsic properties of motor assemblies.

  18. Management of the basal McMurray watersand during bitumen and heavy oil extraction

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, K.C. [CH2M Hill Canada Ltd., Calgary, AB (Canada)

    2002-07-01

    The risks associated with basal aquifers in steam-assisted gravity drainage (SAGD) recovery of heavy oils were discussed. Bitumen distribution within the McMurray Formation varies with facies changes in the deposit. The coarse-grained sand at the base of the formation forms a basal aquifer where the bitumen content is low and where pore pressures are high. The confined aquifer is very permeable which poses a major management issue for both open bit bitumen extraction and in situ heavy oil production. This is because the basal aquifer often requires depressurization, particularly in open pit mining because the high pore pressure can reduce pit wall stability. In addition, seepage to the pit floor can reduce the rate of traffic flow. Oilsand and basal aquifers, which provide the foundation for tailings ponds, can potentially form a groundwater flow path for pond seepage. One way to remedy this situation is to develop a strategy for wastewater injection into the basal aquifer, but before this is done certain issues must be addressed, including the effects of pressure interference, fracture initiation and related seepage. Other issues that must be addressed include the affect of increased discharge of poor quality insitu water into the Athabasca River.

  19. Human and murine prostate basal/stem cells are not direct targets of prolactin.

    Science.gov (United States)

    Sackmann-Sala, Lucila; Angelergues, Antoine; Boutillon, Florence; d'Acremont, Bruno; Maidenberg, Marc; Oudard, Stéphane; Goffin, Vincent

    2015-09-01

    Local overexpression of prolactin (PRL) in the prostate of Pb-PRL transgenic mice induces benign prostate tumors exhibiting marked amplification of the epithelial basal/stem cell compartment. However, PRL-activated intracellular signaling seems to be restricted to luminal cells, suggesting that basal/stem cells may not be direct targets of PRL. Given their described role as prostate cancer-initiating cells, it is important to understand the mechanisms that regulate basal/stem cells. In this study, we evaluated whether PRL can act directly on these cells, by growing them as prostaspheres. For this, primary 3D prostasphere cultures were prepared from unfractionated cells isolated from freshly harvested human and mouse benign prostate tissues and subjected to PRL stimulation in vitro. None of the various concentrations of PRL tested showed any effects on the sizes or numbers of the prostaspheres generated. In addition, neither activation of canonical PRL-induced signaling pathways (Stat5, Stat3 or Erk1/2) nor increased expression of the proliferation marker Ki-67 were detected by immunostaining in PRL-stimulated prostaspheres. Consistent with the absence of response, PRL receptor mRNA levels were generally undetectable in mouse sphere cells. We conclude that human and mouse prostate basal/stem cells are not direct targets of PRL action. The observed amplification of basal/stem cells in Pb-PRL prostates might be due to paracrine mechanisms originating from PRL action on other cell compartments. Our current efforts are aimed at unraveling these mechanisms.

  20. Evolution of sensory structures in basal metazoa.

    Science.gov (United States)

    Jacobs, Dave K; Nakanishi, Nagayasu; Yuan, David; Camara, Anthony; Nichols, Scott A; Hartenstein, Volker

    2007-11-01

    Cnidaria have traditionally been viewed as the most basal animals with complex, organ-like multicellular structures dedicated to sensory perception. However, sponges also have a surprising range of the genes required for sensory and neural functions in Bilateria. Here, we: (1) discuss "sense organ" regulatory genes, including; sine oculis, Brain 3, and eyes absent, that are expressed in cnidarian sense organs; (2) assess the sensory features of the planula, polyp, and medusa life-history stages of Cnidaria; and (3) discuss physiological and molecular data that suggest sensory and "neural" processes in sponges. We then develop arguments explaining the shared aspects of developmental regulation across sense organs and between sense organs and other structures. We focus on explanations involving divergent evolution from a common ancestral condition. In Bilateria, distinct sense-organ types share components of developmental-gene regulation. These regulators are also present in basal metazoans, suggesting evolution of multiple bilaterian organs from fewer antecedent sensory structures in a metazoan ancestor. More broadly, we hypothesize that developmental genetic similarities between sense organs and appendages may reflect descent from closely associated structures, or a composite organ, in the common ancestor of Cnidaria and Bilateria, and we argue that such similarities between bilaterian sense organs and kidneys may derive from a multifunctional aggregations of choanocyte-like cells in a metazoan ancestor. We hope these speculative arguments presented here will stimulate further discussion of these and related questions. PMID:21669752

  1. MADS-box gene evolution-structure and transcription patterns

    DEFF Research Database (Denmark)

    Johansen, Bo; Pedersen, Louise B; Skipper, Martin;

    2002-01-01

    from earlier analyses, and all major monophyletic groups are further supported by a common gene structure in exons 1-6 and by conserved C-terminal motifs. Transcription patterns are mapped on the tree to obtain an overview of MIKC gene transcription. Genes that are transcribed only in vegetative organs...... are located in the basal part of the tree, whereas genes involved in flower development have evolved later. As the universality of the ABC model has recently been questioned, special account is paid to the expression of A-, B-, and C-class genes. Mapping of transcription patterns on the phylogeny shows all...

  2. Conserved interaction of the papillomavirus E2 transcriptional activator proteins with human and yeast TFIIB proteins.

    OpenAIRE

    Benson, J D; Lawande, R; Howley, P M

    1997-01-01

    Papillomavirus early gene expression is regulated by the virus gene-encoded E2 proteins. The best-characterized E2 protein, encoded by bovine papillomavirus type 1 (BPV-1), has been shown to interact with basal transcription factor IIB (TFIIB) and the TATA binding protein basal transcription factor (N. M. Rank and P. F. Lambert, J. Virol. 69:6323-6334, 1995). We demonstrate that the potent E2 transcriptional activator protein encoded by a gene of human PV type 16 also interacts with TFIIB in ...

  3. Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Mackler, Randi M; Livasy, Chad A; Coleman, William B

    2014-02-01

    Basal-like breast cancers frequently express aberrant DNA hypermethylation associated with concurrent silencing of specific genes secondary to DNMT3b overexpression and DNMT hyperactivity. DNMT3b is known to be post-transcriptionally regulated by microRNAs. The objective of the current study was to determine the role of microRNA dysregulation in the molecular mechanism governing DNMT3b overexpression in primary breast cancers that express aberrant DNA hypermethylation. The expression of microRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a and miR-148b) or are predicted to regulate DNMT3b (miR‑26a, miR-26b, miR-203 and miR-222) were evaluated among 70 primary breast cancers (36 luminal A-like, 13 luminal B-like, 5 HER2‑enriched, 16 basal-like) and 18 normal mammoplasty tissues. Significantly reduced expression of miR-29c distinguished basal-like breast cancers from other breast cancer molecular subtypes. The expression of aberrant DNA hypermethylation was determined in a subset of 33 breast cancers (6 luminal A-like, 6 luminal B-like, 5 HER2-enriched and 16 basal-like) through examination of methylation‑sensitive biomarker gene expression (CEACAM6, CDH1, CST6, ESR1, GNA11, MUC1, MYB, TFF3 and SCNN1A), 11/33 (33%) cancers exhibited aberrant DNA hypermethylation including 9/16 (56%) basal-like cancers, but only 2/17 (12%) non-basal-like cancers (luminal A-like, n=1; HER2-enriched, n=1). Breast cancers with aberrant DNA hypermethylation express diminished levels of miR-29a, miR-29b, miR-26a, miR-26b, miR-148a and miR-148b compared to cancers lacking aberrant DNA hypermethylation. A total of 7/9 (78%) basal-like breast cancers with aberrant DNA hypermethylation exhibit diminished levels of ≥6 regulatory miRs. The results show that i) reduced expression of miR-29c is characteristic of basal-like breast cancers, ii) miR and methylation-sensitive gene expression patterns identify two subsets of basal-like breast cancers, and iii) the subset of basal

  4. Basal area from photos.... Is it possible?

    Science.gov (United States)

    Sparrow, B.; Ward, B.; Armston, J.; Schaefer, M.; Thurgate, N.; van den Hengel, A.; Lowe, A.; Phinn, S. R.

    2013-12-01

    This paper describes collaborative work conducted between the Ausplots and AusCover facilities within Australia's Terrestrial Ecosystem Research Network (TERN) and the Australian Centre for Visual Technologies (ACVT) to develop new photopoint collection methodologies for use by terrestrial ecologists. These photopoints are being collected at Ausplots survey sites throughout rangeland environments across Australia along with a wide suite of environmental measures, including a range of soil, vegetation species and structure and genetics information, with currently around 270 sites out of 700 collected. These collections are intended to augment the ecological data collected at each site and provide a record of that time. Similar measures are also being collected at Auscover calibration and validation sites. Our photopoints incorporate three sets of overlapping photographs, each collected from exposure points at the vertices of an equilateral triangle with sides of 2.5 m located around the centre point of the field site. The photos from each exposure point typically overlap by 50% and at least one photo in each series include a calibration target mounted on a pole at the centre of the exposure points. These photographs are then processed to create a range of data products. Seamless photo panoramas are constructed for each field site and are stored with the relevant site data allowing ecologists utilising the ecological data to also include the environment in which that data were collected. Point clouds are also produced allowing a three dimensional view of the site and potentially allowing similar analysis, albeit at lower precision, to that of terrestrial Lidar systems. These three dimensional site reconstructions are used to measure stem diameters, and calculate basal area, which are summed for the site, providing a measure of basal area per hectare when the visible distance is taken into account. This method is potentially more accurate than rapid techniques such as

  5. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, Ontario (Canada)

    2006-04-15

    Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

  6. Full transcription of the chloroplast genome in photosynthetic eukaryotes.

    Science.gov (United States)

    Shi, Chao; Wang, Shuo; Xia, En-Hua; Jiang, Jian-Jun; Zeng, Fan-Chun; Gao, Li-Zhi

    2016-01-01

    Prokaryotes possess a simple genome transcription system that is different from that of eukaryotes. In chloroplasts (plastids), it is believed that the prokaryotic gene transcription features govern genome transcription. However, the polycistronic operon transcription model cannot account for all the chloroplast genome (plastome) transcription products at whole-genome level, especially regarding various RNA isoforms. By systematically analyzing transcriptomes of plastids of algae and higher plants, and cyanobacteria, we find that the entire plastome is transcribed in photosynthetic green plants, and that this pattern originated from prokaryotic cyanobacteria - ancestor of the chloroplast genomes that diverged about 1 billion years ago. We propose a multiple arrangement transcription model that multiple transcription initiations and terminations combine haphazardly to accomplish the genome transcription followed by subsequent RNA processing events, which explains the full chloroplast genome transcription phenomenon and numerous functional and/or aberrant pre-RNAs. Our findings indicate a complex prokaryotic genome regulation when processing primary transcripts. PMID:27456469

  7. Transcription Termination: Variations on Common Themes.

    Science.gov (United States)

    Porrua, Odil; Boudvillain, Marc; Libri, Domenico

    2016-08-01

    Transcription initiates pervasively in all organisms, which challenges the notion that the information to be expressed is selected mainly based on mechanisms defining where and when transcription is started. Together with post-transcriptional events, termination of transcription is essential for sorting out the functional RNAs from a plethora of transcriptional products that seemingly have no use in the cell. But terminating transcription is not that easy, given the high robustness of the elongation process. We review here many of the strategies that prokaryotic and eukaryotic cells have adopted to dismantle the elongation complex in a timely and efficient manner. We highlight similarities and diversity, underlying the existence of common principles in a diverse set of functionally convergent solutions. PMID:27371117

  8. Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

    Directory of Open Access Journals (Sweden)

    Sarah Phillips

    2014-05-01

    Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

  9. Early Onset Basal Cell Carcinoma: Surgical Approach

    Directory of Open Access Journals (Sweden)

    Betekhtin M.

    2014-06-01

    Full Text Available Basal cell carcinoma (BCC is the most frequent non-melanoma skin cancer. Only 5-15% of BCC cases can be found in patients aged 20-40 years (so-called early onset. The early onset BCC is characterized by active and aggressive tumour growth, clinically presenting in most of the cases as a morpheaform, locally infiltrating or recurrent BCC. Despite the advances in the study of the pathogenesis of this tumour, surgery remains the most used, most effective and most suitable treatment modality. We describe a case of a 39-year-old woman who developed an early onset BCC of the nasolabial fold. After the subsequent surgical excision an excellent cosmetic result was achieved.

  10. Basal Cell Nevus Syndrome. A Case Presentation

    Directory of Open Access Journals (Sweden)

    Ángel Luis Cruz Leiva

    2007-12-01

    Full Text Available Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

  11. (p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter crescentus in response to a block in lipid biosynthesis.

    Science.gov (United States)

    Stott, Kristina V; Wood, Shannon M; Blair, Jimmy A; Nguyen, Bao T; Herrera, Anabel; Mora, Yannet G Perez; Cuajungco, Math P; Murray, Sean R

    2015-03-01

    Stress conditions, such as a block in fatty acid synthesis, signal bacterial cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle-regulated β-ketoacyl-acyl carrier protein synthase that initiates lipid biosynthesis and is essential for growth in rich media. To explore how C. crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion strain. We found that FabH depletion blocks lipid biosynthesis in rich media and causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation. Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and a block in the over-initiation of DNA replication in response to FabH depletion. The gene ctrA encodes a master transcription factor that directly regulates 95 cell-cycle-controlled genes while also functioning to inhibit the initiation of DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp-dependent during fatty acid starvation. CtrA fails to accumulate when FabH is depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during fatty acid starvation initiated from only one of the two ctrA promoters. In the absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non-culturable state, with multiple chromosomes, and are unable to recover from the miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate C. crescentus' re-entry into the cell cycle after termination of fatty acid starvation.

  12. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  13. Over-represented localized sequence motifs in ribosomal protein gene promoters of basal metazoans.

    Science.gov (United States)

    Perina, Drago; Korolija, Marina; Roller, Maša; Harcet, Matija; Jeličić, Branka; Mikoč, Andreja; Cetković, Helena

    2011-07-01

    Equimolecular presence of ribosomal proteins (RPs) in the cell is needed for ribosome assembly and is achieved by synchronized expression of ribosomal protein genes (RPGs) with promoters of similar strengths. Over-represented motifs of RPG promoter regions are identified as targets for specific transcription factors. Unlike RPs, those motifs are not conserved between mammals, drosophila, and yeast. We analyzed RPGs proximal promoter regions of three basal metazoans with sequenced genomes: sponge, cnidarian, and placozoan and found common features, such as 5'-terminal oligopyrimidine tracts and TATA-boxes. Furthermore, we identified over-represented motifs, some of which displayed the highest similarity to motifs abundant in human RPG promoters and not present in Drosophila or yeast. Our results indicate that humans over-represented motifs, as well as corresponding domains of transcription factors, were established very early in metazoan evolution. The fast evolving nature of RPGs regulatory network leads to formation of other, lineage specific, over-represented motifs. PMID:21457775

  14. Basal Transcription Factor 3 Plays an Important Role in Seed Germination and Seedling Growth of Rice

    Directory of Open Access Journals (Sweden)

    Wenyi Wang

    2014-01-01

    Full Text Available BTF3 has been recognized to be involved in plant growth and development. But its function remains mostly unknown during seed germination and seedling stage. Here, we have analyzed OsBTF3-related sequences in Oryza sativa L. subspecies, japonica, which resembles with the conserved domain of a nascent polypeptide associated complex (NAC with different homologs of OsBTF3 and human BTF3. Inhibition of Osj10gBTF3 has led to considerable morphological changes during seed germination and seedling growth. Germination percentage was not influenced by the application of GA3, ABA, and NaCl but all concentrations caused wild-type (WT seeds to germinate more rapidly than the RNAi (Osj10gBTF3Ri transgenic lines. Seedling inhibition was more severe in the Osj10gBTF3Ri seedlings compared with their WT especially when treated with 100 or 200 μM GA3; 50% reduction in shoots was observed in Osj10gBTF3Ri seedlings. The expression of Osj3g1BTF3, Osj3g2BTF3 and Osj10gBTF3 was primarily constitutive and generally modulated by NaCl, ABA, and GA3 stresses in both Osj10gBTF3Ri lines and WT at the early seedling stage, suggesting that Osj3g1BTF3 and Osj10gBTF3 are much similar but different from Osj3g2BTF3 in biological function. These results show that OsBTF3 plays an important role in seed germination and seedling growth gives a new perception demonstrating that more multifaceted regulatory functions are linked with BTF3 in plants.

  15. Basal Transcription Factor 3 Plays an Important Role in Seed Germination and Seedling Growth of Rice

    OpenAIRE

    Wenyi Wang; Mengyun Xu; Ya Wang; Muhammad Jamil

    2014-01-01

    BTF3 has been recognized to be involved in plant growth and development. But its function remains mostly unknown during seed germination and seedling stage. Here, we have analyzed OsBTF3-related sequences in Oryza sativa L. subspecies, japonica, which resembles with the conserved domain of a nascent polypeptide associated complex (NAC) with different homologs of OsBTF3 and human BTF3. Inhibition of Osj10gBTF3 has led to considerable morphological changes during seed germination and seedling g...

  16. Mouse model for the DNA repair/basal transcription disorder Trichothiodystrophy reveals cancer predisposition.

    NARCIS (Netherlands)

    J. de Boer (Jan); H. van Steeg (Harry); R.J.W. Berg (Rob); J. Garssen (Johan); J. de Wit (Jan); C.T.M. van Oostrom (Conny); R.B. Beems (Rudolf); G.T.J. van der Horst (Gijsbertus); C.F. van Kreijl (Coen); F.R. de Gruijl (Frank); D. Bootsma (Dirk); J.H.J. Hoeijmakers (Jan); G. Weeda (Geert)

    1999-01-01

    textabstractPatients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient trichothiodystrophy (TTD) patients carrying mutations in the same XPD gene. XPD en

  17. Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition

    NARCIS (Netherlands)

    J. de Boer (Jan); C.F. van Kreijl (Coen); G. Weeda (Geert); F.R. de Gruijl (Frank); D. Bootsma (Dirk); H. van Steeg (Harry); R.J.W. Berg (Rob); J. Garssen (Johan); J. de Wit (Jan); C.T. van Oostrum; R.B. Beems (Rudolf); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus)

    1999-01-01

    textabstractPatients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient trichothiodystrophy (TTD) patients carrying mutations in the sam

  18. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    OpenAIRE

    Lee, Jong-Sun; Park, Jin; Kim, Seong-min; Yun, Seok-Kweon; Kim, Han-Uk

    2009-01-01

    Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area.

  19. Sequence learning in a model of the basal ganglia

    OpenAIRE

    Søiland, Stian

    2006-01-01

    This thesis presents a computational model of the basal ganglia that is able to learn sequences and perform action selection. The basal ganglia is a set of structures in the human brain involved in everything from action selection to reinforcement learning, inspiring research in psychology, neuroscience and computer science. Two temporal difference models of the basal ganglia based on previous work have been reimplemented. Several experiments and analyses help understand and describe the or...

  20. Covert skill learning in a cortical-basal ganglia circuit

    OpenAIRE

    Charlesworth, JD; Warren, TL; Brainard, MS

    2012-01-01

    We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning; influential ' actor-models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire. Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit, contributes to s...

  1. PIGMENTED BASAL CELL CARCINOMA: A RARE CLINICAL AND HISTOPATHOLOGICAL VARIANT

    OpenAIRE

    Chandralekha; Vijaya Bhaskar; Bhagyalakshmi; Sudhakar; Sumanlatha

    2015-01-01

    Basal cell carcinoma is a common malignant tumour of skin , commonly referred to as „rodent ulcer‟. It is common in the head and neck region. Exposure to ultraviolet radiation is an important risk factor. Pigmented basal cell carcinoma is a clinical and histological variant of basal cell carcinoma that exhibits inc reased pigmentation. It is a rare variant that can clinically mimic malignant melanoma. It is more common in males than females. Herein , we are...

  2. Transcription by Methanothermobacter thermautotrophicus RNA Polymerase In Vitro Releases Archaeal Transcription Factor B but Not TATA-Box Binding Protein from the Template DNA

    OpenAIRE

    Xie, Yunwei; Reeve, John N.

    2004-01-01

    Transcription initiation in Archaea requires the assembly of a preinitiation complex containing the TATA- box binding protein (TBP), transcription factor B (TFB), and RNA polymerase (RNAP). The results reported establish the fate of Methanothermobacter thermautotrophicus TBP and TFB following transcription initiation by M. thermautotrophicus RNAP in vitro. TFB is released after initiation, during extension of the transcript from 4 to 24 nucleotides, but TBP remains bound to the template DNA. ...

  3. Basal cell carcinoma in oculo-cutaneous albinism

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-06-01

    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

  4. Giant Basal Cell Carcinoma of the Forehead: A Case Report

    OpenAIRE

    Rudić, Milan; Kranjčec, Zoran; Lisica-Šikić, Nataša; Kovačić, Marijan

    2012-01-01

    Giant basal cell carcinoma (GBCC) is defined as a tumor 5cm or greater in diameter. They present less than 1% of all basal cell carcinomas. We present a case of an 85-year-old male patient with a giant ulcerating tumor of the left forehead (measuring 7x6cm). Under local anesthesia tumor was surgically excised. No involvement of the underlying periostal or bone structure was noted. Pathohystological exam revealed the giant basal cell carcinoma, with free surgical margins. Giant basal cell carc...

  5. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Science.gov (United States)

    Nasrallah, Sami N; Reynolds, L Raymond

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual.4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety.5. PMID:22879797

  6. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    Lo Muzio Lorenzo

    2008-11-01

    Full Text Available Abstract Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs, odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies. Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling. Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome. Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser

  7. Signaling mechanisms and behavioral function of the mouse basal vomeronasal neuroepithelium

    OpenAIRE

    Pablo Chamero

    2014-01-01

    The vomeronasal organ (VNO) is a sensory organ that is found in most terrestrial vertebrates and that is principally implicated in the detection of pheromones. The VNO contains specialized sensory neurons organized in a pseudostratified neuroepithelium that recognize chemical signals involved in initiating innate behavioral responses. In rodents, the VNO neuroepithelium is segregated into two distinct zones, apical and basal. The molecular mechanisms involved in ligand detection by apical and...

  8. Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis Shows that WhiB Is a Transcription Factor That Cocontrols Its Regulon with WhiA To Initiate Developmental Cell Division in Streptomyces

    Directory of Open Access Journals (Sweden)

    Matthew J. Bush

    2016-04-01

    Full Text Available WhiB is the founding member of a family of proteins (the WhiB-like [Wbl] family that carry a [4Fe-4S] iron-sulfur cluster and play key roles in diverse aspects of the biology of actinomycetes, including pathogenesis, antibiotic resistance, and the control of development. In Streptomyces, WhiB is essential for the process of developmentally controlled cell division that leads to sporulation. The biochemical function of Wbl proteins has been controversial; here, we set out to determine unambiguously if WhiB functions as a transcription factor using chromatin immunoprecipitation sequencing (ChIP-seq in Streptomyces venezuelae. In the first demonstration of in vivo genome-wide Wbl binding, we showed that WhiB regulates the expression of key genes required for sporulation by binding upstream of ~240 transcription units. Strikingly, the WhiB regulon is identical to the previously characterized WhiA regulon, providing an explanation for the identical phenotypes of whiA and whiB mutants. Using ChIP-seq, we demonstrated that in vivo DNA binding by WhiA depends on WhiB and vice versa, showing that WhiA and WhiB function cooperatively to control expression of a common set of WhiAB target genes. Finally, we show that mutation of the cysteine residues that coordinate the [4Fe-4S] cluster in WhiB prevents DNA binding by both WhiB and WhiA in vivo.

