Distinct Involvement of the Gab1 and Grb2 Adaptor Proteins in Signal Transduction by the Related Receptor Tyrosine Kinases RON and MET

PubMed Central

Chaudhuri, Amitabha; Xie, Ming-Hong; Yang, Becky; Mahapatra, Kaushiki; Liu, Jinfeng; Marsters, Scot; Bodepudi, Sweta; Ashkenazi, Avi

2011-01-01

Although the signal transduction mechanisms of the receptor tyrosine kinase MET are well defined, less is known about its close relative RON. MET initiates intracellular signaling by autophosphorylation on specific cytoplasmic tyrosines that form docking sites for the adaptor proteins Grb2 and Gab1. Grb2 binds directly and is essential for all of the biological activities of MET. Gab1 docks either directly or indirectly via Grb2 and controls only a subset of MET functions. Because MET and RON possess similar adaptor binding sites, it was anticipated that their adaptor interactions would be conserved. Here we show that in contrast to MET, RON relies primarily on Gab1 for signal transmission. Surprisingly, disruption of the Grb2 docking site of RON or Grb2 depletion augments activity, whereas enhancement of Grb2 binding attenuates Gab1 recruitment and signaling. Hence, RON and MET differ in their adaptor interactions; furthermore, Grb2 performs a novel antagonistic role in the context of RON signaling. PMID:21784853

Grb2 regulates B-cell maturation, B-cell memory responses and inhibits B-cell Ca2+ signalling.

PubMed

Ackermann, Jochen A; Radtke, Daniel; Maurberger, Anna; Winkler, Thomas H; Nitschke, Lars

2011-04-20

Grb2 is a ubiquitously expressed adaptor protein, which activates Ras and MAP kinases in growth factor receptor signalling, while in B-cell receptor (BCR) signalling this role is controversial. In B cell lines it was shown that Grb2 can inhibit BCR-induced Ca(2+) signalling. Nonetheless, the physiological role of Grb2 in primary B cells is still unknown. We generated a B-cell-specific Grb2-deficient mouse line, which had a severe reduction of mature follicular B cells in the periphery due to a differentiation block and decreased B-cell survival. Moreover, we found several changes in important signalling pathways: enhanced BCR-induced Ca(2+) signalling, alterations in mitogen-activated protein kinase activation patterns and strongly impaired Akt activation, the latter pointing towards a defect in PI3K signalling. Interestingly, B-cell-specific Grb2-deficient mice showed impaired IgG and B-cell memory responses, and impaired germinal centre formation. Thus, Grb2-dependent signalling pathways are crucial for lymphocyte differentiation processes, as well as for control of secondary humoral immune responses.

Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

PubMed

Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

1994-01-01

Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

Amyloid precursor protein and Presenilin1 interact with the adaptor GRB2 and modulate ERK 1,2 signaling.

PubMed

Nizzari, Mario; Venezia, Valentina; Repetto, Emanuela; Caorsi, Valentina; Magrassi, Raffaella; Gagliani, Maria Cristina; Carlo, Pia; Florio, Tullio; Schettini, Gennaro; Tacchetti, Carlo; Russo, Tommaso; Diaspro, Alberto; Russo, Claudio

2007-05-04

The amyloid precursor protein (APP) and the presenilins 1 and 2 are genetically linked to the development of familial Alzheimer disease. APP is a single-pass transmembrane protein and precursor of fibrillar and toxic amyloid-beta peptides, which are considered responsible for Alzheimer disease neurodegeneration. Presenilins are multipass membrane proteins, involved in the enzymatic cleavage of APP and other signaling receptors and transducers. The role of APP and presenilins in Alzheimer disease development seems to be related to the formation of amyloid-beta peptides; however, their physiological function, reciprocal interaction, and molecular mechanisms leading to neurodegeneration are unclear. APP and presenilins are also involved in multiple interactions with intracellular proteins, the significance of which is under investigation. Among the different APP-interacting proteins, we focused our interest on the GRB2 adaptor protein, which connects cell surface receptors to intracellular signaling pathways. In this study we provide evidence by co-immunoprecipitation experiments, confocal and electron microscopy, and by fluorescence resonance energy transfer experiments that both APP and presenilin1 interact with GRB2 in vesicular structures at the centrosome of the cell. The final target for these interactions is ERK1,2, which is activated in mitotic centrosomes in a PS1- and APP-dependent manner. These data suggest that both APP and presenilin1 can be part of a common signaling pathway that regulates ERK1,2 and the cell cycle.

HIV-1 Tat binds to SH3 domains: cellular and viral outcome of Tat/Grb2 interaction

PubMed Central

Rom, Slava; Pacifici, Marco; Passiatore, Giovanni; Aprea, Susanna; Waligorska, Agnieszka; Valle, Luis Del; Peruzzi, Francesca

2011-01-01

The Src-homology 3 (SH3) domain is one of the most frequent protein recognition modules (PRMs), being represented in signal transduction pathways and in several pathologies such as cancer and AIDS. Grb2 (growth factor receptor-bound protein 2) is an adaptor protein that contains two SH3 domains and is involved in receptor tyrosine kinase (RTK) signal transduction pathways. The HIV-1 transactivator factor Tat is required for viral replication and it has been shown to bind directly or indirectly to several host proteins, deregulating their functions. In this study, we show interaction between the cellular factor Grb2 and the HIV-1 trans-activating protein Tat. The binding is mediated by the proline-rich sequence of Tat and the SH3 domain of Grb2. As the adaptor protein Grb2 participates in a wide variety of signaling pathways, we characterized at least one of the possible downstream effects of the Tat/Grb2 interaction on the well-known IGF-1R/Raf/MAPK cascade. We show that the binding of Tat to Grb2 impairs activation of the Raf/MAPK pathway, while potentiating the PKA/Raf inhibitory pathway. The Tat/Grb2 interaction affects also viral function by inhibiting the Tat-mediated transactivation of HIV-1 LTR and viral replication in infected primary microglia. PMID:21745501

THE UNCOVERING OF A NOVEL REGULATORY MECHANISM FOR PLD2: FORMATION OF A TERNARY COMPLEX WITH PROTEIN TYROSINE PHOSPHATASE PTP1B AND GROWTH FACTOR RECEPTOR-BOUND PROTEIN GRB2

PubMed Central

Horn, Jeff; Lopez, Isabel; Miller, Mill; Gomez-Cambronero, Julian

2011-01-01

The regulation of PLD2 activation is poorly understood at present. Transient transfection of COS-7 with a mycPLD2 construct results in elevated levels of PLD2 enzymatic activity and tyrosyl phosphorylation. To investigate whether this phosphorylation affects PLD2 enzymatic activity, anti-myc immunoprecipitates were treated with recombinant protein tyrosine phosphatase PTP1B. Surprisingly, lipase activity and PY levels both increased over a range of PTP1B concentrations. These increases occurred in parallel to a measurable PTP1B-associated phosphatase activity. Inhibitor studies demonstrated that an EGF-receptor type kinase is involved in phosphorylation. In a COS-7 cell line created in the laboratory that stably expressed myc-PLD2, PTP1B induced a robust (>6-fold) augmentation of myc-PLD2 phosphotyrosine content. The addition of growth factor receptor-bound protein 2 (Grb2) to cell extracts also elevated PY levels of myc-PLD (>10-fold). Systematic co-immunoprecipitation-immunoblotting experiments pointed at a physical association between PLD2, Grb2 and PTP1B in both physiological conditions and in overexpressed cells. This is the first report of a demonstration of the mammalian isoform PLD2 existing in a ternary complex with a protein tyrosine phosphatase, PTP1b, and the docking protein Grb2 which greatly enhances tyrosyl phosphorylation of the lipase. PMID:15896299

Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action.

PubMed

Deng, Youping; Bhattacharya, Sujoy; Swamy, O Rama; Tandon, Ruchi; Wang, Yong; Janda, Robert; Riedel, Heimo

2003-10-10

The regulation of the metabolic insulin response by mouse growth factor receptor-binding protein 10 (Grb10) has been addressed in this report. We find mouse Grb10 to be a critical component of the insulin receptor (IR) signaling complex that provides a functional link between IR and p85 phosphatidylinositol (PI) 3-kinase and regulates PI 3-kinase activity. This regulatory mechanism parallels the established link between IR and p85 via insulin receptor substrate (IRS) proteins. A direct association was demonstrated between Grb10 and p85 but was not observed between Grb10 and IRS proteins. In addition, no effect of mouse Grb10 was observed on the association between IRS-1 and p85, on IRS-1-associated PI 3-kinase activity, or on insulin-mediated activation of IR or IRS proteins. A critical role of mouse Grb10 was observed in the regulation of PI 3-kinase activity and the resulting metabolic insulin response. Dominant-negative Grb10 domains, in particular the SH2 domain, eliminated the metabolic response to insulin in differentiated 3T3-L1 adipocytes. This was consistently observed for glycogen synthesis, glucose and amino acid transport, and lipogenesis. In parallel, the same metabolic responses were substantially elevated by increased levels of Grb10. A similar role of Grb10 was confirmed in mouse L6 cells. In addition to the SH2 domain, the Pro-rich amino-terminal region of Grb10 was implicated in the regulation of PI 3-kinase catalytic activity. These regulatory roles of Grb10 were extended to specific insulin mediators downstream of PI 3-kinase including PKB/Akt, glycogen synthase kinase, and glycogen synthase. In contrast, a regulatory role of Grb10 in parallel insulin response pathways including p70 S6 kinase, ubiquitin ligase Cbl, or mitogen-activated protein kinase p38 was not observed. The dissection of the interaction of mouse Grb10 with p85 and the resulting regulation of PI 3-kinase activity should help elucidate the complexity of the IR signaling

Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target.

PubMed

Watson, Gabrielle M; Lucas, William A H; Gunzburg, Menachem J; Wilce, Jacqueline A

2017-01-01

Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors.

Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target

PubMed Central

Watson, Gabrielle M.; Lucas, William A. H.; Gunzburg, Menachem J.; Wilce, Jacqueline A.

2017-01-01

Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors. PMID:29018805

Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.

PubMed

Schlaepfer, D D; Hanks, S K; Hunter, T; van der Geer, P

The cytoplasmic focal adhesion protein-tyrosine kinase (FAK) localizes with surface integrin receptors at sites where cells attach to the extracellular matrix. Increased FAK tyrosine phosphorylation occurs upon integrin engagement with fibronectin. Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein kinase (MAPK). In v-Src-transformed NIH3T3, the association of v-Src, GRB2 and Sos with FAK is independent of cell adhesion to fibronectin. The GRB2 SH2 domain binds directly to tyrosine-phosphorylated FAK. Mutation of tyrosine residue 925 of FAK (YENV motif) to phenylalanine blocks GRB2 SH2-domain binding to FAK in vitro. Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK association and formation of an integrin-activated signalling complex. Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2-binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduction pathway.

GRB 090423 IN the Fireshell Scenario: a Canonical GRB at Redshift 8.2

NASA Astrophysics Data System (ADS)

Izzo, Luca; Bernardini, Maria Grazia; Bianco, Carlo Luciano; Caito, Letizia; Patricelli, Barbara; Ruffini, Remo

GRB 090423 is the farthest GRB up to date, with a redshift of about 8.1. We present within the Fireshell scenario a complete analysis of this GRB in the γ-ray band and a detailed analysis also in the X-rays, where we note the existence of a second component. We obtain that the FireShell model gives a good indication for the energetic emitted in the burst, Etot = 1:2x1053 ergs. Moreover we note that GRB 090423 is a long GRB with a relatively high bulk Lorentz Gamma factor at the transparency of the Fireshell. Finally we present a study of this extra component in the context of the synchrotron emission scenario, delineated in.8

The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.

PubMed

Rozakis-Adcock, M; Fernley, R; Wade, J; Pawson, T; Bowtell, D

1993-05-06

Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells.

