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Carsten Schurmann - One of the best experts on this subject based on the ideXlab platform.

  • cElf a logical framework for deductive and concurrent systems system description
    International Joint Conference on Automated Reasoning, 2008
    Co-Authors: Anders Schacknielsen, Carsten Schurmann
    Abstract:

    CLF (Concurrent LF) [CPWW02a] is a logical framework for specifying and implementing deductive and concurrent systems from areas, such as programming language theory, security protocol analysis, process algebras, and logics. CElf is an implementation of the CLF type theory that extends the LF type theory by linear types to support representation of state and a monad to support representation of concurrency. It relies on the judgments-as-types methodology for specification and the interpretation of CLF signatures as concurrent logic programs [LPPW05] for experimentation. CElf is written in Standard ML and compiles with MLton, MLKit, and SML/NJ. The source code and a collection of examples are available from http://www.twElf.org/~cElf .

Wilma Jogunoori - One of the best experts on this subject based on the ideXlab platform.

  • Aberrant Wnt/β-catenin signaling in TGF-β pathway Elf+/-, and Elf+/-/smad3+/- mutant mouse models of human Beckwith- Wiedemann Syndrome
    Cancer Research, 2008
    Co-Authors: Geeta Upadhyay, Rupin Amin, Wilma Jogunoori, Stephen Evans, Bibhuti Mishra, E. P. Reddy, Lopa Mishra
    Abstract:

    3457 Background:
 We have shown that adaptor protein Elf, a β-spectrin is a key mediator of TGF-β signaling (Science, 2003 Jan 24; 299). Disruption of TGF-β signaling through Elf and SMAD4 leads to gastrointestinal tumors with aberrant E-Cadherin and β-catenin interaction (Science, 2005, Oct 7; 310, Oncogene, 2006 Mar 23; 25). Interestingly, heterozygous deletion of Elf+/-and smad3+/- leads to spontaneous multi-organ tumor growth with a compelling phenotype of human Beckwith-Wiedemann syndrome (BWS). Elf and Elf+/-/smad3+/- mutant mice develop a high frequency of tumors in organs of endodermal lineage including liver, pancreas, stomach, small intestine, lung, thymus, and, kidney. This mouse model provides an excellent opportunity to study the tumorigenecity due to disruptions in the TGF-β pathway as well as provide insight into human BWS, a human hereditary cancer syndrome. The Beckwith-Wiedemann syndrome (BWS) has no clear causal mutation, with loss of imprinting at chromosome 11 and amplification of insulin-like growth factor 2 (IGF2), which is also increased (10-20% of cases) in Elf+/-and Elf+/-/smad3+/- mouse model of BWS.
 Aims
 1. Identify oncogenic pathways that are activated in the Elf+/-and Elf+/-/smad3+/- tumors
 2. Study the molecular mechanism by which loss of TGF-β signaling leads to tumorigenesis in this mouse model of BWS.
 Methods and Results:
 1. Broad micro array analysis revealed a marked increase in gene expression in the Wnt pathway i.e. Wnt11/16, Frizzled4/5 and LRP6.
 2. Endogenous Elf interacts with β-catenin which is in the center of Wnt signaling. Elf is also required for localization of β-catenin associated molecule E-cadherin at the adherence junctions.
 3. Tumors from Elf+/- and Elf+/-/smad3+/- mice show a marked abnormal accumulation of nuclear β-catenin and its target gene c-Myc at RNA and protein levels.
 4. Tumors from Elf+/- and Elf+/-/smad3+/- mice also show 10 fold higher protein expression of IGF2 protein. Transcript levels of one of the IGF2 regulators, HIFα is also increased as seen by micro array analysis.
 Conclusions:
 1. Wnt/β-catenin pathway is activated in these mouse models of BWS, and potentially provides a strong therapeutic target in BWS tumors. In human BWS elevated levels of β-catenin has been reported (Pediatr Dev Pathol, 2003 Jul-Aug; 6)
 2. Elf could regulate Wnt signaling most likely by direct interaction with β-catenin.
 3. Regulation of Wnt/β-catenin signaling by Elf could be mediated by high IGF2. IGF2 has been shown to increase Frizzled mediated Wnt/β-catenin signaling (4). IGF2 is associated with human BWS. The mechanism of IGF2 regulation by Elf is under investigation.
 4. Elf+/-and Elf+/-/smad3+/- mice present as powerful models for analyzing the pathophysiology of BWS and generating new therapeutics for these cancers.