  9. Fluctuating selection on basal metabolic rate.

    Science.gov (United States)

    Nilsson, Johan F; Nilsson, Jan-Åke

    2016-02-01

    BMR (Basal metabolic rate) is an important trait in animal life history as it represents a significant part of animal energy budgets. BMR has also been shown to be positively related to sustainable work rate and maximal thermoregulatory capacity. To this date, most of the studies have focused on the causes of interspecific and intraspecific variation in BMR, and fairly little is known about the fitness consequences of different metabolic strategies. In this study, we show that winter BMR affects local survival in a population of wild blue tits (Cyanistes caeruleus), but that the selection direction differs between years. We argue that this fluctuating selection is probably a consequence of varying winter climate with a positive relation between survival and BMR during cold and harsh conditions, but a negative relation during mild winters. This fluctuating selection can not only explain the pronounced variation in BMR in wild populations, but will also give us new insights into how energy turnover rates can shape the life-history strategies of animals. Furthermore, the study shows that the process of global warming may cause directional selection for a general reduction in BMR, affecting the general life-history strategy on the population level. PMID:26839687

  10. In Vitro Transcription Assays and Their Application in Drug Discovery.

    Science.gov (United States)

    Yang, Xiao; Ma, Cong

    2016-09-20

    In vitro transcription assays have been developed and widely used for many years to study the molecular mechanisms involved in transcription. This process requires multi-subunit DNA-dependent RNA polymerase (RNAP) and a series of transcription factors that act to modulate the activity of RNAP during gene expression. Sequencing gel electrophoresis of radiolabeled transcripts is used to provide detailed mechanistic information on how transcription proceeds and what parameters can affect it. In this paper we describe the protocol to study how the essential elongation factor NusA regulates transcriptional pausing, as well as a method to identify an antibacterial agent targeting transcription initiation through inhibition of RNAP holoenzyme formation. These methods can be used a as platform for the development of additional approaches to explore the mechanism of action of the transcription factors which still remain unclear, as well as new antibacterial agents targeting transcription which is an underutilized drug target in antibiotic research and development.

  11. Correlating chemical sensitivity and basal gene expression reveals mechanism of action

    Science.gov (United States)

    Rees, Matthew G.; Seashore-Ludlow, Brinton; Cheah, Jaime H.; Adams, Drew J.; Price, Edmund V.; Gill, Shubhroz; Javaid, Sarah; Coletti, Matthew E.; Jones, Victor L.; Bodycombe, Nicole E.; Soule, Christian K.; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D.; Hon, C. Suk-Yee; Munoz, Benito; Liefeld, Ted; Dančík, Vlado; Haber, Daniel A.; Clish, Clary B.; Bittker, Joshua A.; Palmer, Michelle; Wagner, Bridget K.; Clemons, Paul A.; Shamji, Alykhan F.; Schreiber, Stuart L.

    2015-01-01

    Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ~19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters, and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal. PMID:26656090

  12. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.

    Science.gov (United States)

    Tadokoro, Tomomi; Gao, Xia; Hong, Charles C; Hotten, Danielle; Hogan, Brigid L M

    2016-03-01

    The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID:26811382

  13. Methanobacterium thermoautotrophicum RNA Polymerase and Transcription In Vitro

    OpenAIRE

    Darcy, Trevor J.; Hausner, Winfried; Awery, Donald E.; Edwards, Aled M.; Thomm, Michael; Reeve, John N.

    1999-01-01

    RNA polymerase (RNAP) purified from Methanobacterium thermoautotrophicum ΔH has been shown to initiate transcription accurately in vitro from the hmtB archaeal histone promoter with either native or recombinant forms of the M. thermoautotrophicum TATA-binding protein and transcription factor TFB. Efforts to obtain transcription initiation from hydrogen-regulated methane gene promoters were, however, unsuccessful. Two previously unrecognized archaeal RNAP subunits have been identified, and com...

  14. Nucleic Acid Analogue Induced Transcription of Double Stranded DNA

    DEFF Research Database (Denmark)

    1998-01-01

    RNA is transcribed from a double stranded DNA template by forming a complex by hybridizing to the template at a desired transcription initiation site one or more oligonucleic acid analogues of the PNA type capable of forming a transcription initiation site with the DNA and exposing the complex to...... displacement of one strand of the DNA locally by the PNA hybridization....

  15. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

    Science.gov (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-07-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

  16. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

    Science.gov (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-07-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.

  17. Basal cell hyperplasia and basal cell carcinoma of the prostate: a comprehensive review and discussion of a case with c-erbB-2 expression

    OpenAIRE

    Montironi, R; Mazzucchelli, R; Stramazzotti, D; Scarpelli, M; López Beltran, A; Bostwick, D. G.

    2005-01-01

    Prostatic basal cell proliferations range from ordinary basal cell hyperplasia (BCH) to florid basal cell hyperplasia to basal cell carcinoma. The distinction between these forms of BCH, including the variant with prominent nucleoli (formerly called atypical BCH), and basal cell carcinoma depends on morphological and immunohistochemical criteria and, in particular, on the degree of cell proliferation. In florid BCH, the proliferation index is intermediate between ordinary BCH and basal cell c...

  18. Genetics Home Reference: familial idiopathic basal ganglia calcification

    Science.gov (United States)

    ... Wang QK, Liu JY. Identification of a novel genetic locus on chromosome 8p21.1-q11.23 for idiopathic ... DH. Analysis of candidate genes at the IBGC1 locus associated with idiopathic basal ... DH. Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr ...

  19. The Place of Career Women in the Basals.

    Science.gov (United States)

    Leondis, Mary T.

    A study analyzed two basal reading series to determine if they depicted realistically the role of the career woman as she exists in society. A list of female careers in the 1989 editions of Houghton-Mifflin and McGraw Hill reading basals for grades 1 to 6 was compared to the career categories of the "United States Bureau of Census, Statistical…

  20. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    Science.gov (United States)

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  1. Mineralizing angiopathy with basal ganglia stroke in an infant

    Directory of Open Access Journals (Sweden)

    Puneet Jain

    2015-01-01

    Full Text Available Basal ganglia stroke is known following trivial head trauma. Recently a distinct clinic-radiological entity termed ′mineralizing angiopathy′ was described. We report an infant who developed basal ganglia stroke following trivial fall. His clinic-radiological features are described.

  2. Basal ganglia outputs map instantaneous position coordinates during behavior.

    Science.gov (United States)

    Barter, Joseph W; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A; Bartholomew, Ryan A; Yin, Henry H

    2015-02-11

    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions.

  3. Basal ganglia - thalamus and the crowning enigma

    Directory of Open Access Journals (Sweden)

    Marianela eGarcia-Munoz

    2015-11-01

    Full Text Available When Hubel (1982 referred to layer 1 of primary visual cortex as …a ‘crowning mystery’ to keep area-17 physiologists busy for years to come... he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1, the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory cortex before focusing on motor cortex.

  4. Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma?

    OpenAIRE

    Mehta, Karaninder S.; Mahajan, Vikram K.; Pushpinder S Chauhan; Anju Lath Sharma; Vikas Sharma; Abhinav, C.; Gayatri Khatri; Neel Prabha; Saurabh Sharma; Muninder Negi

    2012-01-01

    Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide s...

  5. Our evolving knowledge of the transcriptional landscape.

    Science.gov (United States)

    Hume, David A

    2008-01-01

    The development of a genome-scale approach to identification of the 5' ends of capped mRNAs (CAGE) has given new insights into many aspects of mammalian RNApolII transcription control. They include the identification of the minimal initiator motif, the different types of proximal promoter architecture, the promoters of noncoding RNAs, the transcription of retrotransposons, and the extensive impact of alternative promoters on the proteome. CAGE also offers applications as a form of expression profiling that measures promoter use, allowing more precise development of transcriptional network models.

  6. CHD chromatin remodelers and the transcription cycle.

    Science.gov (United States)

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  7. Basal forebrain projections to the lateral habenula modulate aggression reward.

    Science.gov (United States)

    Golden, Sam A; Heshmati, Mitra; Flanigan, Meghan; Christoffel, Daniel J; Guise, Kevin; Pfau, Madeline L; Aleyasin, Hossein; Menard, Caroline; Zhang, Hongxing; Hodes, Georgia E; Bregman, Dana; Khibnik, Lena; Tai, Jonathan; Rebusi, Nicole; Krawitz, Brian; Chaudhury, Dipesh; Walsh, Jessica J; Han, Ming-Hu; Shapiro, Matt L; Russo, Scott J

    2016-06-30

    Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing. PMID:27357796

  8. Genetic and epigenetic control of RKIP transcription.

    Science.gov (United States)

    Datar, Ila; Tegegne, Hanna; Qin, Kevin; Al-Mulla, Fahd; Bitar, Milad S; Trumbly, Robert J; Yeung, Kam C

    2014-01-01

    Raf kinase inhibitory protein (RKIP) is known to modulate key signaling cascades and regulate normal physiological processes such as cellular proliferation, differentiation, and apoptosis. The expression of RKIP is found to be downregulated in several cancer metastases and the repressed RKIP expression can be reactivated on treatment with chemotherapeutic agents. RKIP is a proven tumor metastasis suppressor gene and investigating the mechanisms of transcriptional regulation of RKIP is therefore of immense clinical importance. In this review, we discuss the basal expression of RKIP in various tissues and the genetic aspects of the RKIP chromosomal locus including the structure of the RKIP promoter as well as gene regulatory elements such as enhancers. We also review the genetic and epigenetic modulation of RKIP transcription through EZH2, a component of the polycomb repressive complex 2 (PRC2) and sequence specific transcription factors (TFs) BACH1 and Snail. Emerging experimental evidence supports a unifying model in which both these TFs repress RKIP transcription in cancers by recruiting the EZH2 containing repressive complex to the proximal RKIP promoter. Finally, we review the known mechanisms employed by different types of chemotherapeutic agents to activate RKIP expression in cancer cells.

  9. Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer.

    Science.gov (United States)

    Lorsy, Eva; Topuz, Aylin Sophie; Geisler, Cordelia; Stahl, Sarah; Garczyk, Stefan; von Stillfried, Saskia; Hoss, Mareike; Gluz, Oleg; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2016-01-01

    Dickkopf 3 (DKK3) has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791) we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS) of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype. PMID:27467270

  10. Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

    DEFF Research Database (Denmark)

    Hedegaard, Jakob; Lamy, Philippe; Nordentoft, Iver;

    2016-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like charac......Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal...... cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on...

  11. Early imaging findings in germ cell tumors arising from the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Mi [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Kyungpook National University Medical Center, Department of Radiology, Daegu (Korea, Republic of); Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cho, Hyun-Hae [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Ewha Woman' s University Mokdong Hospital, Department of Radiology, Seoul (Korea, Republic of); You, Sun Kyoung [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Chungnam National University Hospital, Department of Radiology, Daejeon (Korea, Republic of)

    2016-05-15

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  12. Signaling mechanisms and behavioral function of the mouse basal vomeronasal neuroepithelium.

    Science.gov (United States)

    Pérez-Gómez, Anabel; Stein, Benjamin; Leinders-Zufall, Trese; Chamero, Pablo

    2014-01-01

    The vomeronasal organ (VNO) is a sensory organ that is found in most terrestrial vertebrates and that is principally implicated in the detection of pheromones. The VNO contains specialized sensory neurons organized in a pseudostratified neuroepithelium that recognize chemical signals involved in initiating innate behavioral responses. In rodents, the VNO neuroepithelium is segregated into two distinct zones, apical and basal. The molecular mechanisms involved in ligand detection by apical and basal VNO sensory neurons differ extensively. These two VNO subsystems express different subfamilies of vomeronasal receptors and signaling molecules, detect distinct chemosignals, and project to separate regions of the accessory olfactory bulb (AOB). The roles that these olfactory subdivisions play in the control of specific olfactory-mediated behaviors are largely unclear. However, analysis of mutant mouse lines for signal transduction components together with identification of defined chemosensory ligands has revealed a fundamental role of the basal part of the mouse VNO in mediating a wide range of instinctive behaviors, such as aggression, predator avoidance, and sexual attraction. Here we will compare the divergent functions and synergies between the olfactory subsystems and consider new insights in how higher neural circuits are defined for the initiation of instinctive behaviors. PMID:25505388

  13. Signaling mechanisms and behavioral function of the mouse basal vomeronasal neuroepithelium

    Directory of Open Access Journals (Sweden)

    Anabel ePérez-Gómez

    2014-11-01

    Full Text Available The vomeronasal organ (VNO is a sensory organ that is found in most terrestrial vertebrates and that is principally implicated in the detection of pheromones. The VNO contains specialized sensory neurons organized in a pseudostratified neuroepithelium that recognize chemical signals involved in initiating innate behavioral responses. In rodents, the VNO neuroepithelium is segregated into two distinct zones, apical and basal. The molecular mechanisms involved in ligand detection by apical and basal VNO sensory neurons differ extensively. These two VNO subsystems express different subfamilies of vomeronasal receptors and signaling molecules, detect distinct chemosignals, and project to separate regions of the accessory olfactory bulb (AOB. The roles that these olfactory subdivisions play in the control of specific olfactory-mediated behaviors are largely unclear. However, analysis of mutant mouse lines for signal transduction components together with identification of defined chemosensory ligands has revealed a fundamental role of the basal part of the mouse VNO in mediating a wide range of instinctive behaviors, such as aggression, predator avoidance, and sexual attraction. Here we will compare the divergent functions and synergies between the olfactory subsystems and consider new insights in how higher neural circuits are defined for the initiation of instinctive behaviors.

  14. Early imaging findings in germ cell tumors arising from the basal ganglia

    International Nuclear Information System (INIS)

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  15. Transcription dynamics of inducible genes modulated by negative regulations.

    Science.gov (United States)

    Li, Yanyan; Tang, Moxun; Yu, Jianshe

    2015-06-01

    Gene transcription is a stochastic process in single cells, in which genes transit randomly between active and inactive states. Transcription of many inducible genes is also tightly regulated: It is often stimulated by extracellular signals, activated through signal transduction pathways and later repressed by negative regulations. In this work, we study the nonlinear dynamics of the mean transcription level of inducible genes modulated by the interplay of the intrinsic transcriptional randomness and the repression by negative regulations. In our model, we integrate negative regulations into gene activation process, and make the conventional assumption on the production and degradation of transcripts. We show that, whether or not the basal transcription is temporarily terminated when cells are stimulated, the mean transcription level grows in the typical up and down pattern commonly observed in immune response genes. With the help of numerical simulations, we clarify the delicate impact of the system parameters on the transcription dynamics, and demonstrate how our model generates the distinct temporal gene-induction patterns in mouse fibroblasts discerned in recent experiments.

  16. Factors related to RNA polymerase II transcription are localized in interchromatin granule clusters of Panorpa communis oocytes.

    Directory of Open Access Journals (Sweden)

    Vladimir Parfenov

    2009-05-01

    Full Text Available Diplotene oocyte nucleus of the scorpionfly Panorpa communis is transcriptionally silent and contains numerous nuclear bodies including interchromatin granule clusters (IGCs. The latter consist of the granules of 30-50 nm in diameter and contain IGC marker protein SC35 as well as RNA polymerase II. In this study, we also localized in P. communis oocyte IGCs the transcription coactivators CBP/p300, TATA-binding protein (TBP which is a component of the basal transcription factor TFIID and the basal transcription factor TFIIH. We belive that IGCs in transcriptionally inert P. communis oocytes are storage sites for the components of RNA polymerase II holoenzyme and other factors of RNA pol II transcription.

  17. Hydra constitutively expresses transcripts involved in vertebrate neural differentiation

    Indian Academy of Sciences (India)

    Sandipan Chatterjee; Shweta Lahudkar; N N Godbole; Surendra Ghaskadbi

    2001-06-01

    The diploblastic Hydra is among the most primitive multicellular organisms. Using cross-hybridization with Xenopus probes, noggin-like transcripts were detected in the hypostome and basal disc of adult Hydra (Pelmatohydra oligactis), regions with properties similar to that of the amphibian organizer. This points to the possibility of a close molecular similarity between the Xenopus and Hydra organizers. The constitutive expression of a noggin-like gene in Hydra may be responsible for its regenerative capacity.

  18. Rethinking transcription coupled DNA repair.

    Science.gov (United States)

    Kamarthapu, Venu; Nudler, Evgeny

    2015-04-01

    Nucleotide excision repair (NER) is an evolutionarily conserved, multistep process that can detect a wide variety of DNA lesions. Transcription coupled repair (TCR) is a subpathway of NER that repairs the transcribed DNA strand faster than the rest of the genome. RNA polymerase (RNAP) stalled at DNA lesions mediates the recruitment of NER enzymes to the damage site. In this review we focus on a newly identified bacterial TCR pathway in which the NER enzyme UvrD, in conjunction with NusA, plays a major role in initiating the repair process. We discuss the tradeoff between the new and conventional models of TCR, how and when each pathway operates to repair DNA damage, and the necessity of pervasive transcription in maintaining genome integrity. PMID:25596348

  19. Giant Basal Cell Carcinoma: A 12-Year Follow-up Case Report.

    Science.gov (United States)

    Jiménez-Hernández, Fabiola; Caballero-Centeno, Ana M; Barrera-Pérez, María; Ramos-Garibay, José A

    2016-01-01

    Giant basal cell carcinomas (GBCCs) are a strange and aggressive variety of basal cell carcinomas (BCCs); they are characterized by deep tissue invasion, rapid growth, high risk of metastasis, and a poor prognosis. GBCCs represent 0.4%-1% of all BCCs. The pathogenesis of GBCC is sometimes linked to a spontaneous mutation in the PTCH gene, mapped to the q22.33 locus of chromosome 9. The key factor in the development of GBCC, in at least 30% of the cases, is the delay in seeking medical attention (7.5 ± 3.1 years). This is associated to a poor socioeconomic level, deficient hygiene, mental illness, advanced age, and the fact that BCCs are painless lesions. The authors present a Mexican female with a 2-year ulcer diagnosed as a GBCC in the year 2000, its initial therapeutic approach, and her follow-up during the next 12 years. PMID:26332533

  20. Theoretical analysis of transcription process with polymerase stalling

    CERN Document Server

    Li, Jingwei

    2015-01-01

    Experimental evidences show that in gene transcription, RNA polymerase has the possibility to be stalled at certain position of the transcription template. This may be due to the template damage, or protein barriers. Once stalled, polymerase may backtrack along the template to the previous nucleotide to wait for the repair of the damaged site, or simply bypass the barrier or damaged site and consequently synthesize an incorrect messenger RNA, or degrade and detach from the template. Thus, the {\\it effective} transcription rate (the rate to synthesize correct product mRNA) and the transcription {\\it effectiveness} (the ratio of the {\\it effective} transcription rate to the {\\it effective} transcription initiation rate) are both influenced by polymerase stalling events. This study shows that, Without backtracking, detachment of stalled polymerase can also help to increase the {\\it effective} transcription rate and transcription {\\it effectiveness}. Generally, the increase of bypass rate of the stalled polymeras...

  1. [The Effect of Transcription on Enhancer Activity in Drosophila melanogaster].

    Science.gov (United States)

    Erokhin, M M; Davydova, A I; Lomaev, D V; Georgiev, P G; Chetverina, D A

    2016-01-01

    In higher eukaryotes, the level of gene transcription is under the control of DNA regulatory elements, such as promoter, from which transcription is initiated with the participation of RNA polymerase II and general transcription factors, as well as the enhancer, which increase the rate of transcription with the involvement of activator proteins and cofactors. It was demonstrated that enhancers are often located in the transcribed regions of the genome. We showed earlier that transcription negatively affected the activity of enhancers in Drosophila in model transgenic systems. In this study, we tested the effect of the distance between the leading promoter, enhancer, and target promoter on the inhibitory effect of transcriptions of different strengths. It was demonstrated that the negative effect of transcription remained, but weakened with increased distance between the leading promoter and enhancer and with decreased distance between the enhancer and target promoter. Thus, transcription can modulate the activity of enhancers by controlling its maximum level.

  2. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

    OpenAIRE

    Birgül Tepe

    2012-01-01

    Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic fac...

  3. Cortico-Basal Ganglia Circuit Function in Psychiatric Disease.

    Science.gov (United States)

    Gunaydin, Lisa A; Kreitzer, Anatol C

    2016-01-01

    Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico-basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders. PMID:26667072

  4. Dual transcriptional-translational cascade permits cellular level tuneable expression control.

    Science.gov (United States)

    Morra, Rosa; Shankar, Jayendra; Robinson, Christopher J; Halliwell, Samantha; Butler, Lisa; Upton, Mathew; Hay, Sam; Micklefield, Jason; Dixon, Neil

    2016-02-18

    The ability to induce gene expression in a small molecule dependent manner has led to many applications in target discovery, functional elucidation and bio-production. To date these applications have relied on a limited set of protein-based control mechanisms operating at the level of transcription initiation. The discovery, design and reengineering of riboswitches offer an alternative means by which to control gene expression. Here we report the development and characterization of a novel tunable recombinant expression system, termed RiboTite, which operates at both the transcriptional and translational level. Using standard inducible promoters and orthogonal riboswitches, a multi-layered modular genetic control circuit was developed to control the expression of both bacteriophage T7 RNA polymerase and recombinant gene(s) of interest. The system was benchmarked against a number of commonly used E. coli expression systems, and shows tight basal control, precise analogue tunability of gene expression at the cellular level, dose-dependent regulation of protein production rates over extended growth periods and enhanced cell viability. This novel system expands the number of E. coli expression systems for use in recombinant protein production and represents a major performance enhancement over and above the most widely used expression systems. PMID:26405200

  5. PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Jelena Marković

    Full Text Available Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12 transcription. The roles of poly(ADP-ribose polymerase-1 (PARP-1 and transcription factor Yin Yang 1 (YY1 in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the

  6. Ultrastructure of the basal lamina of bovine ovarian follicles and its relationship to the membrana granulosa.

    Science.gov (United States)

    Irving-Rodgers, H F; Rodgers, R J

    2000-03-01

    Different morphological phenotypes of follicular basal lamina and of membrana granulosa have been observed. Ten preantral follicles (basal lamina and membrana granulosa. Within each antral follicle, the shape of the basal cells of the membrana granulosa was uniform, and either rounded or columnar. There were equal proportions of follicles basal cells and with rounded basal cells. Larger follicles had only rounded basal cells. Conventional basal laminae of a single layer adjacent to the basal granulosa cells were observed in healthy follicles at the preantral and antral stages. However, at the preantral stage, the conventional types of basal lamina were enlarged or even partially laminated. A second type of basal lamina, described as 'loopy', occurred in about half the preantral follicles and in half the antral follicles basal laminae were not observed in larger follicles. 'Loopy' basal laminae were composed of basal laminae aligning the basal surface of basal granulosa cells, but with additional layers or loops often branching from the innermost layer. Each loop was usually Basal cellular processes were also common, and vesicles could be seen budding off from these processes. In antral follicles, conventional basal laminae occurred in follicles with rounded basal granulosa cells. Other follicles with columnar cells, and atretic follicles, had the 'loopy' basal lamina phenotype. Thus, follicles have different basal laminae that relate to the morphology of the membrana granulosa. PMID:10864785

  7. Influences of Plant Growth Regulators,Basal Media and Carbohydrate Levels on Cell Suspension Culture of Panax ginseng

    Institute of Scientific and Technical Information of China (English)

    TangWei; WuJiongyuan; 等

    1995-01-01

    A cell suspension culture of Panax ginseng which may be continuously subcultured has been established.Embryogenic callus derived from clutured young leaves was used to initiate the culture,Plant growth regulators,basal medium formula and carbohydrate levels were examined to determine their various effects on suspension culture cell growth and development ,The best selection of plant growth regulator,basal medium and carbohydrate level is 2mg/L 2,4-D:0.5mg/L KT,MS and 3% sucrose respectively.

  8. A 3' --> 5' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription.

    NARCIS (Netherlands)

    J.R. Hwang; V. Moncollin; W. Vermeulen (Wim); T. Seroz; H. van Vuuren; J.H.J. Hoeijmakers (Jan); J-M. Egly (Jean-Marc)

    1996-01-01

    textabstractXPB is a subunit of the basal transcription factor TFIIH, which is also involved in nucleotide excision repair (NER) and potentially in cell cycle regulation. A frameshift mutation in the 3'-end of the XPB gene is responsible for a concurrence of two disorders: xeroderma pigmentosum (XP)

  9. Morphology of nuclear transcription.

    Science.gov (United States)

    Weipoltshammer, Klara; Schöfer, Christian

    2016-04-01

    Gene expression control is a fundamental determinant of cellular life with transcription being the most important step. The spatial nuclear arrangement of the transcription process driven by RNA polymerases II and III is nonrandomly organized in foci, which is believed to add another regulatory layer on gene expression control. RNA polymerase I transcription takes place within a specialized organelle, the nucleolus. Transcription of ribosomal RNA directly responds to metabolic requirements, which in turn is reflected in the architecture of nucleoli. It differs from that of the other polymerases with respect to the gene template organization, transcription rate, and epigenetic expression control, whereas other features are shared like the formation of DNA loops bringing genes and components of the transcription machinery in close proximity. In recent years, significant advances have been made in the understanding of the structural prerequisites of nuclear transcription, of the arrangement in the nuclear volume, and of the dynamics of these entities. Here, we compare ribosomal RNA and mRNA transcription side by side and review the current understanding focusing on structural aspects of transcription foci, of their constituents, and of the dynamical behavior of these components with respect to foci formation, disassembly, and cell cycle. PMID:26847177

  10. A Nonnatural Transcriptional Coactivator

    Science.gov (United States)

    Nyanguile, Origene; Uesugi, Motonari; Austin, David J.; Verdine, Gregory L.