Growth Factor Receptor–Bound Protein 2 Contributes to (Hem)Immunoreceptor Tyrosine-Based Activation Motif–Mediated Signaling in Platelets

PubMed Central

Morowski, Martina; Schiessl, Sarah; Schäfer, Carmen M.; Watson, Stephanie K.; Hughes, Craig E.; Ackermann, Jochen A.; Radtke, Daniel; Hermanns, Heike M.; Watson, Steve P.; Nitschke, Lars; Nieswandt, Bernhard

2015-01-01

Rationale Platelets are anuclear cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity but may also cause pathological vessel occlusion. One major pathway of platelet activation is triggered by 2 receptors that signal through an (hem)immunoreceptor tyrosine-based activation motif (ITAM), the activating collagen receptor glycoprotein (GP) VI and the C-type lectin-like receptor 2 (CLEC-2). Growth factor receptor–bound protein 2 (Grb2) is a ubiquitously expressed adapter molecule involved in signaling processes of numerous receptors in different cell types, but its function in platelets and MKs is unknown. Objective We tested the hypothesis that Grb2 is a crucial adapter protein in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets. Methods and Results Here, we show that genetic ablation of Grb2 in MKs and platelets did not interfere with MK differentiation or platelet production. However, Grb2-deficiency severely impaired glycoprotein VI–mediated platelet activation because of defective stabilization of the linker of activated T-cell (LAT) signalosome and activation of downstream signaling proteins that resulted in reduced adhesion, aggregation, and coagulant activity on collagen in vitro. Similarly, CLEC-2–mediated signaling was impaired in Grb2-deficient platelets, whereas the cells responded normally to stimulation of G protein–coupled receptors. In vivo, this selective (hem) immunoreceptor tyrosine-based activation motif signaling defect resulted in prolonged bleeding times but affected arterial thrombus formation only after concomitant treatment with acetylsalicylic acid, indicating that defective glycoprotein VI signaling in the absence of Grb2 can be compensated through thromboxane A2–induced G protein–coupled receptor signaling pathways. Conclusions These results reveal an important contribution of Grb2 in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets in

p56Lck and p59Fyn Regulate CD28 Binding to Phosphatidylinositol 3-Kinase, Growth Factor Receptor-Bound Protein GRB-2, and T Cell-Specific Protein-Tyrosine Kinase ITK: Implications for T-Cell Costimulation

NASA Astrophysics Data System (ADS)

Raab, Monika; Cai, Yun-Cai; Bunnell, Stephen C.; Heyeck, Stephanie D.; Berg, Leslie J.; Rudd, Christopher E.

1995-09-01

T-cell activation requires cooperative signals generated by the T-cell antigen receptor ξ-chain complex (TCRξ-CD3) and the costimulatory antigen CD28. CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS). PI 3-kinase and GRB-2 bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of intrinsic Src-homology 2 (SH2) domains. The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Candidate kinases include p56Lck, p59Fyn, ξ-chain-associated 70-kDa protein (ZAP-70), and ITK. In this study, we demonstrate in coexpression studies that p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28. Phosphatase digestion of CD28 eliminated binding. In contrast to Src kinases, ZAP-70 and ITK failed to induce these events. Further, ITK binding to CD28 was dependent on the presence of p56Lck and is thus likely to act downstream of p56Lck/p59Fyn in a signaling cascade. p56Lck is therefore likely to be a central switch in T-cell activation, with the dual function of regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling.

GRB2 Interaction with the Ecotropic Murine Leukemia Virus Receptor, mCAT-1, Controls Virus Entry and Is Stimulated by Virus Binding

PubMed Central

Chen, Zeming; Kolokoltsov, Andrey A.; Wang, Jia; Adhikary, Shramika; Lorinczi, Marta; Elferink, Lisa A.

2012-01-01

For retroviruses such as HIV-1 and murine leukemia virus (MLV), active receptor recruitment and trafficking occur during viral entry. However, the underlying mechanisms and cellular factors involved in the process are largely uncharacterized. The viral receptor for ecotropic MLV (eMLV), a classical model for retrovirus infection mechanisms and pathogenesis, is mouse cationic amino acid transporter 1 (mCAT-1). Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein that has been shown to couple cell surface receptors, such as epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor, to intracellular signaling events. Here we examined if GRB2 could also play a role in controlling infection by retroviruses by affecting receptor function. The GRB2 RNA interference (RNAi)-mediated suppression of endogenous GRB2 resulted in a consistent and significant reduction of virus binding and membrane fusion. The binding between eMLV and cells promoted increased GRB2–mCAT-1 interactions, as detected by immunoprecipitation. Consistently, the increased colocalization of GRB2 and mCAT-1 signals was detected by confocal microscopy. This association was time dependent and paralleled the kinetics of cell-virus membrane fusion. Interestingly, unlike the canonical binding pattern seen for GRB2 and growth factor receptors, GRB2–mCAT-1 binding does not depend on the GRB2-SH2 domain-mediated recognition of tyrosine phosphorylation on the receptor. The inhibition of endogenous GRB2 led to a reduction in surface levels of mCAT-1, which was detected by immunoprecipitation and by a direct binding assay using a recombinant MLV envelope protein receptor binding domain (RBD). Consistent with this observation, the expression of a dominant negative GRB2 mutant (R86K) resulted in the sequestration of mCAT-1 from the cell surface into intracellular vesicles. Taken together, these findings suggest a novel role for GRB2 in ecotropic MLV entry and infection by

GRB2 interaction with the ecotropic murine leukemia virus receptor, mCAT-1, controls virus entry and is stimulated by virus binding.

PubMed

Chen, Zeming; Kolokoltsov, Andrey A; Wang, Jia; Adhikary, Shramika; Lorinczi, Marta; Elferink, Lisa A; Davey, Robert A

2012-02-01

For retroviruses such as HIV-1 and murine leukemia virus (MLV), active receptor recruitment and trafficking occur during viral entry. However, the underlying mechanisms and cellular factors involved in the process are largely uncharacterized. The viral receptor for ecotropic MLV (eMLV), a classical model for retrovirus infection mechanisms and pathogenesis, is mouse cationic amino acid transporter 1 (mCAT-1). Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein that has been shown to couple cell surface receptors, such as epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor, to intracellular signaling events. Here we examined if GRB2 could also play a role in controlling infection by retroviruses by affecting receptor function. The GRB2 RNA interference (RNAi)-mediated suppression of endogenous GRB2 resulted in a consistent and significant reduction of virus binding and membrane fusion. The binding between eMLV and cells promoted increased GRB2-mCAT-1 interactions, as detected by immunoprecipitation. Consistently, the increased colocalization of GRB2 and mCAT-1 signals was detected by confocal microscopy. This association was time dependent and paralleled the kinetics of cell-virus membrane fusion. Interestingly, unlike the canonical binding pattern seen for GRB2 and growth factor receptors, GRB2-mCAT-1 binding does not depend on the GRB2-SH2 domain-mediated recognition of tyrosine phosphorylation on the receptor. The inhibition of endogenous GRB2 led to a reduction in surface levels of mCAT-1, which was detected by immunoprecipitation and by a direct binding assay using a recombinant MLV envelope protein receptor binding domain (RBD). Consistent with this observation, the expression of a dominant negative GRB2 mutant (R86K) resulted in the sequestration of mCAT-1 from the cell surface into intracellular vesicles. Taken together, these findings suggest a novel role for GRB2 in ecotropic MLV entry and infection by facilitating

Structural and biophysical investigation of the interaction of a mutant Grb2 SH2 domain (W121G) with its cognate phosphopeptide.

PubMed

Papaioannou, Danai; Geibel, Sebastian; Kunze, Micha B A; Kay, Christopher W M; Waksman, Gabriel

2016-03-01

The adaptor protein Grb2 is a key element of mitogenetically important signaling pathways. With its SH2 domain it binds to upstream targets while its SH3 domains bind to downstream proteins thereby relaying signals from the cell membranes to the nucleus. The Grb2 SH2 domain binds to its targets by recognizing a phosphotyrosine (pY) in a pYxNx peptide motif, requiring an Asn at the +2 position C-terminal to the pY with the residue either side of this Asn being hydrophobic. Structural analysis of the Grb2 SH2 domain in complex with its cognate peptide has shown that the peptide adopts a unique β-turn conformation, unlike the extended conformation that phosphopeptides adopt when bound to other SH2 domains. TrpEF1 (W121) is believed to force the peptide into this unusual conformation conferring this unique specificity to the Grb2 SH2 domain. Using X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and isothermal titration calorimetry (ITC), we describe here a series of experiments that explore the role of TrpEF1 in determining the specificity of the Grb2 SH2 domain. Our results demonstrate that the ligand does not adopt a pre-organized structure before binding to the SH2 domain, rather it is the interaction between the two that imposes the hairpin loop to the peptide. Furthermore, we find that the peptide adopts a similar structure when bound to both the wild-type Grb2 SH2 domain and a TrpEF1Gly mutant. This suggests that TrpEF1 is not the determining factor for the conformation of the phosphopeptide. © 2015 The Protein Society.

Grb2 mediates semaphorin-4D-dependent RhoA inactivation.

PubMed

Sun, Tianliang; Krishnan, Rameshkumar; Swiercz, Jakub M

2012-08-01

Signaling through the semaphorin 4D (Sema4D) receptor plexin-B1 is modulated by its interaction with tyrosine kinases ErbB-2 and Met. In cells expressing the plexin-B1-ErbB-2 receptor complex, ligand stimulation results in the activation of small GTPase RhoA and stimulation of cellular migration. By contrast, in cells expressing plexin-B1 and Met, ligand stimulation results in an association with the RhoGTPase-activating protein p190 RhoGAP and subsequent RhoA inactivation--a process that involves the tyrosine phosphorylation of plexin-B1 by Met. Inactivation of RhoA is necessary for Sema4D-mediated inhibition of cellular migration. It is, however, unknown how plexin-B1 phosphorylation regulates RhoGAP interaction and activity. Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Grb2 is thereby recruited into the plexin-B1 receptor complex and, through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation. Phosphorylation of plexin-B1 by Met and the recruitment of Grb2 have no effect on the R-RasGAP activity of plexin-B1, but are required for Sema4D-induced, RhoA-dependent antimigratory effects of Sema4D on breast cancer cells. These data show Grb2 as a direct link between plexin and p190-RhoGAP-mediated downstream signaling.

Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

PubMed

Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

2013-01-01

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation.

PubMed

Yang, Lan; Wen, Ya; Lv, Guoqing; Lin, Yuntao; Tang, Junlong; Lu, Jingxiao; Zhang, Manqiao; Liu, Wen; Sun, Xiaojuan

2017-12-09

Alpha lipoic acid (α -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, α -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of α -LA on non-small cell lung cancer (NSCLC) development remain unclear. The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after α -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting. Grb2 levels were restored in α-LA-treated cells by transfection of a plasmid carrying Grb2 and were reduced in NSCLC cells via specific siRNA-mediated knockdown. α -LA dramatically decreased NSCLC cell proliferation by downregulating Grb2; in contrast, Grb2 overexpression significantly prevented α-LA-induced decrease in cell growth in vitro. Western blot analysis indicated that α-LA decreased the levels of phospho-EGFR, CDK2/4/6, Cyclins D3 and E1, which are associated with the inhibition of G1/S-phase transition. Additional experiments indicated that Grb2 inhibition partially abolished EGF-induced phospho-EGFR and phospho-ERK1/2 activity. In addition, α-LA exerted greater inhibitory effects than gefitinib on NSCLC cells by preventing EGF-induced EGFR activation. For the first time, these findings provide the first evidence that α-LA inhibits cell proliferation through Grb2 by suppressing EGFR phosphorylation and that MAPK/ERK is involved in this pathway. Copyright © 2017. Published by Elsevier Inc.

Identification of GRB2 and GAB1 Coexpression as an Unfavorable Prognostic Factor for Hepatocellular Carcinoma by a Combination of Expression Profile and Network Analysis

PubMed Central

Yang, Mei; Wang, Danhua; Yu, Lingxiang; Guo, Chaonan; Guo, Xiaodong; Lin, Na

2013-01-01

Aim To screen novel markers for hepatocellular carcinoma (HCC) by a combination of expression profile, interaction network analysis and clinical validation. Methods HCC significant molecules which are differentially expressed or had genetic variations in HCC tissues were obtained from five existing HCC related databases (OncoDB.HCC, HCC.net, dbHCCvar, EHCO and Liverome). Then, the protein-protein interaction (PPI) network of these molecules was constructed. Three topological features of the network ('Degree', 'Betweenness', and 'Closeness') and the k-core algorithm were used to screen candidate HCC markers which play crucial roles in tumorigenesis of HCC. Furthermore, the clinical significance of two candidate HCC markers growth factor receptor-bound 2 (GRB2) and GRB2-associated-binding protein 1 (GAB1) was validated. Results In total, 6179 HCC significant genes and 977 HCC significant proteins were collected from existing HCC related databases. After network analysis, 331 candidate HCC markers were identified. Especially, GAB1 has the highest k-coreness suggesting its central localization in HCC related network, and the interaction between GRB2 and GAB1 has the largest edge-betweenness implying it may be biologically important to the function of HCC related network. As the results of clinical validation, the expression levels of both GRB2 and GAB1 proteins were significantly higher in HCC tissues than those in their adjacent nonneoplastic tissues. More importantly, the combined GRB2 and GAB1 protein expression was significantly associated with aggressive tumor progression and poor prognosis in patients with HCC. Conclusion This study provided an integrative analysis by combining expression profile and interaction network analysis to identify a list of biologically significant HCC related markers and pathways. Further experimental validation indicated that the aberrant expression of GRB2 and GAB1 proteins may be strongly related to tumor progression and prognosis

High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

PubMed

Higo, Kunitake; Ikura, Teikichi; Oda, Masayuki; Morii, Hisayuki; Takahashi, Jun; Abe, Ryo; Ito, Nobutoshi

2013-01-01

Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

Grb7 is over-expressed in cervical cancer and facilitate invasion and inhibit apoptosis in cervical cancer cells.