  • disruption of transforming growth factor β signaling through β spectrin Elf leads to hepatocellular cancer through cyclin d1 activation
    Oncogene, 2007
    Co-Authors: Krit Kitisin, Wilma Jogunoori, Varalakshmi Katuri, Yi Tang, Eugene A. Volpe, Natarajan Ganesan, Sang Kim, Bhaskar Kallakury, Michael J Pishvaian, Christopher Albanese
    Abstract:

    Transforming growth factor-beta (TGF-beta) signaling members, TGF-beta receptor type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (Elf), are prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40% of Elf(+/-) mice spontaneously develop hepatocellular cancer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression. Reduced Elf but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (P<0.017). Elf and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU-475. Restoration of Elf and TBRII in SNU-398 cells markedly decreases cyclin D1 as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we show that TGF-beta signaling and Smad adaptor Elf suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of Elf could serve as a primary event in progression toward a fully transformed phenotype and could hold promise for new therapeutic approaches in human HCCs.

  • Inactivation of Elf/TGF-β signaling in human gastrointestinal cancer
    Oncogene, 2005
    Co-Authors: Varalakshmi Katuri, Wilma Jogunoori, Yi Tang, Blair Marshall, Asif Rashid, Eugene A. Volpe, Anton N. Sidawy, Stephen R.t. Evans, Jonathan Blay, G. Ian Gallicano
    Abstract:

    TGF-β/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Elf, a β-spectrin, plays a key role in the transmission of TGF-β-mediated transcriptional response through Smads. Elf was originally identified as a key protein involved in endodermal stem/progenitor cells committed to foregut lineage. Also, as a major dynamic adaptor and scaffolding protein, Elf is important for the generation of functionally distinct membranes, protein sorting and the development of polarized differentiated epithelial cells. Disruption of Elf results in the loss of Smad3/Smad4 activation and, therefore, a disruption of the TGF-β pathway. These observations led us to pursue the function of Elf in gastrointestinal (GI) epithelial cell–cell adhesion and tumor suppression. Here, we show a significant loss of Elf and reduced Smad4 expression in human gastric cancer tissue samples. Also, of the six human gastric cancer cell lines examined, three show deficient Elf expression. Furthermore, we demonstrate the rescue of E-cadherin-dependent homophilic cell–cell adhesion by ectopic expression of full-length Elf. Our results suggest that Elf has an essential role in tumor suppression in GI cancers.

Jean Galy - One of the best experts on this subject based on the ideXlab platform.

  • Stereochemistry and ab initio topology analyses of electron lone pair triplets and twins in interhalogen compounds and halogen suboxides
    Progress in Solid State Chemistry, 2017
    Co-Authors: Samir Matar, Guillaume Couégnat, Jean Galy
    Abstract:

    The paper reports a thorough investigation of little inspected two classes of group VIIA based crystals: interhalogen compounds ClF, ClF3, BrF3 and IF3 on one hand and halogen suboxides F2O, Cl2O and Br2O on the other hand, as well as rare gas fluorides (here exemplarily XeF4), all exhibiting peculiar stereochemistry of electron (non-bonding) lone pairs merging in forms of twins and triplets. Particularly with respect to the well known VSEPR (Valence Shell Electron Pair Repulsion) model we present original approach merging crystal chemistry and density functional theory (DFT) electron localization function (Elf) to provide accurate topologic analyses and precise metrics of electron lone pairs geometries. In this context we rewrite the chemical formulae above by adjoining E designing the lone pair (LP) and M* formulating the LP-bearing element: ClF{E3}, M*2OE2{E3}2 (M* = F, Cl, Br), M*F3E2 (M* = Cl, Br, I) and XeF4E2. Then in ClF{E3} and M*2OE2{E3}2 (M* = F, Cl, Br) family an original stereochemistry is developed with LP concentration in E triplets which generate electronic torus revolving around Cl and M* which in the neighborhood of largely electronegative F, exhibit cationic-like behavior. E around Cl in ClF and then around M* of the series under consideration exhibits an ellipsoidic shape with an equivalent sphere of influence radius (rE) increasing along with the atomic number Z, i.e. rE_F = 0.52 Å, rE_Cl = 0.65 Å and rE_Br = 0.70 Å. From selected sections in Elf data we obtained precise topology and metrics details of these tori. For M*2OE2{E3}2 family the E twins attached to O have also been localized, their size remaining constant with rE_O = 0.68 Å in all studied compounds. The lone pair twins in the series M*F3E2 (M* = Cl, Br, I; M* trivalent oxidation state) as well as in noble gas tetrafluoride XeF4E2 provide remarkable examples: rE evolution versus Z, rE_Cl = 0.77 Å (Z = 17), rE_Br = 0.85 Å (Z = Br) and rE_I = 0.90 Å (Z = 53), follow a linear expansion while in the xenon case with a close ZXe = 54 but with tetravalent oxidation state, Xe exhibits a radius rE_Xe = 0.95 Å, indicating the important influence of the charge magnitude on E volume. The interaction of cations with E centroïd: Ec -defined as the electronic volume attached to the lone pair- of neighboring molecules is plausible in explaining unusually short distances between cations. Even surrounded by E torus the cations obviously exert attractive influence through its vortex axis.