    1997-12-01

    In eukaryotes, sequence-specific DNA-binding proteins activate gene expression by recruiting the transcriptional apparatus and chromatin remodeling proteins to the promoter through protein-protein contacts. In many instances, the connection between DNA-binding proteins and the transcriptional apparatus is established through the intermediacy of adapter proteins known as coactivators. Here we describe synthetic molecules with low molecular weight that act as transcriptional coactivators. We demonstrate that a completely nonnatural activation domain in one such molecule is capable of stimulating transcription in vitro and in vivo. The present strategy provides a means of gaining external control over gene activation through intervention using small molecules.

  11. Basal ganglia calcification on computed tomography in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis. (author)

  12. [Extensive basal cell cancer of the scalp - case reports].

    Science.gov (United States)

    Olędzki, Szymon; Modrzejewski, Andrzej; Department Of Surgery And Emergency Nursing Pomeranian Medical University In Szczecin Poland, Ryszard

    2016-08-01

    Basal-cell canceris a slow growing, rarely metastasizes, locally malignant skin cancer. Patients with this neoplasm usually have excellent prognosis. Potentially, in some cases, a good prognosis cause a delay in therapy. Delay or withdrawal from treatment might lead to higher local extension of tumour with the destruction of the surrounding tissue. In this article we are presenting two patients with extensive basal cell cancer. The first patient underwent plastic surgery for extensive basal-cell carcinoma located in the parietal and temporal area. The second patient was observed due to recurrence of extensive basal cell carcinoma in the parietal region. Local advancement of the primary tumor could be a reason for the lack of radicality of surgery. Such advancement is rarely seen nowadays. The cases demonstrate the need for awareness about the possible severe course of the disease. PMID:27591446

  13. Basal ganglia calcification on computed tomography in systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki and others

    1988-09-01

    The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis.

  14. Short latency cerebellar modulation of the basal ganglia.

    Science.gov (United States)

    Chen, Christopher H; Fremont, Rachel; Arteaga-Bracho, Eduardo E; Khodakhah, Kamran

    2014-12-01

    The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  15. Basal cell carcinoma arising in a smallpox vaccination site.

    OpenAIRE

    Rich, J D; Shesol, B F; Horne, D W

    1980-01-01

    A case of pigmented basal cell carcinoma developing in a smallpox revaccination site is presented. Any progressive change within a smallpox vaccination scar should be thoroughly evaluated and treated appropriately after tissue diagnosis.

  16. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.

    Science.gov (United States)

    Torres, T; Fernandes, I; Costa, V; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  17. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma

    OpenAIRE

    Torres, T.; I. Fernandes; Costa, V.; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  18. Childhood trauma and basal cortisol in people with personality disorders

    OpenAIRE

    Flory, Janine D.; Yehuda, Rachel; Grossman, Robert; New, Antonia S.; Mitropoulou, Vivian; Siever, Larry J.

    2008-01-01

    This study examined the influence of various forms of childhood abuse on basal cortisol levels in a sample of adults with Axis II personality disorders. Participants included 63 adults (n=19 women) who provided basal plasma cortisol samples and completed the Childhood Trauma Questionnaire. Linear regression analyses that included all five subscales (i.e., sexual abuse, physical abuse, emotional abuse, physical neglect and emotional neglect) demonstrated that Physical abuse was related to lowe...

  19. Drosophila melanogaster as a model for basal body research

    OpenAIRE

    Jana, Swadhin Chandra; Bettencourt-Dias, Mónica; Durand, Bénédicte; Timothy L. Megraw

    2016-01-01

    The fruit fly, Drosophila melanogaster, is one of the most extensively studied organisms in biological research and has centrioles/basal bodies and cilia that can be modelled to investigate their functions in animals generally. Centrioles are nine-fold symmetrical microtubule-based cylindrical structures required to form centrosomes and also to nucleate the formation of cilia and flagella. When they function to template cilia, centrioles transition into basal bodies. The fruit fly has various...

  20. Nevoid basal cell carcinoma syndrome; Naevoid Basalzellkarzinom-Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Grgic, A.; Heinrich, M.; Heckmann, M.; Kramann, B. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Aliani, S. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Klinik fuer Kinder- und Jugendmedizin; Dill-Mueller, D. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Hautklinik und Poliklinik; Uder, M. [Erlange-Nuernberg Univ. (Germany). Inst. fuer Diagnostische Radiologie

    2005-07-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. The combination of clinical, imaging, and histological findings is helpful in identifying NBCCS patients. Imaging plays a crucial role in evaluation of these patients. We present a wide variety of clinical and radiological findings characteristic of this disease. (orig.)

  1. [Basal cell carcinoma. Molecular genetics and unusual clinical features].

    Science.gov (United States)

    Reifenberger, J

    2007-05-01

    Basal cell carcinoma is the most common human cancer. Its incidence is steadily increasing. The development of basal cell carcinoma is linked to genetic factors, including the individual skin phototype, as well as the cumulative exposure to UVB. The vast majority of basal cell carcinomas are sporadic tumors, while familial cases associated with certain hereditary syndromes are less common. At the molecular level, basal cell carcinomas are characterized by aberrant activation of sonic hedgehog signaling, usually due to mutations either in the ptch or smoh genes. In addition, about half of the cases carry mutations in the tp53 tumor suppressor gene, which are often UVB-associated C-->T transition mutations. Clinically, basal cell carcinomas may show a high degree of phenotypical variability. In particular, tumors occurring in atypical locations, showing an unusual clinical appearance, or imitating other skin diseases may cause diagnostic problems. This review article summarizes the current state of the art concerning the etiology, predisposition and molecular genetics of basal cell carcinoma. In addition, examples of unusual clinical manifestations are illustrated. PMID:17440702

  2. Laser ablation of basal cell carcinomas guided by confocal microscopy

    Science.gov (United States)

    Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

    2016-02-01

    Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

  3. Endogenous synchronous fluorescence spectroscopy (SFS) of basal cell carcinoma-initial study

    Science.gov (United States)

    Borisova, E.; Zhelyazkova, Al.; Keremedchiev, M.; Penkov, N.; Semyachkina-Glushkovskaya, O.; Avramov, L.

    2016-01-01

    The human skin is a complex, multilayered and inhomogeneous organ with spatially varying optical properties. Analysis of cutaneous fluorescence spectra could be a very complicated task; therefore researchers apply complex mathematical tools for data evaluation, or try to find some specific approaches, that would simplify the spectral analysis. Synchronous fluorescence spectroscopy (SFS) allows improving the spectral resolution, which could be useful for the biological tissue fluorescence characterization and could increase the tumour detection diagnostic accuracy.

  4. Transcription factors as targets of anticancer drugs.

    Science.gov (United States)

    Gniazdowski, M; Czyz, M

    1999-01-01

    Several general and gene- and cell-selective transcription factors are required for specific transcription to occur. Many of them exert their functions through specific contacts either in the promoter region or at distant sequences regulating the initiation. These contacts may be altered by anticancer drugs which form non-covalent complexes with DNA. Covalent modifications of DNA by alkylating agents may prevent transcription factors from recognizing their specific sequences or may constitute multiple "unnatural" binding sites in DNA which attract the factors thus decreasing their availability in the cell. The anticancer drug-transcription factor interplay which is based on specific interactions with DNA may contribute to pharmacological properties of the former and provide a basis for the search for new drugs. PMID:10547027

  5. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters

    Science.gov (United States)

    Lavender, Christopher A.; Hoffman, Jackson A.; Trotter, Kevin W.; Gilchrist, Daniel A.; Bennett, Brian D.; Burkholder, Adam B.; Fargo, David C.; Archer, Trevor K.

    2016-01-01

    Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment. PMID:27487356

  6. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.

    Science.gov (United States)

    Lavender, Christopher A; Cannady, Kimberly R; Hoffman, Jackson A; Trotter, Kevin W; Gilchrist, Daniel A; Bennett, Brian D; Burkholder, Adam B; Burd, Craig J; Fargo, David C; Archer, Trevor K

    2016-08-01

    Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment. PMID:27487356

  7. Axillary basal cell carcinoma in patients with Goltz-Gorlin syndrome: report of basal cell carcinoma in both axilla of a woman with basal cell nevus syndrome and literature review

    OpenAIRE

    Cohen, Philip R.

    2014-01-01

    Background: Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas.Purpose: To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome.Methods: Pubmed w...

  8. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein codi...

  9. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I;

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  10. Biophysical models of transcription in cells

    Science.gov (United States)

    Choubey, Sandeep

    Cells constantly face environmental challenges and deal with them by changing their gene expression patterns. They make decisions regarding which genes to express and which genes not to express based on intra-cellular and environmental cues. These decisions are often made by regulating the process of transcription. While the identities of the different molecules that take part in regulating transcription have been determined for a number of different genes, their dynamics inside the cell are still poorly understood. One key feature of these regulatory dynamics is that the numbers of the bio-molecules involved is typically small, resulting in large temporal fluctuations in transcriptional outputs (mRNA and protein). In this thesis I show that measurements of the cell-to-cell variability of the distribution of transcribing RNA polymerases along a gene provide a previously unexplored method for deciphering the mechanism of its transcription in vivo. First, I propose a simple kinetic model of transcription initiation and elongation from which I calculate transcribing RNA polymerase copy-number fluctuations. I test my theory against published data obtained for yeast genes and propose a novel mechanism of transcription. Rather than transcription being initiated through a single rate-limiting step, as was previously proposed, my single-cell analysis reveals the presence of at least two rate limiting steps. Second, I compute the distribution of inter-polymerase distance distribution along a gene and propose a method for analyzing inter-polymerase distance distributions acquired in experiments. By applying this method to images of polymerases transcribing ribosomal genes in E.coli I show that one model of regulation of these genes is consistent with inter-polymerase distance data while a number of other models are not. The analytical framework described in this thesis can be used to extract quantitative information about the dynamics of transcription from single

  11. The synapsin gene family in basal chordates: evolutionary perspectives in metazoans

    Directory of Open Access Journals (Sweden)

    De Bernardi Fiorenza

    2010-01-01

    Full Text Available Abstract Background Synapsins are neuronal phosphoproteins involved in several functions correlated with both neurotransmitter release and synaptogenesis. The comprehension of the basal role of the synapsin family is hampered in vertebrates by the existence of multiple synapsin genes. Therefore, studying homologous genes in basal chordates, devoid of genome duplication, could help to achieve a better understanding of the complex functions of these proteins. Results In this study we report the cloning and characterization of the Ciona intestinalis and amphioxus Branchiostoma floridae synapsin transcripts and the definition of their gene structure using available C. intestinalis and B. floridae genomic sequences. We demonstrate the occurrence, in both model organisms, of a single member of the synapsin gene family. Full-length synapsin genes were identified in the recently sequenced genomes of phylogenetically diverse metazoans. Comparative genome analysis reveals extensive conservation of the SYN locus in several metazoans. Moreover, developmental expression studies underline that synapsin is a neuronal-specific marker in basal chordates and is expressed in several cell types of PNS and in many, if not all, CNS neurons. Conclusion Our study demonstrates that synapsin genes are metazoan genes present in a single copy per genome, except for vertebrates. Moreover, we hypothesize that, during the evolution of synapsin proteins, new domains are added at different stages probably to cope up with the increased complexity in the nervous system organization. Finally, we demonstrate that protochordate synapsin is restricted to the post-mitotic phase of CNS development and thereby is a good marker of postmitotic neurons.

  12. A case of multiple basal cell carcinomas developed about 50 years after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Chu; Minamimoto, Toshiyuki; Hamada, Yoshimi; Sasaki, Harue; Furuya, Kazuhiko [Hakodate Central General Hospital, Hokkaido (Japan); Funayama, Emi

    1998-10-01

    Malignant skin tumors are known to develop in areas of chronic radiodermatitis. We experienced a patient with multiple basal cell carcinomas that developed about 50 years after irradiation. The patient was a 77-year-old man who underwent radiotherapy in his twenties for caries in the left shoulder joint. The dose given was unknown. Black skin tumor appeared initially about 10 years before the first consultation. The skin around the tumor began to erode about six months before presentation. Biopsy of the tumor was done at another institution and revealed basal cell carcinoma (BCC), so the patients was referred to our department. In addition to the BCC measuring 35 x 20 mm in the left shoulder, BCC measuring 17 x 20 mm and 15 x 15 mm were found on the chest and the left axilla, respectively. The lesions were excised with a margin of 5 mm from the radiodermatitis, and the resultant skin defects were covered with latissimus dorsi flaps. All three tumors were basal cell carcinomas. The patients died of an unrelated disease six years after surgery and there was no recurrence of his tumors. (author)

  13. Floral gene resources from basal angiosperms for comparative genomics research

    Directory of Open Access Journals (Sweden)

    Zhang Xiaohong

    2005-03-01

    Full Text Available Abstract Background The Floral Genome Project was initiated to bridge the genomic gap between the most broadly studied plant model systems. Arabidopsis and rice, although now completely sequenced and under intensive comparative genomic investigation, are separated by at least 125 million years of evolutionary time, and cannot in isolation provide a comprehensive perspective on structural and functional aspects of flowering plant genome dynamics. Here we discuss new genomic resources available to the scientific community, comprising cDNA libraries and Expressed Sequence Tag (EST sequences for a suite of phylogenetically basal angiosperms specifically selected to bridge the evolutionary gaps between model plants and provide insights into gene content and genome structure in the earliest flowering plants. Results Random sequencing of cDNAs from representatives of phylogenetically important eudicot, non-grass monocot, and gymnosperm lineages has so far (as of 12/1/04 generated 70,514 ESTs and 48,170 assembled unigenes. Efficient sorting of EST sequences into putative gene families based on whole Arabidopsis/rice proteome comparison has permitted ready identification of cDNA clones for finished sequencing. Preliminarily, (i proportions of functional categories among sequenced floral genes seem representative of the entire Arabidopsis transcriptome, (ii many known floral gene homologues have been captured, and (iii phylogenetic analyses of ESTs are providing new insights into the process of gene family evolution in relation to the origin and diversification of the angiosperms. Conclusion Initial comparisons illustrate the utility of the EST data sets toward discovery of the basic floral transcriptome. These first findings also afford the opportunity to address a number of conspicuous evolutionary genomic questions, including reproductive organ transcriptome overlap between angiosperms and gymnosperms, genome-wide duplication history, lineage

  14. Basal-topographic control of stationary ponds on a continuously moving landslide

    Science.gov (United States)

    Coe, J.A.; McKenna, J.P.; Godt, J.W.; Baum, R.L.

    2009-01-01

    analyses of translational landslides should attempt to incorporate irregular basal surface topography. Additional implications for moving landslides where basal topography controls surface morphology include the following: dateable sediments or organic material from basal layers of stationary ponds will yield ages that are younger than the date of landslide initiation, and it is probable that other landslide surface features such as faults, streams, springs and sinks are also controlled by basal topography. The longitudinal topographic profile indicated that the upper part of the Slumgullion landslide was depleted at a mean vertical lowering rate of 5.6 cm/yr between 1939 and 2000, while the toe advanced at an average rate of 1.5 m/yr during the same period. Therefore, during this 61-year period, neither the depletion of material at the head of the landslide nor continued growth of the landslide toe has decreased the overall movement rate of the landslide. Continued depletion of the upper part of the landslide, and growth of the toe, should eventually result in stabilization of the landslide. Copyright ?? 2008 John Wiley & Sons, Ltd.

  15. Nanoelectroablation therapy for murine basal cell carcinoma

    International Nuclear Information System (INIS)

    Highlights: ► Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. ► Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. ► Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. ► Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1+/−K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5–7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 ± 5 (SEM) mm3 shrunk by 76 ± 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  16. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  17. Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex.

    Directory of Open Access Journals (Sweden)

    Fong Kuan Wong

    2015-08-01

    Full Text Available The evolutionary expansion of the neocortex in mammals has been linked to enlargement of the subventricular zone (SVZ and increased proliferative capacity of basal progenitors (BPs, notably basal radial glia (bRG. The transcription factor Pax6 is known to be highly expressed in primate, but not mouse, BPs. Here, we demonstrate that sustaining Pax6 expression selectively in BP-genic apical radial glia (aRG and their BP progeny of embryonic mouse neocortex suffices to induce primate-like progenitor behaviour. Specifically, we conditionally expressed Pax6 by in utero electroporation using a novel, Tis21-CreERT2 mouse line. This expression altered aRG cleavage plane orientation to promote bRG generation, increased cell-cycle re-entry of BPs, and ultimately increased upper-layer neuron production. Upper-layer neuron production was also increased in double-transgenic mouse embryos with sustained Pax6 expression in the neurogenic lineage. Strikingly, increased BPs existed not only in the SVZ but also in the intermediate zone of the neocortex of these double-transgenic mouse embryos. In mutant mouse embryos lacking functional Pax6, the proportion of bRG among BPs was reduced. Our data identify specific Pax6 effects in BPs and imply that sustaining this Pax6 function in BPs could be a key aspect of SVZ enlargement and, consequently, the evolutionary expansion of the neocortex.

  18. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    徐进平; 叶林柏

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  19. Transcription regulatory elements are punctuation marks for DNA replication.

    Science.gov (United States)

    Mirkin, Ekaterina V; Castro Roa, Daniel; Nudler, Evgeny; Mirkin, Sergei M

    2006-05-01

    Collisions between DNA replication and transcription significantly affect genome organization, regulation, and stability. Previous studies have described collisions between replication forks and elongating RNA polymerases. Although replication collisions with the transcription-initiation or -termination complexes are potentially even more important because most genes are not actively transcribed during DNA replication, their existence and mechanisms remained unproven. To address this matter, we have designed a bacterial promoter that binds RNA polymerase and maintains it in the initiating mode by precluding the transition into the elongation mode. By using electrophoretic analysis of replication intermediates, we have found that this steadfast transcription-initiation complex inhibits replication fork progression in an orientation-dependent manner during head-on collisions. Transcription terminators also appeared to attenuate DNA replication, but in the opposite, codirectional orientation. Thus, transcription regulatory signals may serve as "punctuation marks" for DNA replication in vivo. PMID:16670199

  20. Systematic clustering of transcription start site landscapes

    DEFF Research Database (Denmark)

    Zhao, Xiaobei; Valen, Eivind; Parker, Brian J;

    2011-01-01

    Genome-wide, high-throughput methods for transcription start site (TSS) detection have shown that most promoters have an array of neighboring TSSs where some are used more than others, forming a distribution of initiation propensities. TSS distributions (TSSDs) vary widely between promoters...

  1. How do our prior assumptions about basal drag affect ice sheet forecasts?

    Science.gov (United States)

    Arthern, Robert

    2015-04-01

    Forecasts of changes in the large ice sheets of Greenland and Antarctica often begin with an inversion to select initial values for state variables and parameters in the model, such as basal drag and ice viscosity. These inversions can be ill-posed in the sense that many different choices for the parameter values can match the observational data equally well. To recover a mathematically well-posed problem, assumptions must be made that restrict the possible values of the parameters, either by regularisation or by explicit definition of Bayesian priors. Common assumptions are that parameters vary smoothly in space or lie close to some preferred initial guess, but for glaciological inversions it is often unclear how smoothly the parameters should vary, or how reliable the initial guess should be considered. This is especially true of inversions for the basal drag coefficient that can vary enormously from place to place on length scales set by subglacial hydrology, which is itself extremely poorly constrained by direct observations. Here we use a combination of forward modelling, inversion and a theoretical analysis based on transformation group priors to investigate different ways of introducing prior information about parameters, and to consider the consequences for ice sheet forecasts.

  2. Serial dynamic CT scan in patients with acute basal ganglia infarctions

    International Nuclear Information System (INIS)

    Dynamic computed tomography (CT) was performed on 15 patients (37 to 93 years of age) with acute basal ganglia infarctions, and the perfusion patterns of the infarcted regions on CT were evaluated. The initial dynamic CT was performed within 12 hours after onset, while the serial studies of the dynamic CT were performed on the 3rd and 7th days. The left-over-right ratio in the peak value in the basal ganglia in 15 normal subjects was 1.01 ± 0.03 (mean ± SD), so there were no differences in the peak values of the bilateral basal ganglia. We also examined the left-over-right ratio in the peak value and in the rapid-washout ratio in the basal ganglia in the 15 normal subjects. There was no difference in the peak values of the bilateral basal ganglia. The mean rapid-washout ratio was 0.62 ± 0.11 (mean ± SD). The prognoses of these patients three months after onset were as follows: 8 showed a good recovery, 5 had a moderate disability, and 2 had a severe disability. The perfusions on admission were as follows. 10 were hypoperfusions, 3 were hypo + late perfusions, one was a normoperfusion, and one was a late perfusion. There was a tendency for the rapid-washout ratio decrease more in the hypo + late perfusion group than in the other groups. Twelve patients showed an iso-density, while 3 showed a low density, on admission. The ''low-density'' group showed a decrease in the A/N ratio of the peak value. We performed serial dynamic CT in 11 cases. The group with severe disabilities (2 cases) showed a hypo + late perfusion in the initial CT, one case kept a hypo + late perfusion, and another case changed to a hypoperfusion; also, there was a tendency for there to be a poor improvement in the A/N ratio of the peak value in these two ''severe-disability'' patients. (J.P.N.)

  3. Dopamine-glutamate interactions in the basal ganglia.

    Science.gov (United States)

    Schmidt, W J

    1998-01-01

    In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of "wanted" and in the suppression of "unwanted" behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar functions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia functions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801. PMID:9871434

  4. Nuclear stability and transcriptional directionality separate functionally distinct RNA species

    DEFF Research Database (Denmark)

    Andersson, Robin; Refsing Andersen, Peter; Valen, Eivind;

    2014-01-01

    by their sensitivity to the ribonucleolytic RNA exosome complex and by the nature of their transcription initiation. These measures are surprisingly effective at correctly classifying annotated transcripts, including lncRNAs of known function. The approach also identifies uncharacterized stable lncRNAs, hidden among...

  5. Divergent RNA transcription: a role in promoter unwinding?

    Science.gov (United States)

    Naughton, Catherine; Corless, Samuel; Gilbert, Nick

    2013-01-01

    New approaches using biotinylated-psoralen as a probe for investigating DNA structure have revealed new insights into the relationship between DNA supercoiling, transcription and chromatin compaction. We explore a hypothesis that divergent RNA transcription generates negative supercoiling at promoters facilitating initiation complex formation and subsequent promoter clearance.

  6. Synchronizing activity of basal ganglia and pathophysiology of Parkinson's disease.

    Science.gov (United States)

    Heimer, G; Rivlin, M; Israel, Z; Bergman, H

    2006-01-01

    Early physiological studies emphasized changes in the discharge rate of basal ganglia in the pathophysiology of Parkinson's disease (PD), whereas recent studies stressed the role of the abnormal oscillatory activity and neuronal synchronization of pallidal cells. However, human observations cast doubt on the synchronization hypothesis since increased synchronization may be an epi-phenomenon of the tremor or of independent oscillators with similar frequency. Here, we show that modern actor/ critic models of the basal ganglia predict the emergence of synchronized activity in PD and that significant non-oscillatory and oscillatory correlations are found in MPTP primates. We conclude that the normal fluctuation of basal ganglia dopamine levels combined with local cortico-striatal learning rules lead to noncorrelated activity in the pallidum. Dopamine depletion, as in PD, results in correlated pallidal activity, and reduced information capacity. We therefore suggest that future deep brain stimulation (DBS) algorithms may be improved by desynchronizing pallidal activity. PMID:17017503

  7. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Birgül Tepe

    2012-06-01

    Full Text Available Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic factor except for chronic sunlight exposure. The aim of our report is to show that this prevalant cutaneous malignancy can be encountered in rare/unusual areas. (Turk J Dermatol 2012; 6: 51-4

  8. The Transcription Bubble of the RNA Polymerase-Promoter Open Complex Exhibits Conformational Heterogeneity and Millisecond-Scale Dynamics : Implications for Transcription Start-Site Selection

    NARCIS (Netherlands)

    Robb, Nicole C.; Cordes, Thorben; Hwang, Ling Chin; Gryte, Kristofer; Duchi, Diego; Craggs, Timothy D.; Santoso, Yusdi; Weiss, Shimon; Ebright, Richard H.; Kapanidis, Achillefs N.