PubMed

Zhao, Hong-Bing; Zhang, Xi-Feng; Jia, Xue-Lin; Wang, Hao-Bin

2017-09-01

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34.2%, which was significantly higher than that in adjacent non-cancerous cervical tissue (0%, p<0.05). The expression of Grb7 was found to be correlated with age, tumor size, serosal invasion, differentiated degree, tumor stage, early or advanced stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with positive Grb7 protein expression had a lower overall survival rate than patients without Grb7 expression. In addition, Grb7 plays an important role in promoting tumor progression, including invasion and anti-apoptosis, in cervical cancer cell line. Down-regulation of Grb7 repressed the expression of MMP-9 and Bcl-2, and increased the expression of Bax in Grb7 knockdown Hela cells. Cell invasion assay showed decreased number of Grb7 knockdown Hela cells (18.7±2.1) compared to Hela cells (65.3±2.5, P<0.05). Our results indicated that Grb7 over-expression may facilitate invasion and inhibit apoptosis in cervical cancer and Grb7 is a potentially molecular target of cervical cancer chemotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion and branching morphogenesis by antagonists of Grb2 Src homology 2 domain interactions.

PubMed

Atabey, N; Gao, Y; Yao, Z J; Breckenridge, D; Soon, L; Soriano, J V; Burke, T R; Bottaro, D P

2001-04-27

Hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets during development, homeostasis and tissue regeneration. Inappropriate HGF signaling occurs in several human cancers, and the ability of HGF to initiate a program of protease production, cell dissociation, and motility has been shown to promote cellular invasion and is strongly linked to tumor metastasis. Upon HGF binding, several tyrosines within the intracellular domain of its receptor, c-Met, become phosphorylated and mediate the binding of effector proteins, such as Grb2. Grb2 binding through its SH2 domain is thought to link c-Met with downstream mediators of cell proliferation, shape change, and motility. We analyzed the effects of Grb2 SH2 domain antagonists on HGF signaling and observed potent blockade of cell motility, matrix invasion, and branching morphogenesis, with ED(50) values of 30 nm or less, but only modest inhibition of mitogenesis. These compounds are 1000-10,000-fold more potent anti-motility agents than any previously characterized Grb2 SH2 domain antagonists. Our results suggest that SH2 domain-mediated c-Met-Grb2 interaction contributes primarily to the motogenic and morphogenic responses to HGF, and that these compounds may have therapeutic application as anti-metastatic agents for tumors where the HGF signaling pathway is active.

Application of Ring-Closing Metathesis to Grb2 SH3 Domain-Binding Peptides | Center for Cancer Research

Cancer.gov

In silico-generated hypothetical interactions of a ring-closing metathesis-macrocylized peptide bound to the amino terminal SH3 domain of the growth factor receptor bound protein 2 (Grb2). The complex was derived from the NMR solution structure of the bound parent peptide, Ac-V-P-P-P-V-P-P-R-R-R-amide (Protein Data Bank: 3GBQ). The protein surface is shown as electrostatic

SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

PubMed

Anafi, M; Kiefer, F; Gish, G D; Mbamalu, G; Iscove, N N; Pawson, T

1997-10-31

Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.

Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation.

PubMed Central

Bazenet, C E; Gelderloos, J A; Kazlauskas, A

1996-01-01

Following binding of platelet-derived growth factor (PDGF), the PDGF alpha receptor (alphaPDGFR) becomes tyrosine phosphorylated and associates with a number of signal transduction molecules, including phospholipase Cgamma-1 (PLCgamma-1), phosphatidylinositol 3-kinase (PI3K), the phosphotyrosine phosphatase SHP-2, Grb2, and Src. Here, we present data identifying a novel phosphorylation site in the kinase insert domain of the alphaPDGFR at tyrosine (Y) 720. We replaced this residue with phenylalanine and expressed the mutated receptor (F720) in Patch fibroblasts that do not express the alphaPDGFR. Characterization of the F720 mutant indicated that binding of two proteins, SHP-2 and Grb2, was severely impaired, whereas PLCgamma-1 and PI3K associated to wild-type levels. In addition, mutating Y720 to phenylalanine dramatically reduced PDGF-dependent tyrosine phosphorylation of SHP-2. Since Y720 was required for recruitment of two proteins, we investigated the mechanism by which these two proteins associated with the alphaPDGFR. SHP-2 bound the alphaPDGFR directly, whereas Grb2 associated indirectly, most probably via SHP-2, as Grb2 and SHP-2 coimmunoprecipitated when SHP-2 was tyrosine phosphorylated. We also compared the ability of the wild-type and F720 alphaPDGFRs to mediate a number of downstream events. Preventing the alphaPDGFR from recruiting SHP-2 and Grb2 did not compromise PDGF-AA-induced activation of Ras, initiation of DNA synthesis, or growth of cells in soft agar. We conclude that phosphorylation of the alphaPDGFR at Y720 is required for association of SHP-2 and Grb2 and tyrosine phosphorylation of SHP-2; however, these events are not required for the alphaPDGFR to activate Ras or initiate a proliferative response. In addition, these findings reveal that while SHP-2 binds to both of the receptors, it binds in different locations: to the carboxy terminus of the betaPDGFR but to the kinase insert of the alphaPDGFR. PMID:8943348

Expression, refolding and crystallizations of the Grb2-like (GADS) C-terminal SH3 domain complexed with a SLP-76 motif peptide

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

Faravelli, Alessandro; Dimasi, Nazzareno, E-mail: ndimasi@gmail.com

Several crystals of the Grb2-like C-terminal SH3 domain in complex with a motif peptide from the SLP-76 protein were obtained and characterized. The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain. GADS interacts through its C-terminal SH3 domain with the adaptor protein SLP-76, thus recruiting this protein and other associated molecules to the linker for activation of T-cell (LAT) protein. The DNA encoding the C-terminal SH3 domain of GADS (GADS-cSH3) was assembled synthetically using a recursive PCR technique and the protein was overexpressed in Escherichia coli,more » refolded and purified. Several crystals of this domain in complex with the SLP-76 peptide were obtained and characterized.« less

In brain, Axl recruits Grb2 and the p85 regulatory subunit of Pl3 kinase; in vitro mutagenesis defines th requisite binding sites for downstream Akt activation

PubMed Central

Weinger, Jason G.; Gohari, Pouyan; Yan, Ying; Backer, Jonathan M.; Varnum, Brian; Shafit-Zagardo, Bridget

2010-01-01

Axl is a receptor tyrosine kinase implicated in cell survival following growth factor withdrawal and other stressors. The binding of Axl's ligand, growth arrest-specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of signaling molecules, and activation of downstream survival pathways. Pull-down assays and immunoprecipitations using wildtype and mutant Axl transfected cells determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an interaction between p85's second proline-rich region and the N-terminal SH3 domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM site. Gas6-stimulation of Axl-transfected COS7 cells recruited activated PI3 kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and O4– flow-through prepared from day 10 mouse brain, indicating that cells with active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways. PMID:18346204

GRB 170817A: a short GRB seen off-axis

NASA Astrophysics Data System (ADS)

He, Xin-Bo; Tam, Pak-Hin Thomas; Shen, Rong-Feng

2018-04-01

The angular distribution of gamma-ray burst (GRB) jets is not yet clear. The observed luminosity of GRB 170817A is the lowest among all known short GRBs, which is best explained by the fact that our line of sight is outside of the jet opening angle, θ obs > θ j , where θ obs is the angle between our line of sight and the jet axis. As inferred by gravitational wave observations, as well as radio and X-ray afterglow modeling of GRB 170817A, it is likely that θ obs ∼ 20° – 28°. In this work, we quantitatively consider two scenarios of angular energy distribution of GRB ejecta: a top-hat jet and a structured jet with a power law index s. For the top-hat jet model, we get a large θ j (e.g., θ j > 10°), a rather high local (i.e., z < 0.01) short GRB rate ∼8–15×103, Gpc‑3, yr‑1 (estimated to be 90∼1850 Gpc‑3, yr‑1 in Fong et al.) and an extremely high E peak,0 (on-axis, rest-frame) > 7.5 × 104, keV (∼500, keV for a typical short GRB). For the structured jet model, we use θ obs to give limits on s and θj for typical on-axis luminosity of a short GRB (e.g., 1049 erg s‑1 ∼ 1051 erg s‑1), and a low on-axis luminosity case (e.g., 1049 erg s‑1) gives more reasonable values of s. The structured jet model is more feasible for GRB 170817A than the top-hat jet model due to the rather high local short GRB rate, and the extremely high on-axis E peak,0 almost rules out the top-hat jet model. GRB 170817A is likely a low on-axis luminosity GRB (1049 erg s‑1) with a structured jet.

GRB 070610: A Curious Galactic Transient

NASA Astrophysics Data System (ADS)

Kasliwal, M. M.; Cenko, S. B.; Kulkarni, S. R.; Cameron, P. B.; Nakar, E.; Ofek, E. O.; Rau, A.; Soderberg, A. M.; Campana, S.; Bloom, J. S.; Perley, D. A.; Pollack, L. K.; Barthelmy, S.; Cummings, J.; Gehrels, N.; Krimm, H. A.; Markwardt, C. B.; Sato, G.; Chandra, P.; Frail, D.; Fox, D. B.; Price, P. A.; Berger, E.; Grebenev, S. A.; Krivonos, R. A.; Sunyaev, R. A.

2008-05-01

GRB 070610 is a typical high-energy event with a duration of 5 s. Yet within the burst localization we detect a highly unusual X-ray and optical transient, Swift J195509.6+261406. We see high-amplitude X-ray and optical variability on very short timescales even at late times. Using near-infrared imaging assisted by a laser guide star and adaptive optics, we identified the counterpart of Swift J195509.6+261406. Late-time optical and near-infrared imaging constrain the spectral type of the counterpart to be fainter than a K-dwarf, assuming it is of Galactic origin. It is possible that GRB 070610 and Swift J195509.6+261406 are unrelated sources. However, the absence of a typical X-ray afterglow from GRB 070610 in conjunction with the spatial and temporal coincidence of the two motivate us to suggest that the sources are related. The closest (imperfect) analog to Swift J195509.6+261406 is V4641 Sgr, an unusual black hole binary. We suggest that Swift J195509.6+261406 along with V4641 Sgr define a subclass of stellar black hole binaries—the fast X-ray novae. We further suggest that fast X-ray novae are associated with bursts of gamma rays. If so, GRB 070610 defines a new class of celestial gamma-ray bursts and these bursts dominate the long-duration GRB demographics.

GRB 060614 in the canonical fireshell model

NASA Astrophysics Data System (ADS)

Caito, L.; Bernardini, M. G.; Bianco, C. L.; Dainotti, M. G.; Guida, R.; Ruffini, R.

2008-10-01

Gamma-Ray Burst (GRB) 060614 is the first nearby long duration GRB clearly not associated to any bright Ib/c Supernova. The explosion of this burst undermines one of the fundamental assumptions of the standard scenario and opens new horizons and hints of investigation. GRB 060614, hardly classifiable as a short GRB, is not either a ``typical'' long GRB since it occurs in a low star forming region. Moreover, it presents deep similarities with GRB 970228, which is the prototype of the ``fake'' short bursts, or better canonical GRBs disguised as short ones. Within the ``fireshell'' model ([1]), we test if this ``anomalous'' source can be a disguised short GRB([2]).

Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7

NASA Astrophysics Data System (ADS)

Gunzburg, Menachem J.; Kulkarni, Ketav; Watson, Gabrielle M.; Ambaye, Nigus D.; Del Borgo, Mark P.; Brandt, Rebecca; Pero, Stephanie C.; Perlmutter, Patrick; Wilce, Matthew C. J.; Wilce, Jacqueline A.

2016-06-01

The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7-SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms an alternative contact with the surface of the target protein. Based on this structural information, we designed a new series of bicyclic G7 peptides that progressively constrain the starting peptide, to arrive at the G7-B4 peptide that binds with an approximately 2-fold enhanced affinity to the Grb7-SH2 domain (KD = 0.83 μM) compared to G7-B1 and shows low affinity binding to Grb2-, Grb10- and Grb14-SH2 domains (KD > 100 μM). Furthermore, we determined the structure of the G7-B4 bicyclic peptide in complex with the Grb7-SH2 domain, both before and after ring closing metathesis to show that the closed staple is essential to the target interaction. The G7-B4 peptide represents an advance in the development of Grb7 inhibitors and is a classical example of structure aided inhibitor development.

Long High Redshift GRB and Xrt/swift Lightcurves

NASA Astrophysics Data System (ADS)

Arkhangelskaja, Irene

At February of 2010 the volume of Swift GRB subset with known redshift consisted of more than 150 bursts. Long GRB redshift distribution analysis has shown that confidence level of single peak approximation of this distribution is only ˜60%. Moreover, more than 40% of GRB are in very heavy tails outside 3σ level for this fit. More detailed analysis of long GRB redshift distribution reveals that at 97% confidence level at least two subgroups could be separated with following parameters: = 0.9 ± 0.1 and 2> = 2.7 ± 0.2. It allows to make conclusion that Swift long GRB sources subset is not uniform. In the presented article attention is paid on the measure of discrepancy of long GRB with z>3 and subset of other long GRB with known redshifts. XRT/Swift lightcurves for these groups of GRB were considered and it have shown that at least 90% XRT/Swift lightcurves for GRB with z>3 are more complicated and have got a number of maxima.

Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization.

PubMed

Ramirez, Ursula D; Nikonova, Anna S; Liu, Hanqing; Pecherskaya, Anna; Lawrence, Sarah H; Serebriiskii, Ilya G; Zhou, Yan; Robinson, Matthew K; Einarson, Margret B; Golemis, Erica A; Jaffe, Eileen K

2015-05-28

Overexpression or mutation of the epidermal growth factor receptor (EGFR) potently enhances the growth of many solid tumors. Tumor cells frequently display resistance to mechanistically-distinct EGFR-directed therapeutic agents, making it valuable to develop therapeutics that work by additional mechanisms. Current EGFR-targeting therapeutics include antibodies targeting the extracellular domains, and small molecules inhibiting the intracellular kinase domain. Recent studies have identified a novel prone extracellular tetrameric EGFR configuration, which we identify as a potential target for drug discovery. Our focus is on the prone EGFR tetramer, which contains a novel protein-protein interface involving extracellular domain III. This EGFR tetramer is computationally targeted for stabilization by small molecule ligand binding. This study performed virtual screening of a Life Chemicals, Inc. small molecule library of 345,232 drug-like compounds against a molecular dynamics simulation of protein-protein interfaces distinct to the novel tetramer. One hundred nine chemically diverse candidate molecules were selected and evaluated using a cell-based high-content imaging screen that directly assessed induced internalization of the EGFR effector protein Grb2. Positive hits were further evaluated for influence on phosphorylation of EGFR and its effector ERK1/2. Fourteen hit compounds affected internalization of Grb2, an adaptor responsive to EGFR activation. Most hits had limited effect on cell viability, and minimally influenced EGFR and ERK1/2 phosphorylation. Docked hit compound poses generally include Arg270 or neighboring residues, which are also involved in binding the effective therapeutic cetuximab, guiding further chemical optimization. These data suggest that the EGFR tetrameric configuration offers a novel cancer drug target.

GRB070610: A Curious Galactic Transient

NASA Technical Reports Server (NTRS)

Kasliwal, M. M.; Kulkrarni. S. R.; Cameron, P. B.; Nakar, E.; Ofek, E. O.; Rau, A.; Soderberg, A. M.; Campana, S.; Bloom, J. S.; Perley, D. A.;

A Central Role for GRB10 in Regulation of Islet Function in Man

PubMed Central

Prasad B, Rashmi; Salehi, S. Albert; Almgren, Peter; Osmark, Peter; Bouatia-Naji, Nabila; Wierup, Nils; Fall, Tove; Stančáková, Alena; Barker, Adam; Lagou, Vasiliki; Osmond, Clive; Xie, Weijia; Lahti, Jari; Jackson, Anne U.; Cheng, Yu-Ching; Liu, Jie; O'Connell, Jeffrey R.; Blomstedt, Paul A.; Fadista, Joao; Alkayyali, Sami; Dayeh, Tasnim; Ahlqvist, Emma; Taneera, Jalal; Lecoeur, Cecile; Kumar, Ashish; Hansson, Ola; Hansson, Karin; Voight, Benjamin F.; Kang, Hyun Min; Levy-Marchal, Claire; Vatin, Vincent; Palotie, Aarno; Syvänen, Ann-Christine; Mari, Andrea; Weedon, Michael N.; Loos, Ruth J. F.; Ong, Ken K.; Nilsson, Peter; Isomaa, Bo; Tuomi, Tiinamaija; Wareham, Nicholas J.; Stumvoll, Michael; Widen, Elisabeth; Lakka, Timo A.; Langenberg, Claudia; Tönjes, Anke; Rauramaa, Rainer; Kuusisto, Johanna; Frayling, Timothy M.; Froguel, Philippe; Walker, Mark; Eriksson, Johan G.; Ling, Charlotte; Kovacs, Peter; Ingelsson, Erik; McCarthy, Mark I.; Shuldiner, Alan R.; Silver, Kristi D.; Laakso, Markku; Groop, Leif; Lyssenko, Valeriya

2014-01-01

Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father. PMID:24699409

Grb2-SH3 ligand inhibits the growth of HER2+ cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel.

PubMed

Gril, Brunilde; Vidal, Michel; Assayag, Franck; Poupon, Marie-France; Liu, Wang-Qing; Garbay, Christiane

2007-07-15

HER2 represents an important signaling pathway in breast and other cancers. Herceptin has demonstrated clinical activity, but resistance is common. Thus, new therapeutic approaches to the HER2 pathway are needed. Grb2 is an adaptor protein involved in Ras-dependent signaling induced by HER2 receptors. A specific Grb2-SH3 ligand, designed and synthesized in our laboratory, called peptidimer-c, inhibited colony formation in HER2 overexpressing SKBr3 cancer cells. Combined treatment of peptidimer-c with docetaxel further inhibited both colony formation and tumor cell survival compared to docetaxel treatment alone. Efficacy of this combined treatment was correlated with a reduction in the phosphorylation of MAPK and AKT. Finally, peptidimer-c reduced the growth of a HER2(+) human breast cancer (BK111) xenograft in nude mice and potentiated the antitumor effect of docetaxel in a HER2+ hormone-independent human prostate adenocarcinoma (PAC120 HID28) xenograft. These results validate Grb2 as a new target for the HER2 pathway. (c) 2007 Wiley-Liss, Inc.

Grb2-SH3 ligand inhibits the growth of HER2+ cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel

PubMed Central

Gril, Brunilde; Vidal, Michel; Assayag, Franck; Poupon, Marie-France; Liu, Wang-Qing; Garbay, Christiane

2007-01-01

HER2 represents an important signaling pathway in breast and other cancers. Herceptin has demonstrated clinical activity, but resistance is common. Thus, new therapeutic approaches to the HER2 pathway are needed. Grb2 is an adaptor protein involved in Ras-dependent signaling induced by HER2 receptors. A specific Grb2-SH3 ligand, designed and synthesized in our laboratory, called peptidimer-c, inhibited colony formation in HER2 over-expressing SKBr3 cancer cells. Combined treatment of peptidimer-c with docetaxel further inhibited both colony formation and tumor cell survival compared to docetaxel treatment alone. Efficacy of this combined treatment was correlated with a reduction in the phosphorylation of MAPK and AKT. Finally, peptidimer-c reduced the growth of a HER2+ human breast cancer (BK111) xenograft in nude mice and potentiated the anti-tumor effect of docetaxel in a HER2+ hormone-independent human prostate adenocarcinoma (PAC120 HID28) xenograft. These results validate Grb2 as a new target for the HER2 pathway. PMID:17372910

Epidermal growth factor-induced phosphatidylinositol 3-kinase activation and DNA synthesis. Identification of Grb2-associated binder 2 as the major mediator in rat hepatocytes.

PubMed

Kong, M; Mounier, C; Wu, J; Posner, B I

2000-11-17

In previous work we showed that the phosphatidylinositol 3-kinase (PI3-kinase), not the mitogen-activated protein kinase, pathway is necessary and sufficient to account for insulin- and epidermal growth factor (EGF)-induced DNA synthesis in rat hepatocytes. Here, using a dominant-negative p85, we confirmed the key role of EGF-induced PI3-kinase activation and sought to identify the mechanism by which this is effected. Our results show that EGF activates PI3-kinase with a time course similar to that of the association of p85 with three principal phosphotyrosine proteins (i. e. PY180, PY105, and PY52). We demonstrated that each formed a distinct p85-associated complex. PY180 and PY52 each constituted about 10% of EGF-activated PI3-kinase, whereas PY105 was responsible for 80%. PY105 associated with Grb2 and SHP-2, and although it behaved like Gab1, none of the latter was detected in rat liver. We therefore cloned a cDNA from rat liver, which was found to be 95% homologous to the mouse Grb2-associated binder 2 (Gab2) cDNA sequence. Using a specific Gab2 antibody, we demonstrated its expression in and association with p85, SHP-2, and Grb2 upon EGF treatment of rat hepatocytes. Gab2 accounted for most if not all of the PY105 species, since immunoprecipitation of Gab2 with specific antibodies demonstrated parallel immunodepletion of Gab2 and PY105 from the residual supernatants. We also found that the PI3-kinase activity associated with Gab2 was totally abolished by dominant negative p85. Thus, Gab2 appears to be the principal EGF-induced PY protein recruiting and activating PI3-kinase and mitogenesis.

GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2.

PubMed

Zhao, Chunmei; Ma, Hong; Bossy-Wetzel, Ella; Lipton, Stuart A; Zhang, Zhuohua; Feng, Gen-Sheng

2003-09-05

Gab1 and Gab2 are scaffolding proteins acting downstream of cell surface receptors and interact with a variety of cytoplasmic signaling proteins such as Grb2, Shp-2, phosphatidylinositol 3-kinase, Shc, and Crk. To identify new binding partners for GAB proteins and better understand their functions, we performed a yeast two-hybrid screening with hGab2-(120-587) as bait. This work led to identification of a novel GTPase-activating protein (GAP) for Rho family GTPases. The GAP domain shows high similarity to the recently cloned CdGAP and displays activity toward RhoA, Rac1, and Cdc42 in vitro. The protein was named GC-GAP for its ability to interact with GAB proteins and its activity toward Rac and Cdc42. GC-GAP is predominantly expressed in the brain with low levels detected in other tissues. Antibodies directed against GC-GAP recognized a protein of approximately 200 kDa. Expression of GC-GAP in 293T cells led to a reduction in active Rac1 and Cdc42 levels but not RhoA. Suppression of GC-GAP expression by siRNA inhibited proliferation of C6 astroglioma cells. In addition, GC-GAP contains several classic proline-rich motifs, and it interacts with the first SH3 domain of Crk and full-length Nck in vitro. We propose that Gab1 and Gab2 in cooperation with other adapter molecules might regulate the cellular localization of GC-GAP under specific stimuli, acting to regulate precisely Rac and Cdc42 activities. Given that GC-GAP is specifically expressed in the nervous system and that it is localized to the dendritic processes of cultured neurons, GC-GAP may play a role in dendritic morphogenesis and also possibly in neural/glial cell proliferation.