I.s. Bright Singh - One of the best experts on this subject based on the ideXlab platform.

  • Anti-lipopolysaccharide factor and crustin-III, the anti-white spot virus peptides in Penaeus monodon: Control of viral infection by up-regulation
    Aquaculture, 2011
    Co-Authors: Swapna P. Antony, Rosamma Philip, Valsamma Joseph, I.s. Bright Singh
    Abstract:

    Abstract White Spot Syndrome Virus (WSSV) is the most devastating disease affecting shrimp culture around the world. Though, considerable progress has been made in the detection and molecular characterization of WSSV in recent years, information pertaining to immune gene expression in shrimps with respect to WSSV infection remains limited. In this context, the present study was undertaken to understand the differential expression of antimicrobial peptide (AMP) genes in the haemocytes of Penaeus monodon in response to WSSV infection on a time-course basis employing semi-quantitative RT-PCR. The present work analyzes the expression profile of six AMP genes (ALF, crustin-1, crustin-2, crustin-3, penaeidin-3 and penaeidin-5), eight WSSV genes (DNA polymerase, endonuclease, immediate early gene, latency related gene, protein kinase, ribonucleotide reductase, thymidine kinase and VP28) and three control genes (18S rRNA, β-actin and Elf) in P. monodon in response to WSSV challenge. Penaeidins were found to be up-regulated during early hours of infection and crustin-3 during late period of infection. However, ALF was found to be up-regulated early to late period of WSSV infection. The present study suggests that AMPs viz. ALF and crustin-3 play an important role in antiviral defense in shrimps. WSSV gene transcripts were detected post-challenge day 1 itsElf and increased considerably day 5 onwards. Evaluation of the control genes confirmed Elf as the most reliable control gene followed by 18S rRNA and β-actin for gene expression studies in shrimps. This study indicated the role of AMPs in the protection of shrimps against viral infection and their possible control through the up-regulation of AMPs.

Varalakshmi Katuri - One of the best experts on this subject based on the ideXlab platform.

  • disruption of transforming growth factor β signaling through β spectrin Elf leads to hepatocellular cancer through cyclin d1 activation
    Oncogene, 2007
    Co-Authors: Krit Kitisin, Wilma Jogunoori, Varalakshmi Katuri, Yi Tang, Eugene A. Volpe, Natarajan Ganesan, Sang Kim, Bhaskar Kallakury, Michael J Pishvaian, Christopher Albanese
    Abstract:

    Transforming growth factor-beta (TGF-beta) signaling members, TGF-beta receptor type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (Elf), are prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40% of Elf(+/-) mice spontaneously develop hepatocellular cancer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression. Reduced Elf but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (P<0.017). Elf and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU-475. Restoration of Elf and TBRII in SNU-398 cells markedly decreases cyclin D1 as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we show that TGF-beta signaling and Smad adaptor Elf suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of Elf could serve as a primary event in progression toward a fully transformed phenotype and could hold promise for new therapeutic approaches in human HCCs.

  • Inactivation of Elf/TGF-β signaling in human gastrointestinal cancer
    Oncogene, 2005
    Co-Authors: Varalakshmi Katuri, Wilma Jogunoori, Yi Tang, Blair Marshall, Asif Rashid, Eugene A. Volpe, Anton N. Sidawy, Stephen R.t. Evans, Jonathan Blay, G. Ian Gallicano
    Abstract:

    TGF-β/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Elf, a β-spectrin, plays a key role in the transmission of TGF-β-mediated transcriptional response through Smads. Elf was originally identified as a key protein involved in endodermal stem/progenitor cells committed to foregut lineage. Also, as a major dynamic adaptor and scaffolding protein, Elf is important for the generation of functionally distinct membranes, protein sorting and the development of polarized differentiated epithelial cells. Disruption of Elf results in the loss of Smad3/Smad4 activation and, therefore, a disruption of the TGF-β pathway. These observations led us to pursue the function of Elf in gastrointestinal (GI) epithelial cell–cell adhesion and tumor suppression. Here, we show a significant loss of Elf and reduced Smad4 expression in human gastric cancer tissue samples. Also, of the six human gastric cancer cell lines examined, three show deficient Elf expression. Furthermore, we demonstrate the rescue of E-cadherin-dependent homophilic cell–cell adhesion by ectopic expression of full-length Elf. Our results suggest that Elf has an essential role in tumor suppression in GI cancers.