    2013-01-01

    Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts similar to 14 bp around the transcription start site and forms a single-stranded "transcription bubble" within a catalytically active RNAP-DNA open complex (RPo). There is significant flexibility in the tra

  9. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Directory of Open Access Journals (Sweden)

    Milka Martinez

    Full Text Available RUNX1 a member of the family of runt related transcription factors (RUNX, is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  10. A review of stand basal area growth models

    Institute of Scientific and Technical Information of China (English)

    Sun Hong-gang; Zhang Jian-guo; Duan Ai-guo; He Cai-yun

    2007-01-01

    Growth and yield modeling has a long history in forestry. The methods of measuring the growth of stand basal area have evolved from those developed in the U.S.A. and Germany during the last century. Stand basal area modeling has progressed rapidly since the first widely used model was published by the U.S. Forest Service. Over the years, a variety of models have been developed for predicting the growth and yield of uneven/even-aged stands using stand-level approaches. The modeling methodology has not only moved from an empirical approach to a more ecological process-based approach but also accommodated a variety of techniques such as: 1) simultaneous equation methods, 2) difference models, 3) artificial neural network techniques, 4) linear/nonlinear regression models, and 5) matrix models. Empirical models using statistical methods were developed to reproduce accurately and precisely field observations. In contrast, process models have a shorter history, developed originally as research and education tools with the aim of increasing the understanding of cause and effect relationships. Empirical and process models can be married into hybrid models in which the shortcomings of both component approaches can, to some extent, be overcome. Algebraic difference forms of stand basal area models which consist of stand age, stand density and site quality can fully describe stand growth dynamics. This paper reviews the current literature regarding stand basal area models, discusses the basic types of models and their merits and outlines recent progress in modeling growth and dynamics of stand basal area. Future trends involving algebraic difference forms, good fitting variables and model types into stand basal area modeling strategies are discussed.

  11. Kinome expression profiling and prognosis of basal breast cancers

    Directory of Open Access Journals (Sweden)

    Jacquemier Jocelyne

    2011-07-01

    Full Text Available Abstract Background Basal breast cancers (BCs represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES. Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling. Methods DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set. Results A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73. This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518 sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test. Conclusions Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.

  12. The {Delta}Np63 Proteins Are Key Allies of BRCA1 in the Prevention of Basal-Like Breast Cancer.

    LENUS (Irish Health Repository)

    Buckley, Niamh E

    2011-03-01

    Little is known about the origin of basal-like breast cancers, an aggressive disease that is highly similar to BRCA1-mutant breast cancers. p63 family proteins that are structurally related to the p53 suppressor protein are known to function in stem cell regulation and stratified epithelia development in multiple tissues, and p63 expression may be a marker of basal-like breast cancers. Here we report that ΔNp63 isoforms of p63 are transcriptional targets for positive regulation by BRCA1. Our analyses of breast cancer tissue microarrays and BRCA1-modulated breast cancer cell lines do not support earlier reports that p63 is a marker of basal-like or BRCA1 mutant cancers. Nevertheless, we found that BRCA1 interacts with the specific p63 isoform ΔNp63γ along with transcription factor isoforms AP-2α and AP-2γ. BRCA1 required ΔNp63γ and AP-2γ to localize to an intronic enhancer region within the p63 gene to upregulate transcription of the ΔNp63 isoforms. In mammary stem\\/progenitor cells, siRNA-mediated knockdown of ΔNp63 expression resulted in genomic instability, increased cell proliferation, loss of DNA damage checkpoint control, and impaired growth control. Together, our findings establish that transcriptional upregulation of ΔNp63 proteins is critical for BRCA1 suppressor function and that defects in BRCA1-ΔNp63 signaling are key events in the pathogenesis of basal-like breast cancer. Cancer Res; 71(5); 1933-44. ©2011 AACR.

  13. Prevention of KLF4-mediated tumor initiation and malignant transformation by UAB30 rexinoid.

    Science.gov (United States)

    Jiang, Wen; Deng, Wentao; Bailey, Sarah K; Nail, Clint D; Frost, Andra R; Brouillette, Wayne J; Muccio, Donald D; Grubbs, Clinton J; Ruppert, J Michael; Lobo-Ruppert, Susan M

    2009-02-01

    The transcription factor KLF4 acts in post-mitotic epithelial cells to promote differentiation and functions in a context-dependent fashion as an oncogene. In the skin KLF4 is co-expressed with the nuclear receptors RARgamma and RXRalpha, and formation of the skin permeability barrier is a shared function of these three proteins. We utilized a KLF4-transgenic mouse model of skin cancer in combination with cultured epithelial cells to examine functional interactions between KLF4 and retinoic acid receptors. In cultured cells, activation of a conditional, KLF4-estrogen receptor fusion protein by 4-hydroxytamoxifen resulted in rapid upregulation of transcripts for nuclear receptors including RARgamma and RXRalpha. We tested retinoids in epithelial cell transformation assays, including an RAR-selective agonist (all-trans RA), an RXR-selective agonist (9-cis UAB30, rexinoid), and a pan agonist (9-cis RA). Unlike for several other genes, transformation by KLF4 was inhibited by each retinoid, implicating distinct nuclear receptor heterodimers as modulators of KLF4 transforming activity. When RXRalpha expression was suppressed by RNAi in cultured cells, transformation was promoted and the inhibitory effect of 9-cis UAB30 was attenuated. Similarly as shown for other mouse models of skin cancer, rexinoid prevented skin tumor initiation resulting from induction of KLF4 in basal keratinocytes. Rexinoid permitted KLF4 expression and KLF4-induced cell cycling, but attenuated the KLF4-induced misexpression of cytokeratin 1 in basal cells. Neoplastic lesions including hyperplasia, dysplasia and squamous cell carcinoma-like lesions were prevented for up to 30 days. Taken together, the results identify retinoid receptors including RXRalpha as ligand-dependent inhibitors of KLF4-mediated transformation or tumorigenesis. PMID:19197145

  14. Basal conditions and ice dynamics inferred from radar-derived internal stratigraphy of the Northeast Greenland Ice Stream

    Science.gov (United States)

    Keisling, B. A.; Christianson, K. A.; Alley, R. B.; Peters, L. E.; Christian, J. E.; Anandakrishnan, S.; Riverman, K. L.; Muto, A.; Jacobel, R. W.

    2013-12-01

    We present radio-echo sounding (RES), global positioning system (GPS) and active source seismic data from the central portion of the Northeast Greenland Ice Stream ~150 km downstream from the onset of streaming flow, which likely initiates due to locally high geothermal flux (~1 W/m2) near the ice sheet summit. Our geophysical data show that ice stream extent is limited via a feedback between basal hydrology and ice sheet surface elevation change. Active-source seismic data reveal water-saturated till beneath the central trunk of streaming flow. Subglacial till becomes increasingly dewatered and consolidated toward the shear margins. We hypothesize that ice accelerates and thins as it flows into NEGIS, producing marginal troughs in surface topography. These troughs create steep gradients in the subglacial hydropotential that generate parallel slippery and sticky bands beneath the margins, which limit ice entrainment across the margin and thus restrict further widening. Complex steady-state folds in radar reflectors within the shear margins form due to the combined influence of geothermal flux, varying basal shear stress, flow convergence, and bands of variable basal friction. Our strain rate and flux analysis of radar internal layers indicates no major changes in flow dynamics during the past ~10,000 years. However, strain rate modeling suggests that steady-state basal shear heating produces plentiful meltwater beneath the central trunk of streaming flow in addition to that supplied by geothermal flux. This meltwater supports the basal lubrication necessary to maintain streaming flow and may allow remobilization of dewatered marginal till. While the main trunk of streaming flow is remarkably stable, complex processes occurring within the shear margins merit closer scrutiny. The feedback between surface elevation change and basal water routing could mobilize currently unconsolidated sediments in the margins and result in shifts in ice dynamics.

  15. Dietary Conjugated Linoleic Acid Supplementation Leads to Downregulation of PPAR Transcription in Broiler Chickens and Reduction of Adipocyte Cellularity

    OpenAIRE

    Suriya Kumari Ramiah; Goh Yong Meng; Tan Sheau Wei; Yeap Swee Keong; Mahdi Ebrahimi

    2014-01-01

    Conjugated linoleic acids (CLA) act as an important ligand for nuclear receptors in adipogenesis and fat deposition in mammals and avian species. This study aimed to determine whether similar effects are plausible on avian abdominal fat adipocyte size, as well as abdominal adipogenic transcriptional level. CLA was supplemented at different levels, namely, (i) basal diet without CLA (5% palm oil) (CON), (ii) basal diet with 2.5% CLA and 2.5% palm oil (LCLA), and (iii) basal diet with 5% CLA (H...

  16. Myogenesis in the basal bilaterian Symsagittifera roscoffensis (Acoela

    Directory of Open Access Journals (Sweden)

    Wanninger Andreas

    2008-09-01

    Full Text Available Abstract Background In order to increase the weak database concerning the organogenesis of Acoela – a clade regarded by many as the earliest extant offshoot of Bilateria and thus of particular interest for studies concerning the evolution of animal bodyplans – we analyzed the development of the musculature of Symsagittifera roscoffensis using F-actin labelling, confocal laserscanning microscopy, and 3D reconstruction software. Results At 40% of development between egg deposition and hatching short subepidermal fibres form. Muscle fibre development in the anterior body half precedes myogenesis in the posterior half. At 42% of development a grid of outer circular and inner longitudinal muscles is present in the bodywall. New circular muscles either branch off from present fibres or form adjacent to existing ones. The number of circular muscles is higher than that of the longitudinal muscles throughout all life cycle stages. Diagonal, circular and longitudinal muscles are initially rare but their number increases with time. The ventral side bears U-shaped muscles around the mouth, which in addition is surrounded by a sphincter muscle. With the exception of the region of the statocyst, dorsoventral muscles are present along the entire body of juveniles and adults, while adults additionally exhibit radially oriented internal muscles in the anterior tip. Outer diagonal muscles are present at the dorsal anterior tip of the adult. In adult animals, the male gonopore with its associated sexual organs expresses distinct muscles. No specific statocyst muscles were found. The muscle mantles of the needle-shaped sagittocysts are situated along the lateral edges of the animal and in the posterior end close to the male gonopore. In both juveniles and adults, non-muscular filaments, which stain positively for F-actin, are associated with certain sensory cells outside the bodywall musculature. Conclusion Compared to the myoanatomy of other acoel taxa

  17. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  18. Post-Transcriptional Mechanisms Regulating Epidermal Stem and Progenitor Cell Self-Renewal and Differentiation.

    Science.gov (United States)

    Li, Jingting; Sen, George L

    2016-04-01

    Epidermal stem and progenitor cells exist within the basal layer of the epidermis and serve to replenish the loss of differentiated cells because of normal turnover or injury. Current efforts have focused on elucidating the transcriptional regulation of epidermal stem cell self-renewal and differentiation. However, recent studies have pointed to an emerging and prominent role for post-transcriptional regulation of epidermal cell fate decisions. In this review, we will focus on post-transcriptional mechanisms including noncoding RNAs, RNA binding proteins, and mRNA decay-mediated control of epidermal stem and progenitor cell function in the skin.

  19. Transcription reactions of yeast RNA polymerase II in vitro

    Institute of Scientific and Technical Information of China (English)

    赵宇; 敖世洲

    1995-01-01

    The transcription reactions in vitro of yeast ADHl and PHO5 gene promoters are investigated by means of a yeast crude nuclear extract. Using specific RNA probes, the transcription products of these 2 promoters have been first obtained. A low concentration of α-amanitin is highly inhibitory. The transcription of the PHO5 gene was initiated in vitro at or near the sites used in vim. The transcription products increase with the amount of the template and reach the maximum at certain concentrations of the template. The deletion of the yeast promoter sequences abolishes the reaction.

  20. Distinct regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID.

    Science.gov (United States)

    Bhaumik, Sukesh R

    2011-02-01

    A growing number of human diseases are linked to abnormal gene expression which is largely controlled at the level of transcriptional initiation. The gene-specific activator promotes the initiation of transcription through its interaction with one or more components of the transcriptional initiation machinery, hence leading to stimulated transcriptional initiation or activation. However, all activator proteins do not target the same component(s) of the transcriptional initiation machinery. Rather, they can have different target specificities, and thus, can lead to distinct mechanisms of transcriptional activation. Two such distinct mechanisms of transcriptional activation in yeast are mediated by the SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (Transcription factor IID) complexes, and are termed as "SAGA-dependent" and "TFIID-dependent" transcriptional activation, respectively. SAGA is the target of the activator in case of SAGA-dependent transcriptional activation, while the targeting of TFIID by the activator leads to TFIID-dependent transcriptional activation. Both the SAGA and TFIID complexes are highly conserved from yeast to human, and play crucial roles in gene activation among eukaryotes. The regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID are discussed here. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!

  1. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    Faria, J.

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  2. Pigmented Basal Cell Carcinoma: A Clinical Variant, Report of Two Cases

    OpenAIRE

    K., Deepadarshan; M., Mallikarjun; N. Abdu, Noshin

    2013-01-01

    Basal cell carcinoma is the most common malignant tumour of skin, comprising 80% of non-melanoma cancers. Intermittent exposure to ultraviolet radiation is an important risk factor. Pigmented basal cell carcinoma is a clinical and histological variant of basal cell carcinoma that exhibits increased pigmentation. It is a very rare variant, although its frequency can reach upto 6% of total basal cell carcinomas in Hispanics. Herein, we are reporting 2 cases of pigmented basal cell carcinoma.

  3. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage.

    Directory of Open Access Journals (Sweden)

    Nisha M Badders

    Full Text Available BACKGROUND: Ectopic Wnt signaling induces increased stem/progenitor cell activity in the mouse mammary gland, followed by tumor development. The Wnt signaling receptors, Lrp5/6, are uniquely required for canonical Wnt activity. Previous data has shown that the absence of Lrp5 confers resistance to Wnt1-induced tumor development. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion. Though Wnt dependent transcription of key target genes is relatively unchanged in mammary epithelial cell cultures, the absence of Lrp5 specifically depletes adult regenerative stem cell activity (to less than 1%. Stem cell activity can be enriched by >200 fold (over 80% of activity, based on high Lrp5 expression alone. Though Lrp5 null glands have apparent normal function, the basal lineage is relatively reduced (from 42% basal/total epithelial cells to 22% and Lrp5-/- mammary epithelial cells show enhanced expression of senescence-associated markers in vitro, as measured by expression of p16(Ink4a and TA-p63. CONCLUSIONS/SIGNIFICANCE: This is the first single biomarker that has been demonstrated to be functionally involved in stem cell maintenance. Together, these results demonstrate that Wnt signaling through Lrp5 is an important component of normal mammary stem cell function.

  4. PERIANTH DEVELOPMENT IN THE BASAL MONOCOT TRIGLOCHIN MARITIMA (JUNCAGINACEAE)

    DEFF Research Database (Denmark)

    Buzgo, Matyas; Soltis, Douglas E.; Soltis, Pamela S.;

    2006-01-01

    Basal monocots exhibit considerable variation in inflorescence and floral structure. In some cases, such as Triglochin maritima, it is not clear whether the lateral and terminal structures of the inflores- cence are flowers or pseudanthia, or where the limits between flowers and inflorescence lie...

  5. Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review

    Science.gov (United States)

    Cohen, Philip R

    2016-01-01

    Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer. PMID:27738570

  6. Calibration of Partial Factors for Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Duijnen, P.G.; Schweckendiek, T.; Calle, E.O.F.; Van Eekelen, S.J.M.

    2015-01-01

    In the Netherlands, the design guideline for basal reinforced piled embankments has been revised (CUR226:2015) adopting a new analytical design model (The Concentric Arches (CA) model, Van Eekelen et al., 2013; 2015). The CA model provides geosynthetic reinforcement (GR) strains which were compared

  7. Mephedrone alters basal ganglia and limbic neurotensin systems.

    Science.gov (United States)

    German, Christopher L; Hoonakker, Amanda H; Fleckenstein, Annette E; Hanson, Glen R

    2014-08-01

    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters pre-synaptic dopamine (DA) activity like many psychostimulants. However, little is known about the post-synaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1 -like receptors in the striatum and the substantia nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.

  8. New common variants affecting susceptibility to basal cell carcinoma.

    NARCIS (Netherlands)

    Stacey, S.N.; Sulem, P.; Masson, G.; Gudjonsson, S.A.; Thorleifsson, G.; Jakobsdottir, M.; Sigurdsson, A.; Gudbjartsson, D.F.; Sigurgeirsson, B.; Benediktsdottir, K.R.; Thorisdottir, K.; Ragnarsson, R.; Scherer, D.; Hemminki, K.; Rudnai, P.; Gurzau, E.; Koppova, K.; Botella-Estrada, R.; Soriano, V.; Juberias, P.; Saez, B.; Gilaberte, Y.; Fuentelsaz, V.; Corredera, C.; Grasa, M.; Hoiom, V.; Lindblom, A.; Bonenkamp, J.J.; Rossum, M.M. van; Aben, K.K.H.; Vries, E. de; Santinami, M.; Mauro, M.G. Di; Maurichi, A.; Wendt, J.; Hochleitner, P.; Pehamberger, H.; Gudmundsson, J.; Magnusdottir, D.N.; Gretarsdottir, S.; Holm, H.; Steinthorsdottir, V.; Frigge, M.L.; Blondal, T.; Saemundsdottir, J.; Bjarnason, H.; Kristjansson, K.; Bjornsdottir, G.; Okamoto, I.; Rivoltini, L.; Rodolfo, M.; Kiemeney, L.A.L.M.; Hansson, J.; Nagore, E.; Mayordomo, J.I.; Kumar, R.; Karagas, M.R.; Nelson, H.H.; Gulcher, J.R.; Rafnar, T.; Thorsteinsdottir, U.; Olafsson, J.H.; Kong, A.; Stefansson, K.

    2009-01-01

    In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A vari

  9. Utilizing Psycholinguistic Insights in Teaching via the Basal Reader.

    Science.gov (United States)

    Newman, Harold

    Ideas of educational psycholinguists Frank Smith and Kenneth Goodman can be combined with the ideas presented in current basal reader manuals to help teachers teach reading more effectively. Since reading and speaking are parallel processes, teachers may invite children to "read" with them, hearing the melody of language as they point to…

  10. Redefinition and global estimation of basal ecosystem respiration rate

    DEFF Research Database (Denmark)

    Yuan, Wenping; Luo, Yiqi; Li, Xianglan;

    2011-01-01

    Basal ecosystem respiration rate (BR), the ecosystem respiration rate at a given temperature, is a common and important parameter in empirical models for quantifying ecosystem respiration (ER) globally. Numerous studies have indicated that BR varies in space. However, many empirical ER models sti...

  11. Saccade learning with concurrent cortical and subcortical basal ganglia loops

    Directory of Open Access Journals (Sweden)

    Steve eN'guyen

    2014-04-01

    Full Text Available The Basal Ganglia is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks.We propose a model of saccade generation with reinforcement learning capabilities based onour previous basal ganglia and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of thesaccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks.The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not. Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate.

  12. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia;

    2015-01-01

    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing of...

  13. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    Science.gov (United States)

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated drugs, such as camptothecin, imazalil, itraconazole, hygromycin, and 4-nitroquinoline oxide. We also verified the relative transcript levels of the Atr genes in the A. nidulans imazalil-resistant mutants. These genes displayed a very complex pattern in different ima genetic backgrounds. The imaB mutant has higher basal transcript levels of AtrB and -D than those of the wild-type strain. The levels of these two genes are comparable when the imaB mutant is grown in the presence and absence of imazalil. The imaC, -D, and -H mutants have higher basal levels of AtrA than that of the wild type. The same behavior is observed for the relative transcript levels of AtrB in the imaG mutant background. PMID:11872487

  14. Basal jawed vertebrate phylogenomics using transcriptomic data from Solexa sequencing.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available The traditionally accepted relationships among basal jawed vertebrates have been challenged by some molecular phylogenetic analyses based on mitochondrial sequences. Those studies split extant gnathostomes into two monophyletic groups: tetrapods and piscine branch, including Chondrichthyes, Actinopterygii and sarcopterygian fishes. Lungfish and bichir are found in a basal position on the piscine branch. Based on transcriptomes of an armored bichir (Polypterus delhezi and an African lungfish (Protopterus sp. we generated, expressed sequences and whole genome sequences available from public databases, we obtained 111 genes to reconstruct the phylogenetic tree of basal jawed vertebrates and estimated their times of divergence. Our phylogenomic study supports the traditional relationship. We found that gnathostomes are divided into Chondrichthyes and the Osteichthyes, both with 100% support values (posterior probabilities and bootstrap values. Chimaeras were found to have a basal position among cartilaginous fishes with a 100% support value. Osteichthyes were divided into Actinopterygii and Sarcopterygii with 100% support value. Lungfish and tetrapods form a monophyletic group with 100% posterior probability. Bichir and two teleost species form a monophyletic group with 100% support value. The previous tree, based on mitochondrial data, was significantly rejected by an approximately unbiased test (AU test, p = 0. The time of divergence between lungfish and tetrapods was estimated to be 391.8 Ma and the divergence of bichir from pufferfish and medaka was estimated to be 330.6 Ma. These estimates closely match the fossil record. In conclusion, our phylogenomic study successfully resolved the relationship of basal jawed vertebrates based on transtriptomes, EST and whole genome sequences.

  15. The non-active stellar chromosphere: Ca II basal flux

    Science.gov (United States)

    Pérez Martínez, M. I.; Schröder, K.-P.; Hauschildt, P.

    2014-11-01

    We analyse high-resolution, high-s/n European Southern Observatories (ESO)-archive spectra (from UVES, the UV echelle spectrograph) of 76 inactive or modestly active stars of spectral type G to M, main sequence and giants. Using PHOENIX model photospheres with Ca II K lines that match the observed line profiles, we (i) revise the effective temperatures, (ii) obtain a precise surface flux scale for each star and (iii) directly determine the exact surface fluxes of each Ca II K chromospheric emission with respect to the photospheric line profile. We find that our stellar sample exhibits a lower boundary to its chromospheric surface flux distribution with an unprecedented definition. From a subsample of the 25 least active stars, we obtain a simple empirical formula for the basal Ca II flux as a function of effective temperature: log {F^basal_{Ca II(H+K)}} = 7.05(± 0.31) log {T_eff} - 20.86(± 1.15). This is in good agreement with the Mg II basal flux. In a direct comparison with the large body of Mt Wilson S-measurements of the chromospheric Ca II emission and its well-defined cut-off, excellent agreement is achieved as well. A new result, however, is the small scatter of the least active star's fluxes about the basal flux. It is about 25 per cent and equals the residual uncertainties of our approach. At the same time, we do not find any evidence for a gravity dependence within these limits. This strongly confirms the basal flux as a well-defined and universal phenomenon, which characterizes every inactive chromosphere.

  16. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chang

    Full Text Available Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR, while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5 transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death.

  17. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  18. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...

  19. Diminution of prolactin and increase of thyrotrophin response to thyrotrophin releasing hormone occurring independently of changes in basal level of these hormones during treatment of hypothyroidism.

    Science.gov (United States)

    van Groenendael, J H; Fischer, H R; Hackeng, W H; Schopman, W; Silberbusch, J

    1983-08-01

    In order to study the effect of rising thyroid hormone levels in hypothyroidism upon prolactin responses to TRH, in relation to changes in basal prolactin concentration and to changes in TSH responses, we followed 18 patients by performing TRH tests before and after 14, 28, 42 and 56 d on gradually increasing levothyroxine dosages, plus a final test when euthyroidism was achieved. Basal prolactin rose initially, at day 14, followed by a return on days 28, 42 and 56 to a level similar to the pretherapeutic value, while at euthyroidism prolactin had fallen below the original value. The area under the prolactin response curve on TRH stimulation was unchanged at 14 d, notwithstanding the rise of basal prolactin concentration. At 28, 42 and 56 d the responses declined progressively along with basal prolactin concentrations that remained equivalent to the pretreatment level. The TSH response to TRH rose at 14, 28, and 42 d along with a continuous downward course of basal TSH. Thus, substitution with L-thyroxine inhibited the responsivity of prolactin but enhanced that of TSH to TRH. The fact that these changes occurred in opposite directions, appears to rule out a negative feed-back effect of T4 on hypothalamic TRH secretion. The effects on responses were shown to occur independently of those on basal secretion of prolactin and TSH. PMID:6411393

  20. Initial Study

    DEFF Research Database (Denmark)

    Torp, Kristian

    2009-01-01

    Congestion is a major problem in most cities and the problem is growing (Quiroga, 2000) (Faghri & Hamad, 2002). When the congestion level is increased the drivers notice this as delays in the traffic (Taylor, Woolley, & Zito, 2000), i.e., the travel time for the individual driver is simply...... increased. In the initial study presented here, the time it takes to pass an intersection is studied in details. Two major signal-controlled four-way intersections in the center of the city Aalborg are studied in details to estimate the congestion levels in these intersections, based on the time it takes...