Protein tyrosine phosphatase-1B regulates the tyrosine phosphorylation of the adapter Grb2-associated binder 1 (Gab1) in the retina

PubMed Central

2013-01-01

Background Gab1 (Grb2-associated binder 1) is a key coordinator that belongs to the insulin receptor substrate-1 like family of adaptor molecules and is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules. Tyrosine phosphorylated Gab1 is able to recruit a number of signaling effectors including PI3K, SHP2 and PLC-γ. In this study, we characterized the localization and regulation of tyrosine phosphorylation of Gab1 in the retina. Results Our immuno localization studies suggest that Gab1 is expressed in rod photoreceptor inner segments. We found that hydrogen peroxide activates the tyrosine phosphorylation of Gab1 ex vivo and hydrogen peroxide has been shown to inhibit the protein tyrosine phosphatase PTP1B activity. We found a stable association between the D181A substrate trap mutant of PTP1B and Gab1. Our studies suggest that PTP1B interacts with Gab1 through Tyrosine 83 and this residue may be the major PTP1B target residue on Gab1. We also found that Gab1 undergoes a light-dependent tyrosine phosphorylation and PTP1B regulates the phosphorylation state of Gab1. Consistent with these observations, we found an enhanced Gab1 tyrosine phosphorylation in PTP1B deficient mice and also in retinas treated ex vivo with a PTP1B specific allosteric inhibitor. Conclusions Our laboratory has previously reported that retinas deficient of PTP1B are resistant to light damage compared to wild type mice. Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well. In summary, our data suggest that PTP1B regulates the phosphorylation state of retinal Gab1 in vivo. PMID:23521888

Amyloid precursor protein modulates ERK-1 and -2 signaling.

PubMed

Venezia, Valentina; Nizzari, Mario; Repetto, Emanuela; Violani, Elisabetta; Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Carlo, Pia; Schettini, Gennaro; Florio, Tullio; Russo, Claudio

2006-12-01

The amyloid precursor protein (APP) is a transmembrane protein with a short cytoplasmic tail whose physiological function is unclear, although it is well documented that the proteolytic processing of APP could influence the development of Alzheimer's disease (AD) through the formation of membrane-bound C-terminal fragments (CTFs) and of beta-amyloid peptides (Abeta). We have recently shown that tyrosine-phosphorylated APP and CTFs may interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent in AD subjects only. To study the interaction between APP or CTFs and ShcA/Grb2 and to investigate their molecular target we have used as experimental model two different cell lines: H4 human neuroglioma cells and APP/APLP null mouse embryonic fibroblast cells (MEFs). Here we show that in H4 cells APP interacts with Grb2; conversely in APP/APLP-null MEF cells this interaction is possible only after the reintroduction of human APP by transfection. We have also shown that in MEF cells the transfection of a plasmid encoding for human APP wild-type enhances the phosphorylation of ERK-1 and -2 as revealed by Western blotting and immunofluorescence experiments. Finally, also in H4 cells the overexpression of APP upregulates the levels of phospho-ERK-1 and -2. In summary our data suggest that APP may influence phospho-ERK-1 and -2 signaling through its binding with Grb2 and ShcA adaptors. The meaning of this event is not clear, but APP interaction with these adaptors could be relevant to regulate mitogenic pathway.

The 'Supercritical Pile' GRB Model: Afterglows and GRB, XRR, XRF Unification

NASA Technical Reports Server (NTRS)

Kazanas, D.

2007-01-01

We present the general notions and observational consequences of the "Supercritical Pile" GRB model; the fundamental feature of this model is a detailed process for the conversion of the energy stored in relativistic protons in the GRB Relativistic Blast Waves (RBW) into relativistic electrons and then into radiation. The conversion is effected through the $p \\, \\gamma \\rightarrow p \\, e circumflex + e circumflex -$ reaction, whose kinematic threshold is imprinted on the GRB spectra to provide a peak of their emitted luminosity at energy \\Ep $\\sim 1$ MeV in the lab frame. We extend this model to include, in addition to the (quasi--)thermal relativistic post-shock protons an accelerated component of power law form. This component guarantees the production of $e circumflex +e circumflex- - $pairs even after the RBW has slowed down to the point that its (quasi-) thermal protons cannot fulfill the threshold of the above reaction. We suggest that this last condition marks the transition from the prompt to the afterglow GRB phase. We also discuss conditions under which this transition is accompanied by a significant drop in the flux and could thus account for several puzzling, recent observations. Finally, we indicate that the same mechanism applied to the late stages of the GRB evolution leads to a decrease in \\Ep $\\propto \\Gamma circumflex 2(t)\\propto t circumflex {-3/4}$, a feature amenable to future observational tests.

miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

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

Zhang, Yunda; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102; Xu, Guoxing

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasionmore » while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.« less

Very Large Telescope/Ultraviolet and Visual Echelle Spectrograph and FORS2 spectroscopy of the GRB 081008 afterglow

NASA Astrophysics Data System (ADS)

D'Elia, V.; Campana, S.; Covino, S.; D'Avanzo, P.; Piranomonte, S.; Tagliaferri, G.

2011-11-01

We aim at studying the gamma-ray burst (GRB), GRB 081008, environment by analysing the spectra of its optical afterglow. Ultraviolet and Visual Echelle Spectrograph/Very Large Telescope (UVES/VLT) high-resolution spectroscopy of GRB 081008 was secured ˜5 h after the Swift-BAT trigger. Our data set also comprises three VLT/FORS2 nearly simultaneous spectra of the same source. The availability of nearly simultaneous high- and low-resolution spectra for a GRB afterglow is an extremely rare event. The GRB-damped Lyman α system at z= 1.9683 shows that the interstellar medium (ISM) of the host galaxy is constituted by at least three components which contribute to the line profiles. Component I is the redmost one, and is 20 and 78 km s-1 redward components II and III, respectively. We detect several ground state and excited absorption features in components I and II. These features have been used to compute the distances between the GRB and the absorbers. Component I is found to be 52 ± 6 pc away from the GRB, while component II presents few excited transitions and its distance is 200+60- 80 pc. Component III only features a few, low-ionization and saturated lines suggesting that it is even farther from the GRB. Component I represents the closest absorber ever detected near a GRB. This (relatively) low distance can possibly be a consequence of a dense GRB environment, which prevents the GRB prompt/afterglow emission to strongly affect the ISM up to higher distances. The hydrogen column density associated with GRB 081008 is log NH/cm-2= 21.11 ± 0.10, and the metallicity of the host galaxy is in the range of [X/H] =-1.29 to -0.52. In particular, we found [Fe/H] =-1.19 ± 0.11 and [Zn/H] =-0.52 ± 0.11 with respect to solar values. This discrepancy can be explained by the presence of dust in the GRB ISM, given the opposite refractory properties of iron and zinc. By deriving the depletion pattern for GRB 081008, we find the optical extinction in the visual band to be AV�

Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1

PubMed Central

Deng, Haoyu; Fung, Gabriel; Shi, Junyan; Xu, Suowen; Wang, Chen; Yin, Meimei; Hou, Jun; Zhang, Jingchun; Jin, Zheng-Gen; Luo, Honglin

2015-01-01

Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2Apro, independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1–174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1–174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication.—Deng, H., Fung, G., Shi, J., Xu, S., Wang, C., Yin, M., Hou, J., Zhang, J., Jin, Z.-G., Luo, H. Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1. PMID:26183772

How Special Is GRB 170817A?

NASA Astrophysics Data System (ADS)

Yue, Chuan; Hu, Qian; Zhang, Fu-Wen; Liang, Yun-Feng; Jin, Zhi-Ping; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

2018-01-01

GRB 170817A is the first short gamma-ray burst (GRB) with direct detection of the gravitational-wave radiation and also the spectroscopically identified macronova emission (i.e., AT 2017gfo). The prompt emission of this burst, however, is underluminous in comparison with the other short GRBs with known redshift. In this work, we examine whether GRB 170817A is indeed unique. We first show that GRB 130603B/macronova may be the on-axis “analogs” of GRB 170817A/AT 2017gfo, and the extremely dim but long-lasting afterglow emission of GRB 170817A may suggest a low number density (∼ {10}-5 {{cm}}-3) of its circumburst medium and a structured outflow. We then discuss whether GRB 070923, GRB 080121, GRB 090417A, GRB 111005A, and GRB 170817A form a new group of very nearby underluminous GRBs originated from neutron star mergers. If the short events GRB 070923, GRB 080121, and GRB 090417A are indeed at a redshift of ∼ 0.076, 0.046, 0.088, respectively, their isotropic energies of the prompt emission are ∼ {10}47 erg and thus comparable to the other two events. The non-detection of optical counterparts of GRB 070923, GRB 080121, GRB 090417A, and GRB 111005A, however, strongly suggests that the macronovae from neutron star mergers are significantly diverse in luminosities or, alternatively, there is another origin channel (for instance, the white dwarf and black hole mergers). We finally suggest that GW170817/GRB 170817A are likely not alone and similar events will be detected by the upgraded/upcoming gravitational-wave detectors and the electromagnetic monitors.

The Macronova in GRB 050709 and the GRB-macronova connection

PubMed Central

Jin, Zhi-Ping; Hotokezaka, Kenta; Li, Xiang; Tanaka, Masaomi; D'Avanzo, Paolo; Fan, Yi-Zhong; Covino, Stefano; Wei, Da-Ming; Piran, Tsvi

2016-01-01

GRB 050709 was the first short Gamma-ray Burst (sGRB) with an identified optical counterpart. Here we report a reanalysis of the publicly available data of this event and the discovery of a Li-Paczynski macronova/kilonova that dominates the optical/infrared signal at t>2.5 days. Such a signal would arise from 0.05 r-process material launched by a compact binary merger. The implied mass ejection supports the suggestion that compact binary mergers are significant and possibly main sites of heavy r-process nucleosynthesis. Furthermore, we have reanalysed all afterglow data from nearby short and hybrid GRBs (shGRBs). A statistical study of shGRB/macronova connection reveals that macronova may have taken place in all these GRBs, although the fraction as low as 0.18 cannot be ruled out. The identification of two of the three macronova candidates in the I-band implies a more promising detection prospect for ground-based surveys. PMID:27659791

GRB 140619B: a short GRB from a binary neutron star merger leading to black hole formation

NASA Astrophysics Data System (ADS)

Ruffini, R.; Muccino, M.; Kovacevic, M.; Oliveira, F. G.; Rueda, J. A.; Bianco, C. L.; Enderli, M.; Penacchioni, A. V.; Pisani, G. B.; Wang, Y.; Zaninoni, E.

2015-08-01

We show the existence of two families of short gamma-ray bursts (GRBs), both originating from the merger of binary neutron stars (NSs): family-1 with {E}{iso}\\lt {10}52 erg, leading to a massive NS as the merged core, and family-2 with {E}{iso}\\gt {10}52 erg, leading to a black hole (BH). Following the identification of the prototype GRB 090227B, we present the details of a new example of family-2 short burst: GRB 140619B. From the spectral analysis of the early ˜0.2 s, we infer an observed temperature {kT}=(324+/- 33) keV of the {{{e}}}+{{{e}}}--plasma at transparency (P-GRB), a theoretically derived redshift z=2.67+/- 0.37, a total burst energy {E}{{{e}}+{{{e}}}-}{tot}=(6.03+/- 0.79)× {10}52 erg, a rest-frame peak energy {E}p,i=4.7 MeV, and a baryon load B=(5.52+/- 0.73)× {10}-5. We also estimate the corresponding emission of gravitational waves. Two additional examples of family-2 short bursts are identified: GRB 081024B and GRB 090510, remarkable for its well determined cosmological distance. We show that marked differences exist in the nature of the afterglows of these two families of short bursts: family-2 bursts, leading to BH formation, consistently exhibit high energy emission following the proper-GRB emission; family-1 bursts, leading to the formation of a massive NS, should never exhibit high energy emission. We also show that both the families fulfill an {E}p,i-Eiso relation with slope γ =0.59+/- 0.07 and a normalization constant incompatible with the one for long GRBs. The observed rate of such family-2 events is {ρ }0=≤ft({2.1}-1.4+2.8\\right)× {10}-4 Gpc-3 yr-1.

Activated STAT5 proteins induce activation of the PI 3-kinase/Akt and Ras/MAPK pathways via the Gab2 scaffolding adapter.

PubMed

Nyga, Rémy; Pecquet, Christian; Harir, Noria; Gu, Haihua; Dhennin-Duthille, Isabelle; Régnier, Aline; Gouilleux-Gruart, Valérie; Lassoued, Kaïss; Gouilleux, Fabrice

2005-08-15

The active forms of STAT5A (signal transducer and activator of transcription 5A) and STAT5B are able to relieve the cytokine dependence of haematopoietic cells and to induce leukaemia in mice. We have demonstrated previously that activation of the PI3K (phosphoinositide 3-kinase) signalling cascade plays a major role in cell growth and survival induced by these proteins. Interaction between STAT5 and p85, the regulatory subunit of the PI3K, has been suggested to be required for this activation. We show in the present study that the scaffolding protein Gab2 [Grb2 (growth-factor-receptor-bound protein 2)-associated binder-2] is an essential component of this interaction. Gab2 is persistently tyrosine-phosphorylated in Ba/F3 cells expressing caSTAT5 (constitutively activated STAT5), independent of JAK2 (Janus kinase 2) activation where it interacts with STAT5, p85 and Grb2, but not with Shp2 [SH2 (Src homology 2)-domain-containing tyrosine phosphatase] proteins. Interaction of STAT5 with Gab2 was also observed in Ba/F3 cells stimulated with interleukin-3 or expressing the oncogenic fusion protein Tel-JAK2. The MAPKs (mitogen-activated protein kinases) ERK1 (extracellular-signal-regulated kinase 1) and ERK2 were constitutively activated in the caSTAT5-expressing cells and were found to be required for caSTAT5-induced cell proliferation. Overexpression of Gab2-3YF, a mutant of Gab2 incapable of binding PI3K, inhibited the proliferation and survival of caSTAT5-expressing cells as well as ERK1/2 and Akt/protein kinase B phosphorylation. Taken together, our results indicate that Gab2 is required for caSTAT5-induced cell proliferation by regulating both the PI3K/Akt and the Ras/MAPK pathways.

Activated STAT5 proteins induce activation of the PI 3-kinase/Akt and Ras/MAPK pathways via the Gab2 scaffolding adapter

PubMed Central

2005-01-01

The active forms of STAT5A (signal transducer and activator of transcription 5A) and STAT5B are able to relieve the cytokine dependence of haematopoietic cells and to induce leukaemia in mice. We have demonstrated previously that activation of the PI3K (phosphoinositide 3-kinase) signalling cascade plays a major role in cell growth and survival induced by these proteins. Interaction between STAT5 and p85, the regulatory subunit of the PI3K, has been suggested to be required for this activation. We show in the present study that the scaffolding protein Gab2 [Grb2 (growth-factor-receptor-bound protein 2)-associated binder-2] is an essential component of this interaction. Gab2 is persistently tyrosine-phosphorylated in Ba/F3 cells expressing caSTAT5 (constitutively activated STAT5), independent of JAK2 (Janus kinase 2) activation where it interacts with STAT5, p85 and Grb2, but not with Shp2 [SH2 (Src homology 2)-domain-containing tyrosine phosphatase] proteins. Interaction of STAT5 with Gab2 was also observed in Ba/F3 cells stimulated with interleukin-3 or expressing the oncogenic fusion protein Tel–JAK2. The MAPKs (mitogen-activated protein kinases) ERK1 (extracellular-signal-regulated kinase 1) and ERK2 were constitutively activated in the caSTAT5-expressing cells and were found to be required for caSTAT5-induced cell proliferation. Overexpression of Gab2-3YF, a mutant of Gab2 incapable of binding PI3K, inhibited the proliferation and survival of caSTAT5-expressing cells as well as ERK1/2 and Akt/protein kinase B phosphorylation. Taken together, our results indicate that Gab2 is required for caSTAT5-induced cell proliferation by regulating both the PI3K/Akt and the Ras/MAPK pathways. PMID:15833084

GRB 111005A at z = 0.0133 and the Prospect of Establishing Long-Short GRB/GW Association

NASA Astrophysics Data System (ADS)

Wang, Yuan-Zhu; Huang, Yong-Jia; Liang, Yun-Feng; Li, Xiang; Jin, Zhi-Ping; Zhang, Fu-Wen; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

2017-12-01

GRB 111005A, a long-duration gamma-ray burst (GRB) that occurred within a metal-rich environment that lacks massive stars with {M}{ZAMS}≥slant 15 {M}⊙ , is not coincident with supernova emission down to a stringent limit and thus should be classified as a “long-short” GRB (lsGRB; also known as an SN-less long GRB or hybrid GRB), like GRB 060505 and GRB 060614. In this work, we show that in the neutron star merger model the non-detection of the optical/infrared emission of GRB 111005A requires sub-relativistic neutron-rich ejecta with a mass of ≤slant 0.01 {M}⊙ , which is (significantly) less massive than that of GRB 130603B, GRB 060614, GRB 050709, and GRB 170817A. The lsGRBs are found to have a high rate density and the neutron star merger origin model can be unambiguously tested by the joint observations of the second-generation gravitational-wave (GW) detectors and the full-sky gamma-ray monitors such as Fermi-GBM and the proposed GECAM. If no lsGRB/GW association is observed in the 2020s, alternative scenarios have to be systematically investigated. With the detailed environmental information achievable for the nearby events, a novel kind of merger or explosion origin may be identified.

A Tale of Two Faint Bursts: GRB 050223 and GRB 050911

NASA Astrophysics Data System (ADS)

Page, K. L.; Barthelmy, S. D.; Beardmore, A. P.; Burrows, D. N.; Campana, S.; Chincharini, G.; Cummings, J. R.; Cusumano, G.; Gehrels, N.; Giommi, P.; Goad, M. R.; Godet, O.; Graham, J.; Kaneko, Y.; Kennea, J. A.; Mangano, V.; Markwardt, C. B.; O'Brien, P. T.; Osborne, J. P.; Reichart, D. E.; Rol, E.; Sakamoto, T.; Tagliaferri, G.; Tanvir, N. R.; Wells, A. A.; Zhang, B.

2006-05-01

GRBs 050223 and 050911 were discovered by the Swift Burst Alert Telescope (BAT) on 23rd February and 11th September 2005 respectively. The observation of GRB 050223 showed a faint, fading X-ray source, which was identified as the afterglow; GRB 050911, however, was not detected, making any X-ray afterglow extremely faint. The faintness of the afterglow of GRB 050223 could be explained by a large opening or viewing angle, or by the burst being at high redshift. The non-detection of GRB 050911 may indicate the burst occurred in a low-density environment, or, alternatively, was due to a compact object merger, in spite of the apparent long duration of the burst.

The GOES-R Rebroadcast (GRB) Data Stream Simulator

NASA Astrophysics Data System (ADS)

Dittberner, G. J.; Gibbons, K.; Czopkiewicz, E.; Miller, C.; Brown-Bergtold, B.; Haman, B.; Marley, S.

2013-12-01

GOES Rebroadcast (GRB) signals in the GOES-R era will replace the current legacy GOES Variable (GVAR) signal and will have substantially different characteristics, including a change in data rate from a single 2.1 Mbps stream to two digital streams of 15.5 Mbps each. Five GRB Simulators were developed as portable systems that output a high-fidelity stream of Consultative Committee for Space Data Systems (CCSDS) formatted GRB packet data equivalent to live GRB data. The data are used for on-site testing of user ingest and data handling systems known as field terminal sites. The GRB Simulator is a fully self-contained system which includes all software and hardware units needed for operation. The operator manages configurations to edit preferences, define individual test scenarios, and manage event logs and reports. Simulations are controlled by test scenarios, which are scripts that specify the test data and provide a series of actions for the GRB Simulator to perform when generating GRB output. Scenarios allow for the insertion of errors or modification of GRB packet headers for testing purposes. The GRB Simulator provides a built-in editor for managing scenarios. The GRB Simulator provides GRB data as either baseband (digital) or Intermediate Frequency (IF) output to the test system. GRB packet data are sent in the same two output streams used in the operational system: one for Left Hand Circular Polarization (LHCP) and one for Right Hand Circular Polarization (RHCP). Use of circular polarization in the operational system allows the transmitting antenna to multiplex the two digital streams into the same signal, thereby doubling the available bandwidth. The GRB Simulator is designed to be used at sites that receive the GRB downlink.

Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.

PubMed

Pruett, W; Yuan, Y; Rose, E; Batzer, A G; Harada, N; Skolnik, E Y

1995-03-01

Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context

Modeling the Multiband Afterglows of GRB 060614 and GRB 060908: Further Evidence for a Double Power-law Hard Electron Energy Spectrum

NASA Astrophysics Data System (ADS)

Zhang, Q.; Xiong, S. L.; Song, L. M.

2018-04-01

Electrons accelerated in relativistic collisionless shocks are usually assumed to follow a power-law energy distribution with an index of p. Observationally, although most gamma-ray bursts (GRBs) have afterglows that are consistent with p > 2, there are still a few GRBs suggestive of a hard (p < 2) electron energy spectrum. Our previous work showed that GRB 091127 gave strong evidence for a double power-law hard electron energy (DPLH) spectrum with 1 < p 1 < 2, p 2 > 2 and an “injection break” assumed as γ b ∝ γ q in the highly relativistic regime, where γ is the bulk Lorentz factor of the jet. In this paper, we show that GRB 060614 and GRB 060908 provide further evidence for such a DPLH spectrum. We interpret the multiband afterglow of GRB 060614 with the DPLH model in a homogeneous interstellar medium by taking into account a continuous energy injection process, while, for GRB 060908, a wind-like circumburst density profile is used. The two bursts, along with GRB 091127, suggest a similar behavior in the evolution of the injection break, with q ∼ 0.5. Whether this represents a universal law of the injection break remains uncertain and more afterglow observations such as these are needed to test this conjecture.

A New GRB follow-up Software at TUG

NASA Astrophysics Data System (ADS)

Dindar, M.; Parmaksizoglu, M.; Helhel, S.; Esenoglu, H.; Kirbiyik, H.

2016-12-01

A gamma-ray burst (GRB) optical photometric follow-up system at TUBITAK (Scientic and Technological Research Council of Turkey) National Observatory (TUG) has been planned. It uses the 0.6 m Telescope (T60) and can automatically respond to GRB Coordinates Network (GCN) alerts. The telescopes slew relatively fast, being able to point to a new target field within 30 s upon a request. Whenever available, the 1 m T100 and 2.5 m RTT150 telescopes will be used in the future. As an example in 2015, the GRB software system (will be server side) at T60-telescope responded to GRB alert and started the observation as early as 129 s after the GRB trigger autonomously.

Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.

PubMed

Yan, Xiao; Himburg, Heather A; Pohl, Katherine; Quarmyne, Mamle; Tran, Evelyn; Zhang, Yurun; Fang, Tiancheng; Kan, Jenny; Chao, Nelson J; Zhao, Liman; Doan, Phuong L; Chute, John P

2016-11-01

Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10 m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10 +/+ mice. After total body irradiation (TBI), Grb10 m/+ mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution, as compared to Grb10 +/+ mice. Grb10-deficient HSCs displayed increased proliferation after competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10-deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene Grb10 in regulating HSC self-renewal and regeneration and suggests that the inhibition of Grb10 can promote hematopoietic regeneration in vivo. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular Cloning and Characterization of Growth Factor Receptor Bound-Protein in Clonorchis sinensis

PubMed Central

Bai, Xuelian; Lee, Ji-Yun; Kim, Tae Im; Dai, Fuhong; Lee, Tae-Jin; Hong, Sung-Jong

2014-01-01

Background Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2) is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2) from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. Methodology/Principal Findings A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. Conclusion Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths. PMID:24454892

Maltose-Binding Protein Enhances Secretion of Recombinant Human Granzyme B Accompanied by In Vivo Processing of a Precursor MBP Fusion Protein

PubMed Central

Dälken, Benjamin; Jabulowsky, Robert A.; Oberoi, Pranav; Benhar, Itai; Wels, Winfried S.

2010-01-01

Background The apoptosis-inducing serine protease granzyme B (GrB) is an important factor contributing to lysis of target cells by cytotoxic lymphocytes. Expression of enzymatically active GrB in recombinant form is a prerequisite for functional analysis and application of GrB for therapeutic purposes. Methods and Findings We investigated the influence of bacterial maltose-binding protein (MBP) fused to GrB via a synthetic furin recognition motif on the expression of the MBP fusion protein also containing an N-terminal α-factor signal peptide in the yeast Pichia pastoris. MBP markedly enhanced the amount of GrB secreted into culture supernatant, which was not the case when GrB was fused to GST. MBP-GrB fusion protein was cleaved during secretion by an endogenous furin-like proteolytic activity in vivo, liberating enzymatically active GrB without the need of subsequent in vitro processing. Similar results were obtained upon expression of a recombinant fragment of the ErbB2/HER2 receptor protein or GST as MBP fusions. Conclusions Our results demonstrate that combination of MBP as a solubility enhancer with specific in vivo cleavage augments secretion of processed and functionally active proteins from yeast. This strategy may be generally applicable to improve folding and increase yields of recombinant proteins. PMID:21203542

Growth of chronic myeloid leukemia cells is inhibited by infection with Ad-SH2-HA adenovirus that disrupts Grb2-Bcr-Abl complexes.