  1. Rill Initiation

    OpenAIRE

    Ottosen, Thor-Bjørn

    2008-01-01

    This project is about rill erosion. The aim is to test whether rill initiation can be predicted from the shear strength of the soil as measured with a torvane on saturated soil. This approach was set forward by Rauws and Govers 1988. Rainfall simulation experiments are conducted at a plot size 2x1m, performed in May on the Marbjerg experimental field. The results are evaluated using a chain set to measure alterations of the surface roughness as a result of the erosion, visual evaluation of ph...

  2. Effects of the Basal Boundary on Debris-flow Dynamics

    Science.gov (United States)

    Iverson, R. M.; Logan, M.; Lahusen, R. G.; Berti, M.

    2006-12-01

    Data aggregated from 37 large-scale experiments reveal some counterintuitive effects of bed roughness on debris-flow dynamics. In each experiment 10 m3 of water-saturated sand and gravel, mixed with 1 to 12% silt and clay by dry weight, was abruptly released from a gate at the head of a 2-m wide, 1.2-m deep, 82.5-m long rectangular flume inclined 31° throughout most of its length and adjoined to a gently sloping, planar runout surface at its toe. The flume's basal boundary consisted of either a smooth, planar concrete surface or a concrete surface roughened with a grid of conical bumps. Tilt-table tests with dry debris-flow sediment showed that this roughness imparted a basal friction angle of 38°, comparable to the sediment's internal friction angle of 38-42°, whereas the smooth-bed friction angle was 28°. About 20 electronic sensors installed in the flume yielded data on flow speeds and depths as well as basal stresses and pore pressures. Behavior observed in all experiments included development of steep, unsaturated, coarse-grained debris-flow snouts and tapering, liquefied, fine-grained tails. Flows on the rough bed were typically about 50% thicker and 20% slower than flows on the smooth bed, although the rough bed caused snout steepening that enabled flow fronts to move faster than expected, given the increased bed friction. Moreover, flows on rough beds ran out further than flows on smooth beds owing to enhanced grain-size segregation and lateral levee formation. With the rough bed, measured basal stresses and pore pressures differed little from values expected from static gravitational loading of partially liquefied debris. With the smooth bed, however, measured basal stresses and pore pressures were nearly twice as large as expected values. This anomaly resulted from flow disturbance at the upstream lips of steel plates in which sensors were mounted. The lips produced barely visible ripples in otherwise smooth flow surfaces, yet sufficed to generate

  3. Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB

    Institute of Scientific and Technical Information of China (English)

    SONG Hong-shuo; SHI Shuang; LU Xiao-zhi; GAO Feng; YAN Ling; WANG Ying; ZHUANG Hui

    2010-01-01

    Background The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking chemokines and TM4SF. Different members exhibit diverse biological functions. In this study, the effect of intracellular CMTM2 on regulating human immunodeficiency virus type-1 (HIV-1) transcription was evaluated.Methods The effects of CMTM2 on regulating full-length HIV-1 provirus and the HIV-1 long terminal repeat (LTR)-directed transcription were assessed by luciferase assay. Transcription factor assays, using the luciferase reporter plasmids of AP-1, CRE, and NF-κB were conducted to explore the signaling pathway(s) that may be regulated by CMTM2. The potential relationship between CMTM2 and the transcription factor AP-1 was further analyzed by Western blotting analyses to investigate the effect of CMTM2 on PMA-induced ERK1/2 phosphorylation.Results The results from the current study revealed that CMTM2 acts as a negative regulator of HIV-1 transcription.CMTM2 exerted a suppressive action on both full-length HIV-1 provirus and HIV-1 LTR-directed transcription.Transcription factor assays showed that CMTM2 selectively inhibited basal AP-1 and CREB activity. Co-expression of HIV-1 Tat, a potent AP-1 and CREB activator, can not reverse CMTM2-mediated AP-1 and CREB inhibition, suggesting a potent and specific effect of CMTM2 on negatively regulating these two signaling pathways.Conclusion Intracellular CMTM2 can negatively regulate HIV-1 transcription, at least in part, by targeting the AP-1 and CREB pathways. Exploring the mechanisms further may lead to new ways to control HIV-1 replication.

  4. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any a

  5. Automatic Music Transcription

    Science.gov (United States)

    Klapuri, Anssi; Virtanen, Tuomas

    Written musical notation describes music in a symbolic form that is suitable for performing a piece using the available musical instruments. Traditionally, musical notation indicates the pitch, target instrument, timing, and duration of each sound to be played. The aim of music transcription either by humans or by a machine is to infer these musical parameters, given only the acoustic recording of a performance.

  6. Recurrent peripheral odontogenic fibroma associated with basal cell budding.

    Science.gov (United States)

    Sreeja, C; Vezhavendan, N; Shabana, F; Vijayalakshmi, D; Devi, M; Arunakiry, N

    2014-07-01

    Peripheral odontogenic fibroma (POdF) is a rare benign odontogenic neoplasm. It represents the soft tissue counterpart of central odontogenic fibroma. The embryonic source of POdF has been suggested by many as arising from the rest of dental lamina that has persisted in the gingiva following its disintegration. It presents clinically as a firm, slow growing and sessile gingival mass, which is difficult to distinguish with more common inflammatory lesions. Very few cases of recurrence have been documented. It has been stated that histological budding of basal cell layer of the surface squamous epithelium is associated with higher recurrence and the presence of calcification in direct apposition to the epithelial rest is associated with lower recurrence. Hereby, we present a case which histologically exhibited budding of the basal cell layer, which could have been the reason for its recurrence. PMID:25210375

  7. Recurrent peripheral odontogenic fibroma associated with basal cell budding

    Directory of Open Access Journals (Sweden)

    C Sreeja

    2014-01-01

    Full Text Available Peripheral odontogenic fibroma (POdF is a rare benign odontogenic neoplasm. It represents the soft tissue counterpart of central odontogenic fibroma. The embryonic source of POdF has been suggested by many as arising from the rest of dental lamina that has persisted in the gingiva following its disintegration. It presents clinically as a firm, slow growing and sessile gingival mass, which is difficult to distinguish with more common inflammatory lesions. Very few cases of recurrence have been documented. It has been stated that histological budding of basal cell layer of the surface squamous epithelium is associated with higher recurrence and the presence of calcification in direct apposition to the epithelial rest is associated with lower recurrence. Hereby, we present a case which histologically exhibited budding of the basal cell layer, which could have been the reason for its recurrence.

  8. Body composition and basal metabolic rate in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, I M; Rytgaard, Helene Charlotte; Mogensen, U B;

    2016-01-01

    composition (e.g. abdominal fat) may be more so. Basal metabolic rate (BMR) is an expression of resting metabolism and may serve as a complementary tool when assessing the possibly underlying metabolism behind a persons' body composition. OBJECTIVE: To investigate the body composition and basal metabolic rate...... HS patients, a population-based HS group of 430 population HS patients, and 20 780 controls. Age- and sex-adjusted analyses showed a 10.12% (P ....0001) was significantly higher in HS patients compared with controls. Additionally, age and sex-adjusted analyses showed a higher predicted estimate of BMR for the HS groups compared with controls (154.56 kcal/day (95% CI 54.96-254.16) (P = 0.0031) for the hospital-based HS group, and 82.63 kcal/day (95%CI 59...

  9. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    N K Kiran

    2012-01-01

    Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  10. Morphological elucidation of basal ganglia circuits contributing reward prediction.

    Science.gov (United States)

    Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

    2015-01-01

    Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor-critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

  11. [Morphological Re-evaluation of the Basal Ganglia Network].

    Science.gov (United States)

    Fujiyama, Fumino

    2016-07-01

    Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to dopamine signals, via dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of reward prediction error and conducts reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor-critic model has been previously proposed and extended by the existence of role sharing within the striatum, with particular focus on the striosome and matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome and matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:27395470

  12. 基底节性失语%Basal Ganglia Aphasia

    Institute of Scientific and Technical Information of China (English)

    隆昱洲; 柳华; 艾青龙

    2008-01-01

    基底节病变常导致语言功能障碍,其表现彤式复杂,既可出现口语语言障碍,也可出现书面语语言障碍,几乎包括所有失语类型.文章就基底节解剖、基底节失语的定义、特点、机制以及病变部位对语言的影响做了综述.%Basal ganglion lesions often result in language impairment. Its patterns of manifestation are complicated. Patients may either have oral language disorders or written language disorders, which almost includes all types of aphasia, The article reviews the anatomy, definition, feature and mechanisms of basal ganglia aphasia as well as the effect of lesion sites on language.

  13. Is Broca's area part of a basal ganglia thalamocortical circuit?

    Science.gov (United States)

    Ullman, Michael T

    2006-05-01

    The cortex constituting Broca's area does not exist in isolation. Rather, like other cortical regions, Broca's area is connected to other brain structures, which likely play closely related functional roles. This paper focuses on the basal ganglia, a set of subcortical structures that project through topographically organized "channels" via the thalamus to different frontal regions. It is hypothesized that the basal ganglia project to Broca's area. This circuitry is further posited to encompass at least two channels. One channel can be characterized as subserving procedural memory, while the other underlies the retrieval of knowledge from declarative memory. These hypotheses are supported by both anatomical and functional evidence. Implications and issues for further investigation are discussed. PMID:16881254

  14. Deformation Studies of NEEM, Greenland Basal Folded Ice

    Science.gov (United States)

    Keegan, K.; Dahl-Jensen, D.; Montagnat, M.; Weikusat, I.

    2015-12-01

    Deep Greenland ice cores and airborne radio echo sounding (RES) images have recently revealed that basal ice flow of the Greenland Ice Sheet is very unstable. In many locations, a basal layer of disturbed ice is observed. At the NEEM, Greenland site this folding occurs at the boundary between the Eemian and glacial ice regimes, indicating that differences in physical properties of the ice play a role in the disturbance. Past work in metallurgy and ice suggests that impurity content controls grain evolution and therefore deformation. We hypothesize that the differences in ice flow seen deep in the NEEM ice core are controlled by differences in the impurity content of the ice layers. Here we present results of fabric, grain size, impurity content, and deformation studies from samples above and below this unstable boundary in the ice sheet.

  15. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros

    2015-11-01

    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  16. Basal resistance for three of the largest Greenland outlet glaciers

    Science.gov (United States)

    Shapero, Daniel R.; Joughin, Ian R.; Poinar, Kristin; Morlighem, Mathieu; Gillet-Chaulet, Fabien

    2016-01-01

    Resistance at the ice-bed interface provides a strong control on the response of ice streams and outlet glaciers to external forcing, yet it is not observable by remote sensing. We used inverse methods constrained by satellite observations to infer the basal resistance to flow underneath three of the Greenland Ice Sheet's largest outlet glaciers. In regions of fast ice flow and high (>250 kPa) driving stresses, ice is often assumed to flow over a strong bed. We found, however, that the beds of these three glaciers provide almost no resistance under the fast-flowing trunk. Instead, resistance to flow is provided by the lateral margins and stronger beds underlying slower-moving ice upstream. Additionally, we found isolated patches of high basal resistivity within the predominantly weak beds. Because these small-scale (tested their robustness to different degrees of regularization.

  17. Cerebellar networks with the cerebral cortex and basal ganglia.

    Science.gov (United States)

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2013-05-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent findings from neuroanatomical, behavioral, and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that cerebellar output reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, which suggests that the two subcortical structures are part of a densely interconnected network. Taken together, these findings elucidate the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  18. Basal Cell Carcinoma of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Masahiro Nakayama

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC is a malignant neoplasm derived from nonkeratinizing cells that originate from the basal layer of the epidermis and is the most frequent type of skin cancer in humans, with cumulative exposure to ultraviolet radiation as an important risk factor. BCC occurs most frequently at sun-exposed sites, with the head and neck being common areas. Tumors can be classified as nodular, superficial, morpheaform, infiltrating, metatypic, and fibroepithelioma of Pinkus. Several treatment options such as surgical excision and nonsurgical procedures are available. The choice of treatment should be determined based on the histological subtype of a lesion, cost, its size and location, patient age, medical condition of the patient, treatment availability, and the patient's wishes. The aim of any therapy selected for BCC treatment involving the head and neck is to ensure complete removal, the preservation of function, and a good cosmetic outcome.

  19. LATE PRESENTATION OF BASAL CELL CARCINOMA - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Phani Kumar

    2013-12-01

    Full Text Available PURPOSE: To present a case of basal cell carcinoma with late presentation. METHODS: A 55year - old woman with gradual progressive, nodular, small brown lesion at the left lower eye lid for past 3 years was examined with, computed tomography (CT and then Excisional biopsy was done. RESULTS: The presenting symptom s of the patient were gradual progressive, nodular, sma ll brown lesion at the left lower eye lid . Excisional bi opsy with frozen section of the lesion was performed. Histopathologic evaluation of the eyelid lesion disclosed Trichoblastic (basal cell carcinoma of lower eye lid with large nodular and cribiform (a denoid patterns without any lymph - vascula r and perineural invasion. Post - operative period was uneventful. CONCLUSION: We are hereby reporting this case of eyelid BCC, with no history of skin cancer, or radiation treatment but exposure to sunlight. With earl y adequate treatment the prognosis is good KEYWORDS: B asal cell carcinoma, Excisional biopsy, Trichoblastic carcinoma .

  20. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

    Science.gov (United States)

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

    2015-01-01

    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr's disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly presents with mental damage, convulsion, parkinson-like clinical picture, and neuropsychiatric behavior disorders; however, presentation with impulse control disorder is not a frequent presentation. In the current report, a 43-year-old male patient who has been admitted to psychiatry policlinic with the complaints of aggressive behavior episodes and who has been diagnosed with impulse control disorder and IBGC was evaluated in the light of the literature. PMID:26246920

  1. Novel Hedgehog pathway targets against Basal Cell Carcinoma

    OpenAIRE

    Tang, Jean Y.; So, Po-Lin; Epstein, Ervin H.

    2006-01-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastro-intestinal, and other cancers. This review will provide an overvi...

  2. ATG7 contributes to plant basal immunity towards fungal infection

    OpenAIRE

    Heike D. Lenz; Vierstra, Richard D.; Nürnberger, Thorsten; Gust, Andrea A.

    2011-01-01

    Autophagy has an important function in cellular homeostasis. In recent years autophagy has been implicated in plant basal immunity and assigned negative (“anti-death”) and positive (“pro-death”) regulatory functions in controlling cell death programs that establish sufficient immunity to microbial infection. We recently showed that Arabidopsis mutants lacking the autophagy-associated (ATG) genes ATG5, ATG10 and ATG18a are compromised in their resistance towards infection with necrotrophic fun...

  3. BASAL CELL CARCINOMA OF THE NOSE—Treatment with Chemosurgery

    Science.gov (United States)

    Beirne, Gilbert A.; Beirne, Clinton G.

    1956-01-01

    Basal cell carcinomas of the nose probably originate from embryologic cell rests left between cartilages and bones in the fusion and migration of the nasal precursors. Some carcinomas have been found to invade to the mucosal surface between subcutaneous structures or around the alar margins. Recurrences are particularly likely to develop deep extensions due to overlying scar tissue. In many cases, chemosurgical removal has disclosed unsuspected deep and lateral extensions. It is the treatment method of choice for many such lesions. PMID:13276824

  4. Subsystems of the basal ganglia and motor infrastructure

    OpenAIRE

    Kamali Sarvestani, Iman

    2013-01-01

    The motor nervous system is one of the main systems of the body and is our principle means ofbehavior. Some of the most debilitating and wide spread disorders are motor systempathologies. In particular the basal ganglia are complex networks of the brain that control someaspects of movement in all vertebrates. Although these networks have been extensively studied,lack of proper methods to study them on a system level has hindered the process ofunderstanding what they do and how they do it. In ...

  5. Translating structure to clinical properties of an ideal basal insulin.

    Science.gov (United States)

    Unnikrishnan, A G; Bantwal, Ganapathi; Sahay, R K

    2014-01-01

    There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

  6. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

    Science.gov (United States)

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-12-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  7. Methylation of an intragenic alternative promoter regulates transcription of GARP.

    Science.gov (United States)

    Haupt, Sonja; Söntgerath, Viktoria Sophie Apollonia; Leipe, Jan; Schulze-Koops, Hendrik; Skapenko, Alla

    2016-02-01

    Alternative promoter usage has been proposed as a mechanism regulating transcriptional and translational diversity in highly elaborated systems like the immune system in humans. Here, we report that transcription of human glycoprotein A repetitions predominant (GARP) in regulatory CD4 T cells (Tregs) is tightly regulated by two alternative promoters. An intragenic promoter contains several CpGs and acts as a weak promoter that is demethylated and initiates transcription Treg-specifically. The strong up-stream promoter containing a CpG-island is, in contrast, fully demethylated throughout tissues. Transcriptional activity of the strong promoter was surprisingly down-regulated upon demethylation of the weak promoter. This demethylation-induced transcriptional attenuation regulated the magnitude of GARP expression and correlated with disease activity in rheumatoid arthritis. Treg-specific GARP transcription was initiated by synergistic interaction of forkhead box protein 3 (Foxp3) with nuclear factor of activated T cells (NFAT) and was underpinned by permissive chromatin remodeling caused by release of the H3K4 demethylase, PLU-1. Our findings describe a novel function of alternative promoters in regulating the extent of transcription. Moreover, since GARP functions as a transporter of transforming growth factor β (TGFβ), a cytokine with broad pleiotropic traits, GARP transcriptional attenuation by alternative promoters might provide a mechanism regulating peripheral TGFβ to avoid unwanted harmful effects.

  8. The Arabidopsis Mediator Complex Subunit16 Is a Key Component of Basal Resistance against the Necrotrophic Fungal Pathogen Sclerotinia sclerotiorum.

    Science.gov (United States)

    Wang, Chenggang; Yao, Jin; Du, Xuezhu; Zhang, Yanping; Sun, Yijun; Rollins, Jeffrey A; Mou, Zhonglin

    2015-09-01

    Although Sclerotinia sclerotiorum is a devastating necrotrophic fungal plant pathogen in agriculture, the virulence mechanisms utilized by S. sclerotiorum and the host defense mechanisms against this pathogen have not been fully understood. Here, we report that the Arabidopsis (Arabidopsis thaliana) Mediator complex subunit MED16 is a key component of basal resistance against S. sclerotiorum. Mutants of MED16 are markedly more susceptible to S. sclerotiorum than mutants of 13 other Mediator subunits, and med16 has a much stronger effect on S. sclerotiorum-induced transcriptome changes compared with med8, a mutation not altering susceptibility to S. sclerotiorum. Interestingly, med16 is also more susceptible to S. sclerotiorum than coronatine-insensitive1-1 (coi1-1), which is the most susceptible mutant reported so far. Although the jasmonic acid (JA)/ethylene (ET) defense pathway marker gene PLANT DEFENSIN1.2 (PDF1.2) cannot be induced in either med16 or coi1-1, basal transcript levels of PDF1.2 in med16 are significantly lower than in coi1-1. Furthermore, ET-induced suppression of JA-activated wound responses is compromised in med16, suggesting a role for MED16 in JA-ET cross talk. Additionally, MED16 is required for the recruitment of RNA polymerase II to PDF1.2 and OCTADECANOID-RESPONSIVE ARABIDOPSIS ETHYLENE/ETHYLENE-RESPONSIVE FACTOR59 (ORA59), two target genes of both JA/ET-mediated and the transcription factor WRKY33-activated defense pathways. Finally, MED16 is physically associated with WRKY33 in yeast and in planta, and WRKY33-activated transcription of PDF1.2 and ORA59 as well as resistance to S. sclerotiorum depends on MED16. Taken together, these results indicate that MED16 regulates resistance to S. sclerotiorum by governing both JA/ET-mediated and WRKY33-activated defense signaling in Arabidopsis.

  9. Photodynamic therapy for basal cell skin cancer ENT-organs

    Directory of Open Access Journals (Sweden)

    V. N. Volgin

    2014-01-01

    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  10. Photosynthate partitioning in basal zones of tall fescue leaf blades

    International Nuclear Information System (INIS)

    Elongating grass leaves have successive zones of cell division, cell elongation, and cell maturation in the basal portion of the blade and are a strong sink for photosynthate. Our objective was to determine dry matter (DM) deposition and partitioning in basal zones of elongating tall fescue (Festuca arundinacea Schreb.) leaf blades. Vegetative tall fescue plants were grown in continuous light (350 micromoles per square meter per second photosynthetic photon flux density) to obtain a constant spatial distribution of elongation growth with time. Content and net deposition rates of water-soluble carbohydrates (WSC) and DM along elongating leaf blades were determined. These data were compared with accumulation of 14C in the basal zones following leaf-labeling with 14CO2. Net deposition of DM was highest in the active cell elongation zone, due mainly to deposition of WSC. The maturation zone, just distal to the elongation zone, accounted for 22% of total net deposition of DM in elongating leaves. However, the spatial profile of 14C accumulation suggested that the elongation zone and the maturation zone were sinks of equal strength. WSC-free DM accounted for 55% of the total net DM deposition in elongating leaf blades, but only 10% of incoming 14C-photosynthate accumulated in the water-insoluble fraction (WIF ∼ WSC-free DM) after 2 hours. In the maturation zone, more WSC was used for synthesis of WSC-free DM than was imported as recent photosynthate

  11. Basal forebrain thermoregulatory mechanism modulates auto-regulated sleep

    Directory of Open Access Journals (Sweden)

    Hruda N Mallick

    2012-06-01

    Full Text Available Regulation of body temperature and sleep are two physiological mechanisms that are vital for our survival. Interestingly neural structures implicated in both these functions are common. These areas include the medial preoptic area, the lateral preoptic area, the ventrolateral preoptic area, the median preoptic nucleus and the medial septum, which form part of the basal forebrain.When given a choice, rats prefer to stay at an ambient temperature of 270C, though the maximum sleep was observed when they were placed at 300C. Ambient temperature around 270C should be considered as the thermoneutral temperature for rats in all sleep studies. At this temperature the diurnal oscillations of sleep and body temperature are properly expressed. The warm sensitive neurons of the preoptic area mediate the increase in sleep at 300C. Promotion of sleep during the rise in ambient temperature from 270C to 300C, serve a thermoregulatory function. Autonomous thermoregulatory changes in core body temperature and skin temperature could act as an input signal to modulate neuronal activity in sleep-promoting brain areas. The studies presented here show that the neurons of the basal forebrain play a key role in regulating sleep. Basal forebrain thermoregulatory system is a part of the global homeostatic sleep regulatory mechanism, which is auto-regulated.

  12. Youth hypertension cerebral hemorrhage in basal ganglia surgery operation analysis

    Institute of Scientific and Technical Information of China (English)

    Qi-Hua Wang; Da-Shuang Lu; Jie Cui; Bo-Lin Qiao; Jing-Chun Wang

    2016-01-01

    Objective:Discuss surgical treatment of youth hypertension cerebral hemorrhage in basal ganglia.Methods:Retrospective analysis from January 2012 to April 2015 were adopted to bone flap craniotomy decompression for removal of hematoma and drainage drilling two kinds of surgical treatment of 46 cases of young patients with hypertension cerebral hemorrhage in basal ganglia.Results:Surgical operation, 28 patients postoperative review head CT, no further hemorrhage cases, residual hematoma volume 2-6 mL. Drilling drainage in the treatment of 18 patients, 1 case was bleeding again given surgical operation to remove the hematoma and the rest of the 17 cases without bleeding again, after 3 d, 17 cases of patients of postoperative hematoma drainage thoroughly. After 6 months, 46 cases of patients with postoperative review, GOS score light disability 9 cases, moderate disability 33 cases, 4 cases were severely disabled, curative effect is satisfied.Conclusions:Two kinds of operative methods each have advantages and disadvantages, young patients with hypertension cerebral hemorrhage in basal ganglia should according to patients' disease progression after speed, on admission patient's state of consciousness and head CT measured on admission hematoma volume, respectively.

  13. Pigmented basal cell carcinoma of the eyelid in Hispanics

    Directory of Open Access Journals (Sweden)

    Lily Koo Lin

    2008-10-01

    Full Text Available Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

  14. Proactive selective response suppression is implemented via the basal ganglia.

    Science.gov (United States)

    Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody; Aron, Adam R

    2013-08-14

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.