PubMed

Peng, Zhi; Luo, Hong-Wei; Yuan, Ying; Shi, Jing; Huang, Shi-Feng; Li, Chun-Li; Cao, Wei-Xi; Huang, Zong-Gan; Feng, Wen-Li

2011-05-01

The persistence of Bcr-Abl-positive cells in patients on imatinib therapy indicates that inhibition of the Bcr-Abl kinase activity alone might not be sufficient to eradicate the leukemia cells. Many downstream effectors of Bcr-Abl have been described, including activation of both the Grb2-SoS-Ras-MAPK and Grb2-Gab2-PI3K-Akt pathways. The Bcr-Abl-Grb2 interaction, which is mediated by the direct interaction of the Grb2 SH2 domain with the phospho-Bcr-Abl Y177, is required for activation of these signaling pathways. Therefore, disrupting their interaction represents a potential therapeutic strategy for inhibiting the oncogenic downstream signals of Bcr-Abl. Adenovirus Ad-SH2-HA expressing the Grb2 SH2 domain was constructed and applied in this study. As expected, Ad-SH2-HA efficiently infected CML cells and functioned by binding to the phospho-Bcr-Abl Y177 site, competitively disrupting the Grb2 SH2-phospho-Bcr-Abl Y177 complex. They induced potent anti-proliferation and apoptosis-inducing effects in CML cell lines. Moreover, the Ras, MAPK and Akt activities were significantly reduced in the Ad-SH2-HA treated cells. These were not observed with the point-mutated control adenovirus Ad-Sm-HA with abolished phospho-Bcr-Abl Y177 binding sites. These data indicate that, in addition to the direct targeting of Bcr-Abl, selective inhibition of its downstream signaling pathways may be a therapeutic option for CML, and the Ad-SH2-HA-mediated killing strategy could be explored as a promising anti-leukemia agent in CML.

Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex.

PubMed

Schiering, N; Casale, E; Caccia, P; Giordano, P; Battistini, C

2000-11-07

Src homology 2 (SH2) domains are key modules in intracellular signal transduction. They link activated cell surface receptors to downstream targets by binding to phosphotyrosine-containing sequence motifs. The crystal structure of a Grb2-SH2 domain-phosphopeptide complex was determined at 2.4 A resolution. The asymmetric unit contains four polypeptide chains. There is an unexpected domain swap so that individual chains do not adopt a closed SH2 fold. Instead, reorganization of the EF loop leads to an open, nonglobular fold, which associates with an equivalent partner to generate an intertwined dimer. As in previously reported crystal structures of canonical Grb2-SH2 domain-peptide complexes, each of the four hybrid SH2 domains in the two domain-swapped dimers binds the phosphopeptide in a type I beta-turn conformation. This report is the first to describe domain swapping for an SH2 domain. While in vivo evidence of dimerization of Grb2 exists, our SH2 dimer is metastable and a physiological role of this new form of dimer formation remains to be demonstrated.

SH2/SH3 signaling proteins.

PubMed

Schlessinger, J

1994-02-01

SH2 and SH3 domains are small protein modules that mediate protein-protein interactions in signal transduction pathways that are activated by protein tyrosine kinases. SH2 domains bind to short phosphotyrosine-containing sequences in growth factor receptors and other phosphoproteins. SH3 domains bind to target proteins through sequences containing proline and hydrophobic amino acids. SH2 and SH3 domain containing proteins, such as Grb2 and phospholipase C gamma, utilize these modules in order to link receptor and cytoplasmic protein tyrosine kinases to the Ras signaling pathway and to phosphatidylinositol hydrolysis, respectively. The three-dimensional structures of several SH2 and SH3 domains have been determined by NMR and X-ray crystallography, and the molecular basis of their specificity is beginning to be unveiled.

The sub-energetic gamma-ray burst GRB 031203 as a cosmic analogue to the nearby GRB 980425.

PubMed

Soderberg, A M; Kulkarni, S R; Berger, E; Fox, D W; Sako, M; Frail, D A; Gal-Yam, A; Moon, D S; Cenko, S B; Yost, S A; Phillips, M M; Persson, S E; Freedman, W L; Wyatt, P; Jayawardhana, R; Paulson, D

2004-08-05

Over the six years since the discovery of the gamma-ray burst GRB 980425, which was associated with the nearby (distance approximately 40 Mpc) supernova 1998bw, astronomers have debated fiercely the nature of this event. Relative to bursts located at cosmological distance (redshift z approximately 1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed that the explosion was sub-energetic by a factor of 10. Here we report observations of the radio and X-ray afterglow of the recent GRB 031203 (refs 5-7), which has a redshift of z = 0.105. We demonstrate that it too is sub-energetic which, when taken together with the low gamma-ray luminosity, suggests that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. We expect intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRB 031203 and 980425) to reveal a large population of such events.

Expression, Refolding and Crystallizations of the Grb2-like (GADS) C-Terminal SH3 Domain Complexed with a SLP-76 Motif Peptide

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

Faravelli,A.; Dimasi, N.

The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain. GADS interacts through its C-terminal SH3 domain with the adaptor protein SLP-76, thus recruiting this protein and other associated molecules to the linker for activation of T-cell (LAT) protein. The DNA encoding the C-terminal SH3 domain of GADS (GADS-cSH3) was assembled synthetically using a recursive PCR technique and the protein was overexpressed in Escherichia coli, refolded and purified. Several crystals of this domain in complex with the SLP-76 peptide were obtained and characterized.

GRB 110731A within the IGC paradigm

NASA Astrophysics Data System (ADS)

Primorac, Daria; Ruffini, Remo; Pisani, Giovanni Battista; Aimuratov, Yerlan; Biancol, Carlo Luciano; Karlica, Mile; Melon Fuksman, Julio David; Moradi, Rahim; Muccino, Marco; Penacchioni, Ana Virginia; Rueda, Jorge Armando; Wang, Yu

2018-01-01

Bright gamma-ray burst (GRB) 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV) emission. We analyze these data within the induced gravitational collapse (IGC) paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN) assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep-GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = -1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

GRB 130427A: a nearby ordinary monster.

PubMed

Maselli, A; Melandri, A; Nava, L; Mundell, C G; Kawai, N; Campana, S; Covino, S; Cummings, J R; Cusumano, G; Evans, P A; Ghirlanda, G; Ghisellini, G; Guidorzi, C; Kobayashi, S; Kuin, P; La Parola, V; Mangano, V; Oates, S; Sakamoto, T; Serino, M; Virgili, F; Zhang, B-B; Barthelmy, S; Beardmore, A; Bernardini, M G; Bersier, D; Burrows, D; Calderone, G; Capalbi, M; Chiang, J; D'Avanzo, P; D'Elia, V; De Pasquale, M; Fugazza, D; Gehrels, N; Gomboc, A; Harrison, R; Hanayama, H; Japelj, J; Kennea, J; Kopac, D; Kouveliotou, C; Kuroda, D; Levan, A; Malesani, D; Marshall, F; Nousek, J; O'Brien, P; Osborne, J P; Pagani, C; Page, K L; Page, M; Perri, M; Pritchard, T; Romano, P; Saito, Y; Sbarufatti, B; Salvaterra, R; Steele, I; Tanvir, N; Vianello, G; Wiegand, B; Weigand, B; Wiersema, K; Yatsu, Y; Yoshii, T; Tagliaferri, G

2014-01-03

Long-duration gamma-ray bursts (GRBs) are an extremely rare outcome of the collapse of massive stars and are typically found in the distant universe. Because of its intrinsic luminosity (L ~ 3 × 10(53) ergs per second) and its relative proximity (z = 0.34), GRB 130427A reached the highest fluence observed in the γ-ray band. Here, we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-meter Liverpool and Faulkes telescopes, and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early universe and over the full range of GRB isotropic energies.

Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.

PubMed

He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J

2009-12-31

We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.

GRB 060614: a progress report

NASA Astrophysics Data System (ADS)

Caito, L.; Bernardini, M. G.; Bianco, C. L.; Dainotti, M. G.; Guida, R.; Ruffini, R.

2008-01-01

The explosion of GRB 060614, detected by the Swift satellite, produced a deep break in the GRB scenario opening new horizons of investigation, because it can't be traced back to any traditional scheme of classification. In fact, it manifests peculiarities both of long bursts and of short bursts. Above all, it is the first case of long duration near GRB without any bright Ib/c associated Supernova. We will show that, in our canonical GRB scenario ([l]), this ``anomalous'' situation finds a natural interpretation and allows us to discuss a possible variation to the traditional classification scheme, introducing the distinction between ``genuine'' and ``fake'' short bursts.

Strategies for Prompt Searches for GRB Afterglows: The Discovery of GRB 001011 Optical/Near-Infrared Counterpart Using Colour-Colour Selection

NASA Technical Reports Server (NTRS)

Gorosabel, J.; Fynbo, J. U.; Hjorth, J.; Wolf, C.; Andersen, M. I.; Pedersen, H.; Christensen, L.; Jensen, B. L.; Moller, P.; Afonso, J.;

GRB 130427A: A Nearby Ordinary Monster

NASA Technical Reports Server (NTRS)

Maselli, A.; Melandri, A.; Nava, L.; Mundell, C. G.; Kawai, N.; Campana, S.; Covino, S.; Cummings, J. R.; Cusumano, G.; Evans, P. A.;

Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl.

PubMed

Odai, H; Sasaki, K; Iwamatsu, A; Nakamoto, T; Ueno, H; Yamagata, T; Mitani, K; Yazaki, Y; Hirai, H

1997-04-15

Grb2/Ash and Shc are the adapter proteins that link tyrosine-kinase receptors to Ras and make tyrosine-kinase functionally associated with receptors and Ras in fibroblasts and hematopoietic cells. Grb2/Ash and Shc have the SH3, SH2, or phosphotyrosine binding domains. These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. However, there could remain unidentified signaling molecules that physically and functionally interact with these adapter proteins and have biologically important roles in the signaling pathways. By using the GST fusion protein including the full length of Grb2/Ash, we have found that c-Cbl and an unidentified 135-kD protein (pp135) are associated with Grb2/Ash. We have also found that they become tyrosine-phosphorylated by treatment of a human leukemia cell line, UT-7, with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have purified the pp135 by using GST-Grb2/Ash affinity column and have isolated the full-length complementary DNA (cDNA) encoding the pp135 using a cDNA probe, which was obtained by the degenerate polymerase chain reaction based on a peptide sequence of the purified pp135. The cloned cDNA has 3,958 nucleotides that contain a single long open reading frame of 3,567 nucleotides, encoding a 1,189 amino acid protein with a predicted molecular weight of approximately 133 kD. The deduced amino acid sequence reveals that pp135 is a protein that has one SH2, one SH3, and one proline-rich domain. The pp135, which contains two motifs conserved among the inositol polyphosphate-5-phosphatase proteins, was shown to have the inositol polyphosphate-5-phosphatase activity. The pp135 was revealed to associate constitutively with Grb2/Ash and inducibly with Shc using UT-7 cells stimulated with GM-CSF. In the cell lines derived from human chronic myelogenous leukemia, pp135 was constitutively tyrosine

DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed.

PubMed

Hitchins, Megan P; Bentley, Louise; Monk, David; Beechey, Colin; Peters, Jo; Kelsey, Gavin; Ishino, Fumitoshi; Preece, Michael A; Stanier, Philip; Moore, Gudrun E

2002-12-01

Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified within this region to date. GRB10 demonstrates an intricate tissue- and isoform-specific imprinting profile in humans, with paternal expression in fetal brain and maternal expression of one isoform in skeletal muscle. The mouse homolog is maternally transcribed. The GRB10 protein is a potent growth inhibitor and represents a candidate for SRS, which is characterized by pre- and postnatal growth retardation and a spectrum of additional dysmorphic features. Since imprinted genes tend to be grouped in clusters, we investigated the imprinting status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were found to replicate asynchronously, suggestive of imprinting, SNP expression analyses showed that neither gene was imprinted in multiple human fetal tissues. The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region. With the intent of using mouse Grb10 as an imprinted control, biallelic expression was consistently observed in fetal, postnatal, and adult brain of these mice, in contrast to the maternal-specific transcription previously demonstrated in brain in inter-specific F1 progeny. This may be a further example of over-expression of maternally derived transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted gene identified within 7p11.2-p13.