  15. Determinants of basal fat oxidation in healthy Caucasians.

    Science.gov (United States)

    Nagy, T R; Goran, M I; Weinsier, R L; Toth, M J; Schutz, Y; Poehlman, E T

    1996-05-01

    In a retrospective study, we examined several determinants of basal fat oxidation in 720 healthy Caucasian volunteers. Adult men (n = 427) and women (n = 293) were characterized for resting energy expenditure and substrate oxidation by indirect calorimetry (after a 12-h overnight fast), peak O2 consumption by a treadmill test to exhaustion, body composition by hydrodensitometry, food intake from a 3-day food diary, and hormonal status by fasting hormone concentrations. Fat oxidation was negatively correlated with fat mass in men (r = -0.11; P consumption and fat-free mass in men (model R2 = 0.142) and by free thyroxine, fat-free mass, and fasting insulin in women (model R2 = 0.153). Relative rates of fat oxidation (fat oxidation adjusted for differences in resting energy expenditure) were not correlated with fat mass in either gender. Women showed a lower rate of basal fat oxidation (both absolute and adjusted) than did men. Our results show that fat oxidation is not greater in individuals with a greater fat mass. Furthermore, our results support a sexual dimorphism in basal rates of fat oxidation. PMID:8727562

  16. Meige's syndrome associated with basal ganglia and thalamic functional disorders

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) or single positron emission computed tomography (SPECT) or both were performed and the responses of surface electromyography (EMG) were examined in seven cases of Meige's syndrome. MRI or SPECT or both demonstrated lesions of the basal ganglia, the thalamus, or both in five of the cases. Surface EMG revealed abnormal burst discharges in the orbicularis oculi and a failure of reciprocal muscular activity between the frontalis and orbicularis oculi in all the cases. These findings suggest that voluntary motor control and reciprocal activity in the basal ganglia-thalamocortical circuits are impaired in Meige's syndrome. In addition, good responses were seen to clonazepam, tiapride and trihexyphenidyl in these cases. Therefore, we conclude that dopaminergic, cholinergic, and γ-aminobutyric acid (GABA) ergic imbalances in the disorders of the basal ganglia and thalamus in Meige's syndrome cause control in the excitatory and inhibitory pathways to be lost, resulting in the failure of integration in reciprocal muscular activity and voluntary motor control. This failure subsequently causes the symptoms of Meige's syndrome. (author)

  17. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  18. Ancestral vascular lumen formation via basal cell surfaces.

    Directory of Open Access Journals (Sweden)

    Tomás Kucera

    Full Text Available The cardiovascular system of bilaterians developed from a common ancestor. However, no endothelial cells exist in invertebrates demonstrating that primitive cardiovascular tubes do not require this vertebrate-specific cell type in order to form. This raises the question of how cardiovascular tubes form in invertebrates? Here we discovered that in the invertebrate cephalochordate amphioxus, the basement membranes of endoderm and mesoderm line the lumen of the major vessels, namely aorta and heart. During amphioxus development a laminin-containing extracellular matrix (ECM was found to fill the space between the basal cell surfaces of endoderm and mesoderm along their anterior-posterior (A-P axes. Blood cells appear in this ECM-filled tubular space, coincident with the development of a vascular lumen. To get insight into the underlying cellular mechanism, we induced vessels in vitro with a cell polarity similar to the vessels of amphioxus. We show that basal cell surfaces can form a vascular lumen filled with ECM, and that phagocytotic blood cells can clear this luminal ECM to generate a patent vascular lumen. Therefore, our experiments suggest a mechanism of blood vessel formation via basal cell surfaces in amphioxus and possibly in other invertebrates that do not have any endothelial cells. In addition, a comparison between amphioxus and mouse shows that endothelial cells physically separate the basement membranes from the vascular lumen, suggesting that endothelial cells create cardiovascular tubes with a cell polarity of epithelial tubes in vertebrates and mammals.

  19. Transcriptional Regulation in Mammalian Cells by Sequence-Specific DNA Binding Proteins

    Science.gov (United States)

    Mitchell, Pamela J.; Tjian, Robert

    1989-07-01

    The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.

  20. Global analysis of transcriptionally engaged yeast RNA polymerase III reveals extended tRNA transcripts.

    Science.gov (United States)

    Turowski, Tomasz W; Leśniewska, Ewa; Delan-Forino, Clementine; Sayou, Camille; Boguta, Magdalena; Tollervey, David

    2016-07-01

    RNA polymerase III (RNAPIII) synthesizes a range of highly abundant small stable RNAs, principally pre-tRNAs. Here we report the genome-wide analysis of nascent transcripts attached to RNAPIII under permissive and restrictive growth conditions. This revealed strikingly uneven polymerase distributions across transcription units, generally with a predominant 5' peak. This peak was higher for more heavily transcribed genes, suggesting that initiation site clearance is rate-limiting during RNAPIII transcription. Down-regulation of RNAPIII transcription under stress conditions was found to be uneven; a subset of tRNA genes showed low response to nutrient shift or loss of the major transcription regulator Maf1, suggesting potential "housekeeping" roles. Many tRNA genes were found to generate long, 3'-extended forms due to read-through of the canonical poly(U) terminators. The degree of read-through was anti-correlated with the density of U-residues in the nascent tRNA, and multiple, functional terminators can be located far downstream. The steady-state levels of 3'-extended pre-tRNA transcripts are low, apparently due to targeting by the nuclear surveillance machinery, especially the RNA binding protein Nab2, cofactors for the nuclear exosome, and the 5'-exonuclease Rat1. PMID:27206856

  1. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

    Science.gov (United States)

    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O

    2000-06-01

    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  2. Stratified basal diamicts and their implications for subglacial conditions in deeply incised bedrock troughs

    Science.gov (United States)

    Buechi, Marius W.; Menzies, John; Anselmetti, Flavio S.

    2016-04-01

    deposition scenario. The combined macro- and microscopic evidence suggests that the diamicts originate from a soft deformable glacier-bed, while the sorted interbeds indicate depositional periods of meltwater flow and ponding during local decoupling at the ice-bed interface. The accretionary character of the stacking pattern suggests a repeated switching between a coupled and decoupled state with partial sediment preservation. Decoupling may occur during flotation of the glacier due to insufficient drainage of the glacier bed, or may be initiated by obstacles on the glacier bed. High basal water pressures are in agreement with the large hydrological catchment in the distal portion of the paleo-glacier, paired with the topographic low formed by the overdeepened subglacial basin. The sediments are thus excellent records of subglacial conditions in overdeepened basins.

  3. The nature of mutations induced by replication–transcription collisions.

    Science.gov (United States)

    Sankar, T Sabari; Wastuwidyaningtyas, Brigitta D; Dong, Yuexin; Lewis, Sarah A; Wang, Jue D

    2016-07-01

    The DNA replication and transcription machineries share a common DNA template and thus can collide with each other co-directionally or head-on. Replication–transcription collisions can cause replication fork arrest, premature transcription termination, DNA breaks, and recombination intermediates threatening genome integrity. Collisions may also trigger mutations, which are major contributors to genetic disease and evolution. However, the nature and mechanisms of collision-induced mutagenesis remain poorly understood. Here we reveal the genetic consequences of replication–transcription collisions in actively dividing bacteria to be two classes of mutations: duplications/deletions and base substitutions in promoters. Both signatures are highly deleterious but are distinct from the previously well-characterized base substitutions in the coding sequence. Duplications/deletions are probably caused by replication stalling events that are triggered by collisions; their distribution patterns are consistent with where the fork first encounters a transcription complex upon entering a transcription unit. Promoter substitutions result mostly from head-on collisions and frequently occur at a nucleotide that is conserved in promoters recognized by the major σ factor in bacteria. This substitution is generated via adenine deamination on the template strand in the promoter open complex, as a consequence of head-on replication perturbing transcription initiation. We conclude that replication–transcription collisions induce distinct mutation signatures by antagonizing replication and transcription, not only in coding sequences but also in gene regulatory elements.

  4. Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Eun Yeong Choe

    2012-06-01

    Full Text Available BackgroundThe present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes.MethodsIn the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated.ResultsA total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c and glycated albumin were 8.5% (8.0% to 9.6% and 25.2±7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8±0.1%, P<0.001 and their postprandial glucose levels were decreased by 48.7±10.3 mg/dL (P<0.001. Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55, high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78, and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99, and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93 at baseline were independently associated with good responders whose A1c reduction was more than 0.5%.ConclusionThe authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen.

  5. Openness initiative

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, S.S. [Los Alamos National Lab., NM (United States)

    1995-12-31

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.

  6. Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M

    Directory of Open Access Journals (Sweden)

    Iyoko Katoh

    2011-11-01

    Full Text Available The human and Old World primate genomes possess conserved endogenous retrovirus sequences that have been implicated in evolution, reproduction, and carcinogenesis. Human endogenous retrovirus (HERV-K with 5′LTR-gag-pro-pol-env-rec/np9-3′LTR sequences represents the newest retrovirus family that integrated into the human genome 1 to 5 million years ago. Although a high-level expression of HERV-K in melanomas, breast cancers, and terato-carcinomas has been demonstrated, the mechanism of the lineage-specific activation of the long terminal repeat (LTR remains obscure. We studied chromosomal HERV-K expression in MeWo melanoma cells in comparison with the basal expression in human embryonic kidney 293 (HEK293 cells. Cloned LTR of HERV-K (HML-2.HOM was also characterized by mutation and transactivation experiments. We detected multiple transcriptional initiator (Inr sites in the LTR by rapid amplification of complementary DNA ends (5′ RACE. HEK293 and MeWo showed different Inr usage. The most potent Inr was associated with a TATA box and three binding motifs of microphthalmia-associated transcription factor (MITF. Both chromosomal HERV-K expression and the cloned LTR function were strongly activated in HEK293 by transfection with MITF-M, a melanocyte/melanoma–specific isoform of MITF. Coexpression of MITF and the HERV-K core antigen was detected in retinal pigmented epithelium by an immunofluorescence analysis. Although malignant melanoma lines MeWo, G361, and SK-MEL-28 showed enhanced HERV-K transcription compared with normal melanocytes, the level of MITF-M messenger RNA persisted from normal to transformed melanocytes. Thus, MITF-M may be a prerequisite for the pigmented cell lineage–specific function of HERV-K LTR, leading to the high-level expression in malignant melanomas.

  7. Crystal structure of the transcription factor sc-mtTFB offers insights into mitochondrial transcription

    OpenAIRE

    Schubot, Florian D; Chen, Chun-Jung; Rose, John P.; Dailey, Tamara A.; Dailey, Harry A.; Wang, Bi-Cheng

    2001-01-01

    Although it is commonly accepted that binding of mitochondrial transcription factor sc-mtTFB to the mitochondrial RNA polymerase is required for specific transcription initiation in Saccharomyces cerevisiae, its precise role has remained undefined. In the present work, the crystal structure of sc-mtTFB has been determined to 2.6 Å resolution. The protein consists of two domains, an N-terminal α/β-domain and a smaller domain made up of four α-helices. Contrary to previous predictions, sc-mtTFB...

  8. Basal cell carcinoma develops in contact with the epidermal basal cell layer - a three-dimensional morphological study.

    Science.gov (United States)

    Pirici, Ionica; Ciurea, Marius Eugen; Mîndrilă, Ion; Avrămoiu, Ioan; Pirici, Alexandru; Nicola, Monica Georgiana; Rogoveanu, Otilia Constantina

    2016-01-01

    Basal cell carcinoma is the most common malignant tumor of the skin, and it develops most frequently on the areas of the body that make its treatment and care extremely difficult, especially in cases of neglecting or aggressive growth and invasion. Both typical mild cases as well as locally aggressive tumor types do not tend to metastasize, and it has been postulated that they should share some common biological and morphological features that might explain this behavior. In this study, we have utilized a high-resolution three-dimensional reconstruction technique on pathological samples from 15 cases of common aggressive (fibrosing and adenoid types) and mild (superficial type) basal cell carcinomas, and showed that all these types shared contact points and bridges with the underlying basal cell layer of the epidermis or with the outmost layer of the hair follicle. The connections found had in fact the highest number for fibrosing type (100%), compared to the superficial (85.71%) and adenoid (55%) types. The morphology of the connection bridges was also different, adjacent moderate to abundant inflammatory infiltrate seeming to lead to a loss of basaloid features in these areas. For the adenoid type, tumor islands seemed to be connected also to each other more strongly, forming a common "tumor lace", and while it has been showed that superficial and fibrosing types have higher recurrence risks, all together these data might iterate a connection between the number of bridging points and the biological and clinical manifestation of this skin tumor. PMID:27151694

  9. SNFing HIV transcription

    Directory of Open Access Journals (Sweden)

    Bukrinsky Michael

    2006-08-01

    Full Text Available Abstract The SWI/SNF chromatin remodeling complex is an essential regulator of transcription of cellular genes. HIV-1 infection induces exit of a core component of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre-integration complex. Several recent papers published in EMBO Journal, Journal of Biological Chemistry, and Retrovirology provide new information regarding possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1 has an inhibitory effect on pre-integration steps of HIV replication, but also contributes to stimulation of Tat-mediated transcription. This stimulation involves displacement of the nucleosome positioned at the HIV promoter.

  10. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review.

    Science.gov (United States)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-06-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis. PMID:27398205

  11. Functional Neuroanatomy and Behavioural Correlates of the Basal Ganglia: Evidence from Lesion Studies

    Directory of Open Access Journals (Sweden)

    Peter Ward

    2013-01-01

    Full Text Available Introduction: The basal ganglia are interconnected with cortical areas involved in behavioural, cognitive and emotional processes, in addition to movement regulation. Little is known about which of these functions are associated with individual basal ganglia substructures.

  12. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne – case report and literature review

    OpenAIRE

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P.

    2016-01-01

    Key Clinical Message Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment‐resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.

  13. The YEATS family member GAS41 interacts with the general transcription factor TFIIF

    OpenAIRE

    Ruggieri Alessia; Schuetz Nicole; Habel Nunja C; Heisel Sabrina; Meese Eckart

    2010-01-01

    Abstract Background In eukaryotes the transcription initiation by RNA polymerase II requires numerous general and regulatory factors including general transcription factors. The general transcription factor TFIIF controls the activity of the RNA polymerase II both at the initiation and elongation stages. The glioma amplified sequence 41 (GAS41) has been associated with TFIIF via its YEATS domain. Results Using GST pull-down assays, we demonstrated that GAS41 binds to both, the small subunit (...

  14. Genome transcription/translation of segmented, negative-strand RNA viruses

    NARCIS (Netherlands)

    Geerts-Dimitriadou, C.

    2011-01-01

    The requirements for alignment of capped RNA leader sequences along the viral genome during influenza transcription initiation (“cap-snatching”) have long been an enigma. Previous work on Tomato spotted wilt virus (TSWV) transcription initiation has revealed that this virus displays a pr

  15. Transcriptional profiling of putative human epithelial stem cells

    Directory of Open Access Journals (Sweden)

    Koçer Salih S

    2008-07-01

    Full Text Available Abstract Background Human interfollicular epidermis is sustained by the proliferation of stem cells and their progeny, transient amplifying cells. Molecular characterization of these two cell populations is essential for better understanding of self renewal, differentiation and mechanisms of skin pathogenesis. The purpose of this study was to obtain gene expression profiles of alpha 6+/MHCI+, transient amplifying cells and alpha 6+/MHCI-, putative stem cells, and to compare them with existing data bases of gene expression profiles of hair follicle stem cells. The expression of Major Histocompatibility Complex (MHC class I, previously shown to be absent in stem cells in several tissues, and alpha 6 integrin were used to isolate MHCI positive basal cells, and MHCI low/negative basal cells. Results Transcriptional profiles of the two cell populations were determined and comparisons made with published data for hair follicle stem cell gene expression profiles. We demonstrate that presumptive interfollicular stem cells, alpha 6+/MHCI- cells, are enriched in messenger RNAs encoding surface receptors, cell adhesion molecules, extracellular matrix proteins, transcripts encoding members of IFN-alpha family proteins and components of IFN signaling, but contain lower levels of transcripts encoding proteins which take part in energy metabolism, cell cycle, ribosome biosynthesis, splicing, protein translation, degradation, DNA replication, repair, and chromosome remodeling. Furthermore, our data indicate that the cell signaling pathways Notch1 and NF-κB are downregulated/inhibited in MHC negative basal cells. Conclusion This study demonstrates that alpha 6+/MHCI- cells have additional characteristics attributed to stem cells. Moreover, the transcription profile of alpha 6+/MHCI- cells shows similarities to transcription profiles of mouse hair follicle bulge cells known to be enriched for stem cells. Collectively, our data suggests that alpha 6+/MHCI- cells

  16. Basal but not luminal mammary epithelial cells require PI3K/mTOR signaling for Ras-driven overgrowth.

    Science.gov (United States)

    Plichta, Kristin A; Mathers, Jessica L; Gestl, Shelley A; Glick, Adam B; Gunther, Edward J

    2012-11-15

    The mammary ducts of humans and mice are comprised of two main mammary epithelial cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of luminal MECs. Breast cancer subtypes show divergent clinical behavior that may reflect properties inherent in their MEC compartment of origin. How the response to a cancer-initiating genetic event is shaped by MEC subtype remains largely unexplored. Using the mouse mammary gland, we designed organotypic three-dimensional culture models that permit challenge of discrete MEC compartments with the same oncogenic insult. Mammary organoids were prepared from mice engineered for compartment-restricted coexpression of oncogenic H-RAS(G12V) together with a nuclear fluorescent reporter. Monitoring of H-RAS(G12V)-expressing MECs during extended live cell imaging permitted visualization of Ras-driven phenotypes via video microscopy. Challenging either basal or luminal MECs with H-RAS(G12V) drove MEC proliferation and survival, culminating in aberrant organoid overgrowth. In each compartment, Ras activation triggered modes of collective MEC migration and invasion that contrasted with physiologic modes used during growth factor-initiated branching morphogenesis. Although basal and luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies revealed divergent use of Ras effector pathways. Blocking either the phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin may critically determine the drug sensitivity profiles of mammary neoplasia. PMID:23010075

  17. Regulation of the Bcas1 and Baiap3 transcripts in the subthalamic nucleus in mice recovering from MPTP toxicity

    DEFF Research Database (Denmark)

    Lauridsen, J B; Johansen, J L; Rekling, J C;

    2011-01-01

    . This mouse specific recovery might be linked to transcriptional changes in the basal ganglia enabling mice to maintain normal motor function in spite of low striatal dopamine levels. Laser microdissection was used to isolate the subthalamic nucleus from mice 7 and 28 days following MPTP exposure. High...

  18. Transcription and processing of mitochondrial RNA in the human pathogen Acanthamoeba castellanii.

    Science.gov (United States)

    Accari, Jessica; Barth, Christian

    2015-07-01

    The size, structure, gene content and organisation of mitochondrial genomes can be highly diverse especially amongst the protists. We investigated the transcription and processing of the mitochondrial genome of the opportunistic pathogen Acanthamoeba castellanii and here we present a detailed transcription map of the 41.6 kb genome that encodes 33 proteins, 16 tRNAs and 2 rRNAs. Northern hybridisation studies identified six major polycistronic transcripts, most of which are co-transcriptionally processed into smaller mono-, di- and tricistronic RNAs. The maturation of the polycistronic transcripts is likely to involve endonucleolytic cleavage where tRNAs serve as processing signals. Reverse transcription polymerase chain reactions across the intervening regions between the six major polycistronic transcripts suggest that these transcripts were once part of an even larger transcript. Our findings indicate that the mitochondrial genome of A. castellanii is transcribed from only one or two promoters, very similar to the mode of transcription in the mitochondria of its close relative Dictyostelium discoideum, where transcription is known to occur from only a single transcription initiation site. Transcription initiation from a minimal number of promoters despite a large genome size may be an emerging trend in the mitochondria of protists.

  19. Uji Diagnostik Dermatoskopi Pada Pasien Karsinoma Sel Basal di RSUP. H. Adam Malik Medan

    OpenAIRE

    Rinanda, Fenni

    2015-01-01

    Background: Basal-cell carcinoma is a malignant neoplasm appeared from a non-keratinizing cell which comes from epidermic basal layer. Hispatological test to diagnose basal-cell carcinoma may give rise to uncomfortability and fear. Dermatoscopy test, on the other hand, constitutes a non-invasive, easy, and prompt test which may minimize risks that potentially occurs when conducting a biopsy. Objective: To find out dermatoscopy diagnostic test values in diagnosing basal-cell carcinoma. ...

  20. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. The post-transcriptional operon m...

  1. Regulation of MCP-1 gene transcription by Smads and HIV-1 Tat in human glial cells

    International Nuclear Information System (INIS)

    Expression of several cytokines involved in signal transduction such as TGFβ-1 and the inflammatory chemokines including MCP-1 is elevated during the course of AIDS progression. The enhancement of these cellular proteins in astrocytic cells is mediated, at least in part, by HIV-1 Tat protein. Here, we investigate the possible regulation of MCP-1 transcription by Tat and the Smad family of transcription factors whose activities are induced by the TGFβ-1 pathway. Results from transfection studies revealed that Smad-3 stimulates basal and Tat-mediated transcription of MCP-1 in human astrocytic cells. Smad-4, on the other hand, had no effect on the basal activity of the MCP-1 promoter, but showed the ability to decrease both Smad-3 and Tat-induced transcription of the MCP promoter. Results from protein-binding studies revealed the ability of both Smad-3 and Smad-4 to associate with the region of Tat spanning residues 1-40. Examination of the transcriptional activity of the various domains of Smad including MH1, at the N-terminus, and MH2, at the C-terminus of the protein indicated that neither MH1 or MH2 alone positively cooperate with Tat in modulating MCP-1 transcription. However, ectopic expression of MH1 and, more notably, MH2 severely suppressed transcriptional activation of MCP-1 by Tat in astrocytic cells. Binding studies revealed that similar to the full-length Smad protein, both MH1 and MH2 associate with Tat protein and that the residues between 1 and 40 of Tat are important for their interaction. These observations reveal a novel mechanism for Tat-mediated transcriptional activation via TGFβ signaling pathway and provide evidence for regulation of MCP-1 gene transcription by this signaling pathway in human astrocytic cells

  2. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J;

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise...... eliminate them. Studies in a range of inbred mouse strains as well as mast cell-depleted mice reconstituted with mast cell precursors support a functional link between histamine-staining dermal mast cells and the extent of susceptibility to UVB-induced systemic immunomodulation. Humans, like mouse strains....... We hypothesize that mast cells function in humans, as in mouse strains, by initiating immunosuppression following UV irradiation and, thereby, allowing a permissive environment for the development of BCC. Thus, a high dermal mast cell prevalence as demonstrable in buttock skin is a significant...

  3. Transcription regulation by distal enhancers: who's in the loop?

    Science.gov (United States)

    Stadhouders, Ralph; van den Heuvel, Anita; Kolovos, Petros; Jorna, Ruud; Leslie, Kris; Grosveld, Frank; Soler, Eric

    2012-01-01

    Genome-wide chromatin profiling efforts have shown that enhancers are often located at large distances from gene promoters within the noncoding genome. Whereas enhancers can stimulate transcription initiation by communicating with promoters via chromatin looping mechanisms, we propose that enhancers may also stimulate transcription elongation by physical interactions with intronic elements. We review here recent findings derived from the study of the hematopoietic system.

  4. Basal ganglia disorders studied by positron emission tomography

    International Nuclear Information System (INIS)

    Recent development of positron emitting radioligands has made it possible to investigate the alterations of neurotransmitter systems associated with basal ganglia disorders in vivo. The functional integrity of nigro-striatal dopaminergic terminals may be studied with [18F]6-fluoro-L-dopa ([18F]dopa), and striatal dopamine receptor density with suitable PET ligands. [18F]dopa uptake in the striatum (putamen) is markedly reduced in patients with Parkinson's disease (PD). [18F]dopa-PET is capable of detecting sub-clinical nigral dysfunction in asymptomatic patients with familial PD and those who become Parkinsonian on conventional doses of dopamine receptor antagonists. While putamen [18F]dopa uptake is reduced to a similar level in patients with multiple system atrophy (MSA) and PD, caudate [18F] dopa uptake is lower in MSA than PD. However, [18F]dopa PET cannot consistently distinguish MSA from PD because individual ranges of caudate [18F]dopa uptake overlap. D1 and D2 receptor binding is markedly reduced in the striatum (posterior putamen) of MSA patients. Therefore, dopamine receptor imaging is useful for the differential diagnosis of MSA and PD. Similar marked reductions in putamen and caudate [18F]dopa uptake have been observed in patients with progressive supranuclear palsy (PSP). Moderate reductions in D2 receptor binding have been reported in the striatum of PSP patients. The reduction in D2 receptor binding is more prominent in the caudate than putamen. Striatal [18F]dopa uptake is normal or only mildly reduced in patients with dopa responsive dystonia (DRD). D2 receptor binding is markedly reduced in patients with Huntington's disease, while striatal [18F]dopa uptake is normal or mildly reduced. In summary, PET can demonstrate characteristic patterns of disruption of dopaminergic systems associated with basal ganglia disorders. These PET findings are useful in the differential diagnosis of basal ganglia disorders. (J.P.N.) 55 refs

  5. Expression of stromelysin 3 in basal cell carcinomas.

    Science.gov (United States)

    Cribier, B; Noacco, G; Peltre, B; Grosshans, E

    2001-01-01

    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  6. A phylogenomic approach to resolve the basal pterygote divergence.

    Science.gov (United States)

    Simon, Sabrina; Strauss, Sascha; von Haeseler, Arndt; Hadrys, Heike

    2009-12-01

    One of the most fascinating Bauplan transitions in the animal kingdom was the invention of insect wings, a change that also contributed to the success and enormous diversity of this animal group. However, the origin of insect flight and the relationships of basal winged insect orders are still controversial. Three hypotheses have been proposed to explain the phylogeny of winged insects: 1) the traditional Palaeoptera hypothesis (Ephemeroptera + Odonata, Neoptera), 2) the Metapterygota hypothesis (Ephemeroptera, Odonata + Neoptera), and 3) the Chiastomyaria hypothesis (Odonata, Ephemeroptera + Neoptera). Neither phylogenetic analyses of single genes nor even multiple marker systems (e.g., molecular markers + morphological characters) have yet been able to conclusively resolve basal pterygote divergences. A possible explanation for the lack of resolution is that the divergences took place in the mid-Devonian within a short period of time and attempts to solve this problem have been confounded by the major challenge of finding molecular markers to accurately track these short ancient internodes. Although phylogenomic data are available for Neoptera and some wingless (apterygote) orders, they are lacking for the crucial Odonata and Ephemeroptera orders. We adopt a multigene approach including data from two new expressed sequence tag projects-from the orders Ephemeroptera (Baetis sp.) and Odonata (Ischnura elegans)-to evaluate the potential of phylogenomic analyses in clarifying this unresolved issue. We analyzed two data sets that differed in represented taxa, genes, and overall sequence lengths: maxspe (15 taxa, 125 genes, and 31,643 amino acid positions) and maxgen (8 taxa, 150 genes, and 42,541 amino acid positions). Maximum likelihood and Bayesian inference analyses both place the Odonata at the base of the winged insects. Furthermore, statistical hypotheses testing rejected both the Palaeoptera and the Metapterygota hypotheses. The comprehensive molecular data set

  7. Characterization of a novel radiation-inducible transcript, uscA, and analysis of its transcriptional regulation

    International Nuclear Information System (INIS)

    The transcriptional expression of the uscA promote (PuscA) only occurred under aerobic conditions and a dose of 2Gy maximally activated transcription of PuscA. However, various environmental stress including physical shocks (pH, temperature, osmotic shock), DNA damaging agents (UV and MMC) or oxidative stressagents (paraquat, menadione, and H2O2) didn't cause the transcriptional activationof PuscA. The transcription of uscA was initiated at 170 bp upstream of the cyoA start codon, and ended around the ampG stop codon. The size of uscA was determined through reverse transcription assay, approximately 250 bp. The deletion analysis of uscA promoter demonstrates that radiation inducibility of PuscA is mediated by sequences present between -20 and +111 relativeto +1 of PuscA and radiation causes PuscA activation thorough permitting the expression that is repressed under non-irradiated conditions

  8. Polyphenol Compound as a Transcription Factor Inhibitor

    Directory of Open Access Journals (Sweden)

    Seyeon Park

    2015-10-01

    Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

  9. Interaction of Restin with transcription factors

    Institute of Scientific and Technical Information of China (English)

    WU; Yousheng; LU; Fan; QI; Yinxin; WANG; Ruihua; ZHANG; Jia

    2005-01-01

    Restin, a member of melanoma-associated antigen superfamily gene, was first cloned from differentiated leukemia cell induced by all trans-retinoic acid, and was able to inhibit cell proliferation, but the molecular mechanism was not clear. Since Restin was localized in cell nucleus, and its homolog member, Necdin (neuronal growth suppressor factor), could interact with transcription factors p53 and E2F1, we proposed that Restin might also function as Necdin through interacting with some transcription factors. In this study, transcription factors p53, AP1,ATFs and E2Fs were cloned and used in the mammalian two-hybrid system to identify their interaction with Restin. The results showed that only ATF3 had a strong interaction with Restin. It is interesting to know that ATF3 was an important transcription factor for G1 cell cycle initiation in physiological stress response. It was possible that the inhibition of cell proliferation by Restin might be related with the inhibition of ATF3 activity.

  10. Immune challenge affects basal metabolic activity in wintering great tits.

    OpenAIRE

    Ots, I.; Kerimov, A. B.; Ivankina, E. V.; Ilyina, T. A.; Hõrak, P.

    2001-01-01

    The costs of exploiting an organism's immune function are expected to form the basis of many life-history trade-offs. However, there has been debate about whether such costs can be paid in energetic and nutritional terms. We addressed this question in a study of wintering, free-living, male great tits by injecting them with a novel, non-pathogenic antigen (sheep red blood cells) and measuring the changes in their basal metabolic rates and various condition indices subsequent to immune challen...

  11. Cortico-basal ganglionic degeneration a case report

    Directory of Open Access Journals (Sweden)

    J. Teotônio de Oliveira

    1992-06-01

    Full Text Available The case of a Brazilian patient with cortico-basal ganglionic degeneration (CBGD is presented. Since three years ago, a 71-year old male displays asymmetric ideomotor apraxia, gait apraxia, cortical sensory impairment, myoclonus, limp dystonia and rigidity. His mental status is spared. There is neither consanguinity nor similar cases in his family. The differential diagnosis of CBGD is discussed. A brief review of the literature is made stressing the clinical and pathological features of CBGD. This disease is poorly known and probably underdiagnosed. Its diagnosis can be safely made based on clinical grounds.

  12. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia;

    2015-01-01

    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... defects than standard excisions with 4 or 6 mm margins. Closure of skin defects was achieved by side-to-side closure in 49% and by local flaps in 40%. There were no relapses during the observation time. The safety, cosmetic and functional outcome were excellent. CONCLUSIONS: We recommend that MMS...

  13. Delayed Diagnosis: Giant Basal Cell Carcinoma of Scalp

    Directory of Open Access Journals (Sweden)

    Didem Didar Balcı,

    2008-07-01

    Full Text Available Although basal cell carcinoma (BCC is the most common form of skin cancer, the scalp lesions of BCC have been rarely reported. Giant BCC is defined as a tumor larger than 5 cm in diameter and only 0.5-1 % of all BCCs achieve this size. We report a case of giant BCC on the scalp that was treated with topical coticosteroids and antifungal shampoo for five years. BCC should be considered in the differential diagnosis in erythematous plaque type lesions resistant to therapy with long duration localized on the scalp.

  14. Understanding Parkinsonian handwriting through a computational model of basal ganglia.

    Science.gov (United States)

    Gangadhar, Garipelli; Joseph, Denny; Chakravarthy, V Srinivasa

    2008-10-01

    Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease. PMID:18386983

  15. Transcriptional Activation of the Zygotic Genome in Drosophila.

    Science.gov (United States)

    Harrison, Melissa M; Eisen, Michael B

    2015-01-01

    During the first stages of metazoan development, the genomes of the highly specified sperm and egg must unite and be reprogrammed to allow for the generation of a new organism. This process is controlled by maternally deposited products. Initially, the zygotic genome is largely transcriptionally quiescent, and it is not until hours later that the zygotic genome takes control of development. The transcriptional activation of the zygotic genome is tightly coordinated with the degradation of the maternal products. Here, we review the current understanding of the processes that mediate the reprogramming of the early embryonic genome and facilitate transcriptional activation during the early stages of Drosophila development.

  16. Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells

    Science.gov (United States)

    Soung, Young Hwa; Pruitt, Kevin; Chung, Jun

    2014-01-01

    Arrestin domain-containing 3 (ARRDC3) is a tumor suppressor whose expression is either lost or suppressed in basal-like breast cancer (BLBC). However, the mechanism by which BLBC suppresses ARRDC3 expression is not established. Here, we show that expression of ARRDC3 in BLBC cells is suppressed at the transcriptional level. Suppression of ARRDC3 expression in BLBC cells involves epigenetic silencing as inhibitors of class III histone deacetylases (HDACs) significantly restores ARRDC3 levels in BLBC cells. SIRT2, among class III HDACs, plays a major role in epigenetic silencing of ARRDC3 in MDA-MB-231 cells. Acetylation levels of the ARRDC3 promoter in BLBC cells is significantly lower than that of other sub-types of BC cells. Chromatin immunopreciptitation analysis established SIRT2 binding at ARRDC3 promoter in BLBC cells. Our studies indicate that SIRT2 dependent epigenetic silencing of ARRDC3 is one of the important events that may contribute to the aggressive nature of BLBC cells.

  17. Idiopathic basal ganglia calcification-associated PDGFRB mutations impair the receptor signalling

    Science.gov (United States)

    Arts, Florence A; Velghe, Amélie I; Stevens, Monique; Renauld, Jean-Christophe; Essaghir, Ahmed; Demoulin, Jean-Baptiste

    2015-01-01

    Platelet-derived growth factors (PDGF) bind to two related receptor tyrosine kinases, which are encoded by the PDGFRA and PDGFRB genes. Recently, heterozygous PDGFRB mutations have been described in patients diagnosed with idiopathic basal ganglia calcification (IBGC or Fahr disease), a rare inherited neurological disorder. The goal of the present study was to determine whether these mutations had a positive or negative impact on the PDGFRB activity. We first showed that the E1071V mutant behaved like wild-type PDGFRB and may represent a polymorphism unrelated to IBGC. In contrast, the L658P mutant had no kinase activity and failed to activate any of the pathways normally stimulated by PDGF. The R987W mutant activated Akt and MAP kinases but did not induce the phosphorylation of signal transducer and activator of transcription 3 (STAT3) after PDGF stimulation. Phosphorylation of phospholipase Cγ was also decreased. Finally, we showed that the R987W mutant was more rapidly degraded upon PDGF binding compared to wild-type PDGFRB. In conclusion, PDGFRB mutations associated with IBGC impair the receptor signalling. PDGFRB loss of function in IBGC is consistent with recently described inactivating mutations in the PDGF-B ligand. These results raise concerns about the long-term safety of PDGF receptor inhibition by drugs such as imatinib. PMID:25292412

  18. Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome

    OpenAIRE

    Tian, Yuan; Voineagu, Irina; Paşca, Sergiu P; Won, Hyejung; Chandran, Vijayendran; Horvath, Steve; Dolmetsch, Ricardo E.; Geschwind, Daniel H.

    2014-01-01

    Background Common genetic variation and rare mutations in genes encoding calcium channel subunits have pleiotropic effects on risk for multiple neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. To gain further mechanistic insights by extending previous gene expression data, we constructed co-expression networks in Timothy syndrome (TS), a monogenic condition with high penetrance for ASD, caused by mutations in the L-type calcium channel, Cav1.2. Methods T...

  19. Temperature regulates transcription in the zebrafish circadian clock.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available It has been well-documented that temperature influences key aspects of the circadian clock. Temperature cycles entrain the clock, while the period length of the circadian cycle is adjusted so that it remains relatively constant over a wide range of temperatures (temperature compensation. In vertebrates, the molecular basis of these properties is poorly understood. Here, using the zebrafish as an ectothermic model, we demonstrate first that in the absence of light, exposure of embryos and primary cell lines to temperature cycles entrains circadian rhythms of clock gene expression. Temperature steps drive changes in the basal expression of certain clock genes in a gene-specific manner, a mechanism potentially contributing to entrainment. In the case of the per4 gene, while E-box promoter elements mediate circadian clock regulation, they do not direct the temperature-driven changes in transcription. Second, by studying E-box-regulated transcription as a reporter of the core clock mechanism, we reveal that the zebrafish clock is temperature-compensated. In addition, temperature strongly influences the amplitude of circadian transcriptional rhythms during and following entrainment by light-dark cycles, a property that could confer temperature compensation. Finally, we show temperature-dependent changes in the expression levels, phosphorylation, and function of the clock protein, CLK. This suggests a mechanism that could account for changes in the amplitude of the E-box-directed rhythm. Together, our results imply that several key transcriptional regulatory elements at the core of the zebrafish clock respond to temperature.

  20. Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters.

    Science.gov (United States)

    Yang, Chuhu; Bolotin, Eugene; Jiang, Tao; Sladek, Frances M; Martinez, Ernest

    2007-03-01

    The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that approximately 76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs - M3 (SCGGAAGY) and M22 (TGCGCANK) - that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only approximately 10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, approximately 46% of human core promoters contain the consensus INR (YYANWYY) and approximately 30% are INR-containing TATA-less genes. Significantly, approximately 46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present - and tend to cluster - in the transcription start site (TSS) region of approximately 40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic "housekeeping" processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription.

  1. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    in different cell types. This thesis presents several methods for analysis and description of promoters. We focus particularly the binding sites of TFs and computational methods for locating these. We contribute to the ¿eld by compiling a database of binding preferences for TFs which can be used for site...... published providing an unbiased overview of the transcription start site (TSS) usage in a tissue. We have paired this method with high-throughput sequencing technology to produce a library of unprecedented depth (DeepCAGE) for the mouse hippocampus. We investigated this in detail and focused particularly...

  2. Transcriptional changes during neuronal death and replacement in the olfactory epithelium.

    Science.gov (United States)

    Shetty, Ranjit S; Bose, Soma C; Nickell, Melissa D; McIntyre, Jeremy C; Hardin, Debra H; Harris, Andrew M; McClintock, Timothy S

    2005-12-01

    The olfactory epithelium has the unusual ability to replace its neurons.We forced replacement of mouse olfactory sensory neurons by bulbectomy. Microarray, bioinformatics, and in situ hybridization techniques detected a rapid shift in favor of pro-apoptotic proteins, a progressive immune response by macrophages and dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory sensory neurons, including gene silencing factors and sperm flagellar proteins. Transcripts encoding cell cycle regulators, axonogenesis proteins, and transcription factors and signaling proteins that promote proliferation and differentiation were increased at 5-7 days after bulbectomy and were expressed by basal progenitor cells or immature neurons. The transcription factors included Nhlhl, Hes6, Lmycl, c-Myc, Mxd4, Idl,Nmycl, Cited2, c-Myb, Mybll, Tead2, Dpl, Gata2, Lmol, and Soxll. The data reveal significant similarities with embryonic neurogenesis and make several mechanistic predictions, including the roles of the transcription factors in the olfactory sensory neuron lineage.

  3. Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression in rat hippocampus

    DEFF Research Database (Denmark)

    Lauterborn, J C; Poulsen, F R; Stinis, C T;

    1998-01-01

    Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon......-specific in situ hybridization was used to determine if adrenalectomy has differential effects on basal and activity-induced BDNF transcript expression in hippocampus. Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight increases in exon III-containing mRNA with 7-10-day survival...... no effect on exon IV-containing mRNA content. These results demonstrate that the negative effects of adrenal hormones on activity-induced BDNF expression are by far the greatest for transcripts containing exons I and II. Together with evidence for region-specific transcript expression, these results suggest...

  4. Insulin initiation in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vaag, Allan; Lund, Søren

    2012-01-01

    This review addresses the apparent disconnect between international guideline recommendations, real-life clinical practice and the results of clinical trials, with regard to the initiation of insulin using basal (long-acting) or premixed insulin analogues in patients with type 2 diabetes (T2D). E...

  5. Nascent transcription affected by RNA polymerase IV in Zea mays.

    Science.gov (United States)

    Erhard, Karl F; Talbot, Joy-El R B; Deans, Natalie C; McClish, Allison E; Hollick, Jay B

    2015-04-01

    All eukaryotes use three DNA-dependent RNA polymerases (RNAPs) to create cellular RNAs from DNA templates. Plants have additional RNAPs related to Pol II, but their evolutionary role(s) remain largely unknown. Zea mays (maize) RNA polymerase D1 (RPD1), the largest subunit of RNA polymerase IV (Pol IV), is required for normal plant development, paramutation, transcriptional repression of certain transposable elements (TEs), and transcriptional regulation of specific alleles. Here, we define the nascent transcriptomes of rpd1 mutant and wild-type (WT) seedlings using global run-on sequencing (GRO-seq) to identify the broader targets of RPD1-based regulation. Comparisons of WT and rpd1 mutant GRO-seq profiles indicate that Pol IV globally affects transcription at both transcriptional start sites and immediately downstream of polyadenylation addition sites. We found no evidence of divergent transcription from gene promoters as seen in mammalian GRO-seq profiles. Statistical comparisons identify genes and TEs whose transcription is affected by RPD1. Most examples of significant increases in genic antisense transcription appear to be initiated by 3'-proximal long terminal repeat retrotransposons. These results indicate that maize Pol IV specifies Pol II-based transcriptional regulation for specific regions of the maize genome including genes having developmental significance. PMID:25653306

  6. Basal Complex and Basal Venation of Odonata Wings: Structural Diversity and Potential Role in the Wing Deformation.

    Science.gov (United States)

    Rajabi, H; Ghoroubi, N; Malaki, M; Darvizeh, A; Gorb, S N

    2016-01-01

    Dragonflies and damselflies, belonging to the order Odonata, are known to be excellent fliers with versatile flight capabilities. The ability to fly over a wide range of speeds, high manoeuvrability and great agility are a few characteristics of their flight. The architecture of the wings and their structural elements have been found to play a major role in this regard. However, the precise influence of individual wing components on the flight performance of these insects remains unknown. The design of the wing basis (so called basal complex) and the venation of this part are responsible for particular deformability and specific shape of the wing blade. However, the wing bases are rather different in representatives of different odonate groups. This presumably reflects the dimensions of the wings on one hand, and different flight characteristics on the other hand. In this article, we develop the first three-dimensional (3D) finite element (FE) models of the proximal part of the wings of typical representatives of five dragonflies and damselflies families. Using a combination of the basic material properties of insect cuticle, a linear elastic material model and a nonlinear geometric analysis, we simulate the mechanical behaviour of the wing bases. The results reveal that although both the basal venation and the basal complex influence the structural stiffness of the wings, it is only the latter which significantly affects their deformation patterns. The use of numerical simulations enabled us to address the role of various wing components such as the arculus, discoidal cell and triangle on the camber formation in flight. Our study further provides a detailed representation of the stress concentration in the models. The numerical analysis presented in this study is not only of importance for understanding structure-function relationship of insect wings, but also might help to improve the design of the wings for biomimetic micro-air vehicles (MAVs). PMID:27513753

  7. Correlation transfer from basal ganglia to thalamus in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Pamela eReitsma

    2011-12-01

    Full Text Available Spike trains from neurons in the basal ganglia of parkinsonian primatesshow increased pairwise correlations, oscillatory activity, and burstrate compared to those from neurons recorded during normal brainactivity. However, it is not known how these changes affect the behaviorof downstream thalamic neurons. To understand how patterns ofbasal ganglia population activity may affect thalamic spike statistics,we study pairs of model thalamocortical (TC relay neurons receivingcorrelated inhibitory input from the internal segment of the globus pallidus(GPi, a primary output nucleus of the basal ganglia. We observethat the strength of correlations of TC neuron spike trains increaseswith the GPi correlation level, and bursty firing patterns such as thoseseen in the parkinsonian GPi allow for stronger transfer of correlationsthan do firing patterns found under normal conditions. We also showthat the T-current in the TC neurons does not significantly affect correlationtransfer, despite its pronounced effects on spiking. Oscillatoryfiring patterns in GPi are shown to affect the timescale at which correlationsare best transferred through the system. To explain this lastresult, we analytically compute the spike count correlation coefficientfor oscillatory cases in a reduced point process model. Our analysisindicates that the dependence of the timescale of correlation transfer isrobust to different levels of input spike and rate correlations and arisesdue to differences in instantaneous spike correlations, even when thelong timescale rhythmic modulations of neurons are identical. Overall,these results show that parkinsonian firing patterns in GPi do affectthe transfer of correlations to the thalamus.

  8. Coordinated Beating of Algal Flagella is Mediated by Basal Coupling

    Science.gov (United States)

    Wan, Kirsty; Goldstein, Raymond

    Cilia or flagella often exhibit synchronized behavior. This includes phase-locking, as seen in Chlamydomonas, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga Volvox has shown that hydrodynamic coupling alone is sufficient for synchrony. However, the situation is more complex when considering multiple flagella on a single cell. We suggest that a mechanism, internal to the cell, provides an additional flagellar coupling. For instance, flagella of Chlamydomonas mutants deficient in filamentary connections between basal bodies are found to display markedly different synchronization from the wildtype. Diverse flagellar coordination strategies found in quadri-, octo- and hexadecaflagellates reveal further evidence that intracellular couplings between flagellar basal bodies compete with hydrodynamic interactions to determine the precise form of flagellar synchronization in unicellular algae.

  9. Novelty encoding by the output neurons of the basal ganglia

    Directory of Open Access Journals (Sweden)

    Mati Joshua

    2010-01-01

    Full Text Available Reinforcement learning models of the basal ganglia have focused on the resemblance of the dopamine signal to the temporal difference error. However the role of the network as a whole is still elusive, in particular whether the output of the basal ganglia encodes only the behavior (actions or it is part of the valuation process. We trained a monkey extensively on a probabilistic conditional task with seven fractal cues predicting rewarding or aversive outcomes (familiar cues. Then in each recording session we added a cue that the monkey had never seen before (new cue and recorded from single units in the Substantia Nigra pars reticulata (SNpr while the monkey was engaged in a task with new cues intermingled within the familiar ones. The monkey learned the association between the new cue and outcome and modified its licking and blinking behavior which became similar to responses to the familiar cues with the same outcome. However, the responses of many SNpr neurons to the new cue exceeded their response to familiar cues even after behavioral learning was completed. This dissociation between behavior and neural activity suggests that the BG output code goes beyond instruction or gating of behavior to encoding of novel cues. Thus, BG output can enable learning at the levels of its target neural networks.

  10. Morphological elucidation of basal ganglia circuits contributing reward prediction

    Directory of Open Access Journals (Sweden)

    Fumino eFujiyama

    2015-02-01

    Full Text Available Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits.The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments.

  11. Mephedrone alters basal ganglia and limbic dynorphin systems.

    Science.gov (United States)

    German, Christopher L; Alburges, Mario E; Hoonakker, Amanda J; Fleckenstein, Annette E; Hanson, Glen R

    2014-08-25

    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D1 -like (SCH-23380) or D2 -like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  12. Unilateral germinomas involving the basal ganglia and thalamus.

    Science.gov (United States)

    Kobayashi, T; Kageyama, N; Kida, Y; Yoshida, J; Shibuya, N; Okamura, K

    1981-07-01

    Clinical characteristics of six cases of germinoma involving a unilateral basal ganglion and thalamus are summarized. The incidence was estimated as 10% of all intracranial germinomas. The average age at the onset was 10.5 years. The sex incidence showed a male dominance. The clinical course was slowly progressive, and the average duration between onset and diagnosis was 2 years 5 months. Common symptoms and signs were hemiparesis in all cases, fever of unknown origin and eye symptoms in most, mental deterioration and psychiatric signs in three, and convulsions, pubertas praecox, and diabetes insipidus in two. Signs of increased intracranial pressure were found in only two cases in the later state of the disease. Early diagnosis is difficult because of nonspecific symptomatology and slow progression. Carotid angiography and pneumoencephalography showed abnormal findings compatible with basal ganglia and thalamic tumors, but not specific to germinoma. Ipsilateral cortical atrophy and ventricular dilatation might be significant findings. Radioisotope scanning was useful. Computerized tomography scans were the best method of detecting the location and nature of this tumor, and repeat scans showed response to radiation therapy. PMID:7241216

  13. Familial idiopathic basal ganglia calcification (Fahr’s disease)

    Science.gov (United States)

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.

    2014-01-01

    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr’s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr’s disease. PMID:24983277

  14. Familial idiopathic basal ganglia calcification (Fahr`s disease).

    Science.gov (United States)

    Mufaddel, Amir A; Al-Hassani, Ghanem A

    2014-07-01

    Familial idiopathic basal ganglia calcification (Fahr`s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr`s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr`s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr`s disease.

  15. Clinical variants, stages, and management of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lyubomir A Dourmishev

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  16. Nucleosome distortion as a possible mechanism of transcription activation domain function.

    Science.gov (United States)

    Erkina, Tamara Y; Erkine, Alexandre M

    2016-01-01

    After more than three decades since the discovery of transcription activation domains (ADs) in gene-specific activators, the mechanism of their function remains enigmatic. The widely accepted model of direct recruitment by ADs of co-activators and basal transcriptional machinery components, however, is not always compatible with the short size yet very high degree of sequence randomness and intrinsic structural disorder of natural and synthetic ADs. In this review, we formulate the basis for an alternative and complementary model, whereby sequence randomness and intrinsic structural disorder of ADs are necessary for transient distorting interactions with promoter nucleosomes, triggering promoter nucleosome translocation and subsequently gene activation. PMID:27679670

  17. Dynamic associations of transcription factors with the rat liver nuclear matrix are functionally related to differential alpha-2-macroglobulin gene expression

    OpenAIRE

    Dinić Svetlana; Mihailović Mirjana; Ivanović-Matić Svetlana; Uskoković Aleksandra; Grdović Nevena; Vidaković Melita; Poznanović G.

    2008-01-01

    Participation of the nuclear matrix in regulation of alpha-2-macroglobulin (α2M) gene transcription during rat liver development and the acute-phase (AP) response are examined. DNA affinity chromatography of fetal and adult liver internal nuclear matrix proteins under basal and AP conditions with the α2M gene promoter (-852/+12) and immunoblot analysis revealed diverse patterns of association of transcription factors with the nuclear matrix. HNF-6, C/EBPα, and STAT5b were involved in basal an...

  18. RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Huang, Jing; Hu, Zhi

    2011-11-15

    RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.

  19. Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes.

    Science.gov (United States)

    Chymkowitch, Pierre; Nguéa, Aurélie P; Aanes, Håvard; Koehler, Christian J; Thiede, Bernd; Lorenz, Susanne; Meza-Zepeda, Leonardo A; Klungland, Arne; Enserink, Jorrit M

    2015-06-01

    Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Genome-wide expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs. PMID:25800674

  20. Three wall-associated kinases required for rice basal immunity form protein complexes in the plasma membrane.

    Science.gov (United States)

    Cayrol, Bastien; Delteil, Amandine; Gobbato, Enrico; Kroj, Thomas; Morel, Jean-Benoit

    2016-01-01

    Receptor-like kinases (RLKs) play key roles in disease resistance, in particular basal immunity. They recognize patterns produced by the pathogen invasion and often work as complexes in the plasma membrane. Among these RLKs, there is increasing evidence in several plant species of the key role of Wall-associated kinases (WAKs) in disease resistance. We recently showed using rice (Oryza sativa) loss-of-function mutants of three transcriptionally co-regulated OsWAK genes that individual OsWAKs are positively required for quantitative resistance to the rice blast fungus, Magnaporthe oryzae. This finding was unexpected since WAK genes belong to large gene families where functional redundancy is expected. Here we provide evidence that this may be due to complex physical interaction between OsWAK proteins. PMID:26853099

  1. The chromatin remodeler Mi-2beta is required for establishment of the basal epidermis and normal differentiation of its progeny.

    Science.gov (United States)

    Kashiwagi, Mariko; Morgan, Bruce A; Georgopoulos, Katia

    2007-04-01

    Using conditional gene targeting in mice, we show that the chromatin remodeler Mi-2beta is crucial for different aspects of skin development. Early (E10.5) depletion of Mi-2beta in the developing ventral epidermis results in the delayed reduction of its suprabasal layers in late embryogenesis and to the ultimate depletion of its basal layer. Later (E13.5) loss of Mi-2beta in the dorsal epidermis does not interfere with suprabasal layer differentiation or maintenance of the basal layer, but induction of hair follicles is blocked. After initiation of the follicle, some subsequent morphogenesis of the hair peg may proceed in the absence of Mi-2beta, but production of the progenitors that give rise to the inner layers of the hair follicle and hair shaft is impaired. These results suggest that the extended self-renewal capacity of epidermal precursors arises early during embryogenesis by a process that is critically dependent on Mi-2beta. Once this process is complete, Mi-2beta is apparently dispensable for the maintenance of established repopulating epidermal stem cells and for the differentiation of their progeny into interfollicular epidermis for the remainder of gestation. Mi-2beta is however essential for the reprogramming of basal cells to the follicular and, subsequently, hair matrix fates.

  2. Homeodomain transcription factor and tumor suppressor Prep1 is required to maintain genomic stability

    OpenAIRE

    Iotti, Giorgio; Longobardi, Elena; Masella, Silvia; Dardaei, Leila; De Santis, Francesca; Micali, Nicola; Blasi, Francesco

    2011-01-01

    Prep1 is a homeodomain transcription factor that is essential in embryonic development and functions in the adult as a tumor suppressor. We show here that Prep1 is involved in maintaining genomic stability and preventing neoplastic transformation. Hypomorphic homozygous Prep1i/i fetal liver cells and mouse embryonic fibroblasts (MEFs) exhibit increased basal DNA damage and normal DNA damage response after γ-irradiation compared with WT. Cytogenetic analysis shows the presence of numerous chro...

  3. Chromosome 10p deletion in a patient with hypoparathyroidism, severe mental retardation, autism and basal ganglia calcifications.

    Science.gov (United States)

    Verri, Annapia; Maraschio, Paola; Devriendt, Koen; Uggetti, Carla; Spadoni, Emanuela; Haeusler, Edward; Federico, Antonio

    2004-01-01

    Chromosome 10p terminal deletions have been associated with a DiGeorge like phenotype. Haploinsufficiency of the region 10p14-pter, results in hypoparathyroidism, sensorineural deafness, renal anomaly, that is the triad that features the HDR syndrome. Van Esch (2000) identified in a HDR patient, within a 200 kb critical region, the GATA3 gene, a transcription factor involved in the embryonic development of the parathyroids, auditory system and kidneys. We describe a new male patient, 33-year-old, with 10p partial deletion affected by hypocalcemia, basal ganglia calcifications and a severe autistic syndrome associated with mental retardation. Neurologically he presented severe impairment of language, hypotonia, clumsiness and a postural dystonic attitude. A peripheral involvement of auditory pathways was documented by auditory evoked potentials alterations. CT scan documented basal ganglia calcifications. Hyperintensity of the lentiform nuclei was evident at the MRI examination. Renal ultrasound scan was normal. Haploinsufficiency for GATA3 gene was documented with FISH analysis using cosmid clone 1.2. Phenotypic spectrum observed in del (10p) is more severe than the classical DGS spectrum. GATA3 has been found to regulate the development of serotoninergic neurons. A serotoninergic dysfunction may be linked with autism in this patient. PMID:15337474

  4. Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X.

    Directory of Open Access Journals (Sweden)

    Sebastian Haesler

    2007-12-01

    Full Text Available The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD, a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2.

  5. Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Mitrugno Valentina

    2010-11-01

    Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.

  6. Reduced brain perfusion in basal forebrain associated with cognitive decline in Alzheimer's diseases: a Tc-99m HMPAO SPECT study

    International Nuclear Information System (INIS)

    Aim: Reduction of regional cerebral blood flow (rCBF) in various cerebral regions and decline of cognitive function have been reported in Alzheimer's disease (AD) patients. The aim of this study was to identify the brain areas showing correlation between longitudinal changes of rCBFs and decline of general mental function, measured by Mini-Mental State Examination (MMSE) in probable Alzheimer's disease patients. Materials and Methods: Nine probable AD patients according to NINCDS-ADRDA criteria and DSM-IV were studied with Tc-99m HMPAO SPECT at an initial point and at the follow-up after a period of average 1.8 year. MMSE score was obtained in both occasions (average MMSE 16.4 at initial study; average MMSE = 8.1 at follow-up). Single SPECT was performed in 30 age-matched normal controls. Each SPECT image was normalized to the cerebellar activity. Using statistical parametric mapping (SPM99), correlation was analyzed between individual changes in rCBF of two SPECT scans and the MMSE scores at the time of each study in AD patients. In addition, the SPECT images of the initial study and the follow-up study were compared with SPECT images of the age-matched normal group respectively. Results: Significant correlation between longitudinal changes of rCBFs and MMSE scores was found in left basal forebrain region including substantia innominata (x, y, z = -24, 16, -23; P < .05, corrected). Within a short follow-up period of 1.8 years, cerebral hypoperfusion extended to various cortical regions from bilateral temporo-parietal to bilateral frontal regions and cingulate cortex, compared to normal controls. Conclusion: The decline of cognitive function in individual AD patients was correlated with rCBF reduction in left basal forebrain. This finding supports the cholinergic hypothesis of AD since hypoperfusion in basal forebrain region might indicate deterioration of cholinergic neurons in nucleus basalis of Meynert or substantia innominata

  7. Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A.

    Science.gov (United States)

    Kirkham, Justin K; Park, Sung Hee; Nguyen, Tu N; Lee, Ju Huck; Günzl, Arthur

    2016-01-01

    Dynein light chain LC8 is highly conserved among eukaryotes and has both dynein-dependent and dynein-independent functions. Interestingly, LC8 was identified as a subunit of the class I transcription factor A (CITFA), which is essential for transcription by RNA polymerase I (Pol I) in the parasite Trypanosoma brucei. Given that LC8 has never been identified with a basal transcription factor and that T. brucei relies on RNA Pol I for expressing the variant surface glycoprotein (VSG), the key protein in antigenic variation, we investigated the CITFA-specific role of LC8. Depletion of LC8 from mammalian-infective bloodstream trypanosomes affected cell cycle progression, reduced the abundances of rRNA and VSG mRNA, and resulted in rapid cell death. Sedimentation analysis, coimmunoprecipitation of recombinant proteins, and bioinformatic analysis revealed an LC8 binding site near the N terminus of the subunit CITFA2. Mutation of this site prevented the formation of a CITFA2-LC8 heterotetramer and, in vivo, was lethal, affecting assembly of a functional CITFA complex. Gel shift assays and UV cross-linking experiments identified CITFA2 as a promoter-binding CITFA subunit. Accordingly, silencing of LC8 or CITFA2 resulted in a loss of CITFA from RNA Pol I promoters. Hence, we discovered an LC8 interaction that, unprecedentedly, has a basal function in transcription.

  8. Pax258 and Pax6 alternative splicing events in basal chordates and vertebrates: a focus on paired box domain

    Directory of Open Access Journals (Sweden)

    Peter eFabian

    2015-07-01

    Full Text Available Paired box transcription factors play important role in development and tissue morphogenesis. The number of Pax homologs varies among species studied so far, due to genome and gene duplications that have affected PAX family to a great extent. Based on sequence similarity and functional domains, four Pax classes have been identified in chordates, namely Pax1/9, Pax2/5/8, Pax3/7 and Pax4/6. Numerous splicing events have been reported mainly for Pax2/5/8 and Pax6 genes. Of significant interest are those events that lead to Pax proteins with presumed novel properties, such as altered DNA-binding or transcriptional activity. In the current study, a thorough analysis of Pax2/5/8 splicing events from cephalochordate and vertebrates was performed. We focused more on Pax2/5/8 and Pax6 splicing events in which the paired domain is involved. Three new splicing events were identified in Oryzias latipes, one of which seems to be conserved in Acanthomorphata. Using representatives from deuterostome and protostome phyla, a comparative analysis of the Pax6 exon-intron structure of the paired domain was performed, during an attempt to estimate the time of appearance of the Pax6(5a mRNA isoform. As shown in our analysis, this splicing event is absent in basal chordates and is characteristic of Gnathostomata. Moreover, expression pattern of alternative spliced variants was compared between basal chordates and fish species. In summary, our data indicate expansion of alternative mRNA variants in paired box region of Pax2/5/8 and Pax6 genes during the course of vertebrate evolution.

  9. Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and response to released ATP.

    Science.gov (United States)

    Ostrom, R S; Gregorian, C; Drenan, R M; Gabot, K; Rana, B K; Insel, P A

    2001-08-01

    Madin-Darby canine kidney (MDCK) cells release ATP upon mechanical or biochemical activation, initiating P2Y receptor signaling that regulates basal levels of multiple second messengers, including cAMP (J Biol Chem 275: 11735--11739, 2000). Data shown here document inhibition of cAMP formation by Gd(3+) and niflumic acid, channel inhibitors that block ATP release. cAMP production is stimulated via Ca(2+)-dependent activation of cytosolic phospholipase A(2), release of arachidonic acid (AA), and cyclooxygenase (COX)-dependent production of prostaglandins, which activate prostanoid receptors coupled to G(s) and adenylyl cyclase. In the current investigation, we assessed the expression and functional role of the two known isoforms of COX, COX-1 and COX-2. Treatment of cells with either a COX-1-selective inhibitor, SC-560, or COX-2-selective inhibitors, SC-58125 or NS-398, inhibited basal and UTP-stimulated cAMP levels. COX inhibitors also decreased forskolin-stimulated cAMP formation, implying this response is in part attributable to an action of AA metabolites. These findings imply an important role for the inducible form of COX, COX-2, under basal conditions. Indeed, COX-2 expression was readily detectable by immunoblot, and treatments that induce or reduce COX-2 expression in other cells (interleukin-1beta, tumor necrosis factor-alpha, phorbol ester, or dexamethasone) had minimal or no effect on the levels of COX-2 immunoreactivity. RT-PCR using isoform-specific primers detected COX-2 mRNA. We conclude that COX-2 is constitutively expressed in MDCK-D(1) cells and participates in basal and P2Y(2)-mediated signaling, implying a key role for COX-2 in regulation of epithelial cell function. PMID:11443051

  10. The Arabidopsis DREB2 genetic pathway is constitutively repressed by basal phosphoinositide-dependent phospholipase C coupled to diacylglycerol kinase in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Nabila eDjafi

    2013-08-01

    Full Text Available Phosphoinositide-dependent phospholipases C (PI-PLCs are activated in response to various stimuli. They utilize substrates provided by type III-Phosphatidylinositol-4 kinases (PI4KIII to produce inositol triphosphate and diacylglycerol (DAG that is phosphorylated into phosphatidic acid (PA by DAG-kinases (DGKs. The roles of PI4KIIIs, PI-PLCs and DGKs in basal signalling are poorly understood. We investigated the control of gene expression by basal PI-PLC pathway in Arabidopsis thaliana suspension cells. A transcriptome-wide analysis allowed the identification of genes whose expression was altered by edelfosine, 30 µM wortmannin or R59022, inhibitors of PI-PLCs, PI4KIIIs and DGKs, respectively. We found that a gene responsive to one of these molecules is more likely to be similarly regulated by the other two inhibitors. The common action of these agents is to inhibit PA formation, showing that basal PI-PLCs act, in part, on gene expression through their coupling to DGKs. Amongst the genes up-regulated in presence of the inhibitors, were some DREB2 genes, in suspension cells and in seedlings. The DREB2 genes encode transcription factors with major roles in responses to environmental stresses, including dehydration. They bind to C-repeat motifs, known as Drought-Responsive Elements, that are indeed enriched in the promoters of genes up-regulated by PI-PLC pathway inhibitors. PA can also be produced by phospholipases D (PLDs. We show that the DREB2 genes that are up-regulated by PI-PLC inhibitors are positively or negatively regulated, or indifferent, to PLD basal activity. Our data show that the DREB2 genetic pathway is constitutively repressed in resting conditions and that DGK coupled to PI-PLC is active in this process, in suspension cells and seedlings. We discuss how this basal negative regulation of DREB2 genes is compatible with their stress-triggered positive regulation.

  11. [Structure of the mushroom-like bodies in lamellar-antennae beetles (Coleoptera: Scarabaeoidea). 1. Basal families and coprophagy Scarabaeoidea].

    Science.gov (United States)

    Panov, A A

    2010-01-01

    Mushroom bodies are in general similarly developed in most taxons studied. The calyx region appears as a single structure, and its dual nature is not yet realized. An anterio-posterior asymmetry of the calyx region with Kenyon cell processes running mostly behind the glomerular neuropil of the calyx is characteristic of all the species studied. In this respect, the calyx region of basal Scarabaeoidea resembles greatly the calyx of many dipterans. Lobe compartmentalization occurs at the initial stage. The passalid beetles represent an exception, as their mushroom bodies are much more developed than in related families. This may be connected with the complicated social behavior of Passalidae.

  12. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

  13. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    . Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

  14. Spatial Variation of Basal Conditions on Kamb Ice Stream

    Science.gov (United States)

    Jacobel, R. W.; Welch, B. C.; Osterhouse, D.; Pettersson, R.; MacGregor, J. A.

    2007-12-01

    Radar profiles of bed echo intensity provide a way to survey conditions at the ice-bed interface and test for the presence or absence of water. However, extracting information about bed properties from bed echo intensities requires an estimate of the dielectric attenuation loss through the ice. A recent survey [MacGregor et al., 2007] found that the few reported values of depth-averaged attenuation rates in West Antarctica vary by a factor of 3, presumably due to spatial variations in the chemistry and temperature profiles of the ice. Thus, a single value for depth-averaged ice-sheet attenuation cannot be assumed, even over a relatively small region. We measured attenuation rates at several locations on and near Kamb Ice Stream (KIS) by examining basal echo intensity values as a function of ice thickness from constant-offset radar data acquired in 2004-2006. Our values obtained for Siple Dome of 29 dB/km agree with previous measurements [Gades et al., 2000] and the recent calculations and model results of MacGregor et al. [2007]. On KIS, we measured attenuation values of 20 dB/km over the "sticky spot", where ice has become stagnant. This value is consistent with an attenuation model over the sticky spot calculated using borehole temperature data [Engelhardt, 2005] and chemistry data from the Siple Dome ice core. Our radar profiles in the main trunk region of KIS yield a slightly lower value of 15 dB/km, presumably because colder ice is still being advected from inland West Antarctica. Using these values of attenuation, we calculated the basal radar reflectivity at the ice-bed interface in the regions of all our surveys. We found that most regions of the bed in the trunk of KIS have high basal reflectivities and that these values are similar to those obtained in locations where water was found in the Caltech boreholes [Engelhardt, 2005]. Areas of lower bed reflectivity are limited to the sticky spot, where a borehole found a dry bed, and along the margins of KIS

  15. Submillisecond precision of the input-output transformation function mediated by fast sodium dendritic spikes in basal dendrites of CA1 pyramidal neurons.

    Science.gov (United States)

    Ariav, Gal; Polsky, Alon; Schiller, Jackie

    2003-08-27

    The ability of cortical neurons to perform temporally accurate computations has been shown to be important for encoding of information in the cortex; however, cortical neurons are expected to be imprecise temporal encoders because of the stochastic nature of synaptic transmission and ion channel gating, dendritic filtering, and background synaptic noise. Here we show for the first time that fast local spikes in basal dendrites can serve to improve the temporal precision of neuronal output. Integration of coactivated, spatially distributed synaptic inputs produces temporally imprecise output action potentials within a time window of several milliseconds. In contrast, integration of closely spaced basal inputs initiates local dendritic spikes that amplify and sharpen the summed somatic potential. In turn, these fast basal spikes allow precise timing of output action potentials with submillisecond temporal jitter over a wide range of activation intensities and background synaptic noise. Our findings indicate that fast spikes initiated in individual basal dendrites can serve as precise "timers" of output action potentials in various network activity states and thus may contribute to temporal coding in the cortex.

  16. Selective Vulnerability of the Cochlear Basal Turn to Acrylonitrile and Noise

    Directory of Open Access Journals (Sweden)

    B. Pouyatos

    2009-01-01

    Full Text Available Exposure to acrylonitrile, a high-production industrial chemical, can promote noise-induced hearing loss (NIHL in the rat even though this agent does not itself produce permanent hearing loss. The mechanism by which acrylonitrile promotes NIHL includes oxidative stress as antioxidant drugs can partially protect the cochlea from acrylonitrile+noise. Acrylonitrile depletes glutathione levels while noise can increase the formation of reactive oxygen species. It was previously noted that the high-frequency or basal turn of the cochlea was particularly vulnerable to the combined effects of acrylonitrile and noise when the octave band noise (OBN was centered at 8 kHz. Normally, such a noise would be expected to yield damage at a more apical region of the cochlea. The present study was designed to determine whether the basal cochlea is selectively sensitive to acrylonitrile or whether, by adjusting the frequency of the noise band, it would be possible to control the region of the auditory impairment. Rats were exposed to one of three different OBNs centered at different frequencies (4 kHz, 110 dB and 8 or 16 kHz at 97 dB for 5 days, with and without administration of acrylonitrile (50 mg/kg/day. The noise was set to cause limited NIHL by itself. Auditory function was monitored by recording distortion products, by compound action potentials, and by performing cochlear histology. While the ACN-only and noise-only exposures induced no or little permanent auditory loss, the three exposures to acrylonitrile+noise produced similar auditory and cochlear impairments above 16 kHz, despite the fact that the noise exposures covered 2 octaves. These observations show that the basal cochlea is much more sensitive to acrylonitrile+noise than the apical partition. They provide an initial basis for distinguishing the pattern of cochlear injury that results from noise exposure from that which occurs due to the combined effects of noise and a chemical

  17. TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

    KAUST Repository

    Schaefer, Ulf

    2010-10-21

    The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

  18. Optimization of competitively differentiated polymerase chain reaction in detection of HBV basal core promoter mutation

    Institute of Scientific and Technical Information of China (English)

    Xiao-Mou Peng; Lin Gu; Xue-Juan Chen; Jian-Guo Li; Yang-Su Huang; Zhi-Liang Gao

    2005-01-01

    AIM: To improve competitively differentiated polymerase chain reaction (CD-PCR) in detection of HBV basal core promoter mutation.METHODS: Recombinant plasmid of double point mutation A1762T/G1764A in basal core promoter of HBV constructed by site-directed mutagenesis was used as mutant control.To reveal the deficiency mechanism of CD-PCR, relationship between the circle number of PCR and the increased speed of products of each competitive primer was comparatively studied. Diversified amount of dNTPs and mutual primer of the competitive primers were tried to optimize CDPCR. Optimized CD-PCR was evaluated by detecting A1762T/G1764A mutation in recombinant plasmids and clinical sera from patients with HBV infection. RESULTS: The deficiency mechanism of CD-PCR was that the products of mismatched competitive primer grew fast when the amplification of matched primer entered into plateau stage, which led to decrease in or disappearance of the difference in the amount of their products. This phenomenon could be eliminated by reducing dNTPs to10 μmol/L and mutual primer to about 100 nmol/L. Optimized CD-PCR could detect both mutant and wild strain indepe ndent of the amount of templates and the number of PCRcycles. Its detection limit was 103 copies/mL, about 50 copies/reaction. About 10% of mutant DNAs among wild type DNAs could be detected. A1762T/G1764A mutant was detected in 41.8% (51/122) of patients with HBV infection, but not detected in controls with negative HBsAg. CONCLUSION: Optimized CD-PCR can detect mutation independent of the amount of initial templates and the number of PCR cycles.

  19. Desalination of Basal Water by Mesoporous Carbons Nanocomposite Membrane.

    Science.gov (United States)

    Choi, Jeongdong; Ahn, Youngho; Gamal El-Din, Mohamed; Kim, Eun-Sik

    2016-02-01

    The hydro-transportation process used to obtain bitumen from the Alberta oil sands produces large volume of basal depressurization water (BDW), which contains high salt concentrations. In this research, thin-film nanocomposite (TFN) membrane technology applied to treat BDW in lab-scale, and evaluated water properties before and after the treatment. The average rejection ratios of ionic species were 95.2% and 92.8% by TFN membrane (with ordered mesoporous carbons (OMCs)) and thin-film composite (TFC) (without OMCs) membrane, respectively. The turbidity and total dissolved solids (TDS) were completely rejected in all treatment conditions. Interestingly, the water flux of TFN membrane was dramatically increased compared to TFC membrane. The increase of water flux was believed to be caused by the increased membrane surface hydrophilicity and nano-pore effects by the OMCs.

  20. A basal tyrannosauroid dinosaur from the Late Jurassic of China.

    Science.gov (United States)

    Xu, Xing; Clark, James M; Forster, Catherine A; Norell, Mark A; Erickson, Gregory M; Eberth, David A; Jia, Chengkai; Zhao, Qi

    2006-02-01

    The tyrannosauroid fossil record is mainly restricted to Cretaceous sediments of Laurasia, although some very fragmentary Jurassic specimens have been referred to this group. Here we report a new basal tyrannosauroid, Guanlong wucaii gen. et sp. nov., from the lower Upper Jurassic of the Junggar Basin, northwestern China. G. wucaii is the oldest known tyrannosauroid and shows several unexpectedly primitive pelvic features. Nevertheless, the limbs of G. wucaii share several features with derived coelurosaurs, and it possesses features shared by other coelurosaurian clades. This unusual combination of character states provides an insight into the poorly known early radiation of the Coelurosauria. Notably, the presumed predatory Guanlong has a large, fragile and highly pneumatic cranial crest that is among the most elaborate known in any non-avian dinosaur and could be comparable to some classical exaggerated ornamental traits among vertebrates.