Panchromatic Observations of GRB 110205A and Other GRB Optical Prompt Observations Obtained by ROTSE

NASA Astrophysics Data System (ADS)

Zheng, Weikang; with a larger Collaboration

2011-09-01

The leading radiation mechanisms for gamma-ray bursts (GRBs), as predicted by the standard GRB fireball model, include synchrotron radiation, synchrotron self-Compton (SSC), and inverse Compton scattering from thermal photons. Panchromatic observations during GRB prompt emission are important to distinguish the mechanisms. GRB 110205A, triggered by Swift, is also detected by Suzaku, ROTSE-IIIb and BOOTES telescopes when the GRB is still radiating gamma-rays. These panchromatic observations, covering 6 orders of energy range from 1 eV to 5 MeV, will be presented. We clearly discover an interesting two-break energy spectrum for the first time, roughly consistent with the synchrotron spectrum predicted by the standard GRB fireball model. The two break energies can be explained as νc, the synchrotron cooling frequency, and νm, the synchrotron typical frequency. With a sample of GRBs with optical prompt detections from ROTSE observations, one can also constrain the self-absorption frequency, νa. These detailed prompt observations are important to discriminate different mechanisms and thus lead us to a better and deeper understanding of the GRB fireball model. This research is supported by the NASA grant NNX08AV63G and the NSF grant PHY-0801007.

DISCOVERY OF SN 2009nz ASSOCIATED WITH GRB 091127

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

Cobb, B. E.; Bloom, J. S.; Perley, D. A.

2010-08-01

We report SMARTS, Gemini, and Swift-UVOT observations of the optical transient (OT) associated with gamma-ray burst (GRB) 091127, at redshift 0.49, taken between 0.9 hr and 102 days following the Swift trigger. In our early-time observations, the OT fades in a manner consistent with previously observed GRB afterglows. However, after nine days post-burst, the OT is observed to brighten for a period of {approx}two weeks, after which the source resumes fading. A comparison of this late-time 'bump' to SN 1998bw (the broad-lined Type Ic supernova associated with GRB 980425), and several other GRB supernovae (SNe), indicates that the most straightforwardmore » explanation is that GRB 091127 was accompanied by a contemporaneous SN (SN 2009nz) that peaked at a magnitude of M{sub V} = -19.0 {+-} 0.2. SN 2009nz is globally similar to other GRB SNe, but evolves slightly faster than SN 1998bw and reaches a slightly dimmer peak magnitude. We also analyze the early-time UV-optical-IR spectral energy distribution of the afterglow of GRB 091127 and find that there is little to no reddening in the host galaxy along the line of sight to this burst.« less

Adapter molecule Grb2-associated binder 1 is specifically expressed in marginal zone B cells and negatively regulates thymus-independent antigen-2 responses.

PubMed

Itoh, Shousaku; Itoh, Motoyuki; Nishida, Keigo; Yamasaki, Satoru; Yoshida, Yuichi; Narimatsu, Masahiro; Park, Sung Joo; Hibi, Masahiko; Ishihara, Katsuhiko; Hirano, Toshio

2002-05-15

Grb2-associated binder 1 (Gab1) is a member of the Gab/daughter of sevenless family of adapter molecules involved in the signal transduction pathways of a variety of growth factors, cytokines, and Ag receptors. To know the role for Gab1 in hematopoiesis and immune responses in vivo, we analyzed radiation chimeras reconstituted with fetal liver (FL) cells of Gab1(-/-) mice, because Gab1(-/-) mice are lethal to embryos. Transfer of Gab1(-/-) FL cells of 14.5 days post-coitum rescued lethally irradiated mice, indicating that Gab1 is not essential for hematopoiesis. Although mature T and B cell subsets developed normally in the peripheral lymphoid organs, reduction of pre-B cells and increase of myeloid cells in the Gab1(-/-) FL chimeras suggested the regulatory roles for Gab1 in hematopoiesis. The chimera showed augmented IgM and IgG1 production to thymus-independent (TI)-2 Ag, although they showed normal responses for thymus-dependent and TI-1 Ags, indicating its negative role specific to TI-2 response. Gab1(-/-) splenic B cells stimulated with anti-delta-dextran plus IL-4 plus IL-5 showed augmented IgM and IgG1 production in vitro that was corrected by the retrovirus-mediated transfection of the wild-type Gab1 gene, clearly demonstrating the cell-autonomous, negative role of Gab1. Furthermore, we showed that the negative role of Gab1 required its Src homology 2-containing tyrosine phosphatase-2 binding sites. Cell fractionation analysis revealed that nonfollicular B cells were responsible for the augmented Ab production in vitro. Consistent with these results, the Gab1 gene was expressed in marginal zone B cells but not follicular B cells. These results indicated that Gab1 is a unique negative regulator specific for TI-2 responses.

The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B.

PubMed

Lapinski, Philip E; Oliver, Jennifer A; Bodie, Jennifer N; Marti, Francesc; King, Philip D

2009-11-01

Adapter proteins play key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules. In T lymphocytes, the role of several different types of adapter proteins in T-cell antigen receptor signal transduction is well established. An exception to this is the family of T-cell-specific adapter (TSAd) proteins comprising of TSAd, adapter protein of unknown function (ALX), SH2D4A, and SH2D4B. Only recently has the function of these adapters in T-cell signal transduction been explored. Here, we discuss advances in our understanding of the role of this family of adapter proteins in T cells. Their function as regulators of signal transduction in other cell types is also discussed.

Signaling by ectopically expressed Drosophila Src64 requires the protein-tyrosine phosphatase corkscrew and the adapter downstream of receptor kinases.

PubMed

Cooper, J A; Simon, M A; Kussick, S J

1996-11-01

Vertebrate Src can be activated by specific mutations to become oncogenic. Analogous mutations in Drosophila Src64 (DSrc) induce abnormal differentiation of photoreceptor cells when expressed ectopically in the developing Drosophila adult eye. We have investigated the roles that the adapter protein, Downstream of receptor kinases (Drk), and the SH2 domain-containing tyrosine phosphatase, Corkscrew (Csw), play in this process. We find that dominant-negative mutations in either the drk or csw genes ameliorate the developmental abnormalities induced by activated DSrc. This suggests that Drk and Csw are required downstream of, or parallel to, DSrc. Csw does not act solely as an upstream activator of DSrc. The results are discussed in relation to potential roles for the vertebrate homologues of Drk and Csw (Grb2 and SHP2, respectively) in the transformation of fibroblasts by vertebrate Src.

Ubiquitin ligase Nedd4-2 modulates Kv1.3 current amplitude and ion channel protein targeting

PubMed Central

Velez, Patricio; Schwartz, Austin B.; Iyer, Subashini R.; Warrington, Anthony

2016-01-01

Voltage-dependent potassium channels (Kv) go beyond the stabilization of the resting potential and regulate biochemical pathways, regulate intracellular signaling, and detect energy homeostasis. Because targeted deletion and pharmacological block of the Kv1.3 channel protein produce marked changes in metabolism, resistance to diet-induced obesity, and changes in olfactory structure and function, this investigation explored Nedd4-2-mediated ubiquitination and degradation to regulate Kv1.3 channel density. Heterologous coexpression of Nedd4-2 ligase and Kv1.3 in HEK 293 cells reduced Kv1.3 current density without modulation of kinetic properties as measured by patch-clamp electrophysiology. Modulation of current density was dependent on ligase activity and was lost through point mutation of cysteine 938 in the catalytic site of the ligase (Nedd4-2CS). Incorporation of adaptor protein Grb10 relieved Nedd4-2-induced current suppression as did application of the proteasome inhibitor Mg-132. SDS-PAGE and immunoprecipitation strategies demonstrated a channel/adaptor/ligase signalplex. Pixel immunodensity was reduced for Kv1.3 in the presence of Nedd4-2, which was eliminated upon additional incorporation of Grb10. We confirmed Nedd4-2/Grb10 coimmunoprecipitation and observed an increased immunodensity for Nedd4-2 in the presence of Kv1.3 plus Grb10, regardless of whether the catalytic site was active. Kv1.3/Nedd4-2 were reciprocally coimmunoprecipated, whereby mutation of the COOH-terminal, SH3-recognition (493–498), or ubiquitination sites on Kv1.3 (lysines 467, 476, 498) retained coimmunoprecipitation, while the latter prevented the reduction in channel density. A model is presented for which an atypical interaction outside the canonical PY motif may permit channel/ligase interaction to lead to protein degradation and reduced current density, which can involve Nedd4-2/Grb10 interactions to disrupt Kv1.3 loss of current density. PMID:27146988

Distinct Recruitment and Function of Gab1 and Gab2 in Met Receptor-mediated Epithelial Morphogenesis

PubMed Central

Lock, Lisa S.; Maroun, Christiane R.; Naujokas, Monica A.; Park, Morag

2002-01-01

The Gab family of docking proteins (Gab1 and Gab2) are phosphorylated in response to various cytokines and growth factors. Gab1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis. To determine whether Gab1 and Gab2 are functionally redundant, we have examined the role of Gab2 in epithelial cells. Both Gab1 and Gab2 are expressed in epithelial cells and localize to cell-cell junctions. However, whereas overexpression of Gab1 promotes a morphogenic response, the overexpression of Gab2 fails to induce this response. We show that Gab2 recruitment to the Met receptor is dependent on the Grb2 adapter protein. In contrast, Gab1 recruitment to Met is both Grb2 dependent and Grb2 independent. The latter requires a novel amino acid sequence present in the Met-binding domain of Gab1 but not Gab2. Mutation of these residues in Gab1 impairs both association with the Met receptor and the ability of Gab1 to promote a morphogenic response, whereas their insertion into Gab2 increases Gab2 association with Met, but does not confer on Gab2 the ability to promote epithelial morphogenesis. We propose that the Grb2-independent recruitment of Gab proteins to Met is necessary but not sufficient to promote epithelial morphogenesis. PMID:12058075

GRB 011121: A Collimated Outflow into Wind-Blown Surroundings

NASA Technical Reports Server (NTRS)

Greiner, J.; Klose, S.; Salvato, M.; Zeh, A.; Schwarz, R.; Hartmann, D. H.; Masetti, N.; Stecklum, B.; Lamer, G.; Lodieu, N.;

GRB 021211 as a Faint Analogue of GRB 990123: Exploring the Similarities and Differences in the Optical Afterglows

NASA Technical Reports Server (NTRS)

Holland, Stephen T.; Bersier, David; Bloom, J. S.; Garnavich, Peter M.; Caldwell, Nelson; Challis, Peter; Kirshner, Robert; Luhman, Kevin; McLeod, Brian; Stanek, K. Z.

2004-01-01

We present BVR(sub c)JHK(sub s) photometry of the optical afterglow of the gamma-ray burst GRB 021211 taken at the Magellan, MMT, and WIYN observatories between 0.7 and 50 days after the burst. We find an intrinsic spectral slope at optical and near-infrared wavelengths of 0.69 +/- 0.14 at 0.87 days. The optical decay during the first day is almost identical to that of GRB 990123 except that GRB 021211's optical afterglow was intrinsically approximately 38 times fainter and the transition from the reverse shock to the forward shock may have occurred earlier than it did for GRB 990123. We find no evidence for a jet break or the cooling break passing through optical frequencies during the first day after the burst. There is weak evidence for a break in the J-band decay between 0.89 and 1.87 days which may be due to a jet. The optical and infrared data are consistent with a relativistic fireball where the shocked electrons are in the slow cooling regime and the electron index is 2.3 +/- 0.1. The burst appears to have occurred in a homogeneous ambient medium. Our analysis suggests that the jet of GRB 021211 may have a small opening angle (1.4 deg-4.4 deg) and that the total gamma-ray energy is much less than the canonical value of 1.33 x 10(exp 51) erg. If, this is the case then most of the energy of the burst may be in another form such as a frozen magnetic field, in supernova ejecta, or in a second jet component. The host galaxy of GRB 021211 is subluminous and has a star formation rate of at least 1 solar mass/yr.

Interactive roles of Ras, insulin receptor substrate-1, and proteins with Src homology-2 domains in insulin signaling in Xenopus oocytes.

PubMed

Chuang, L M; Hausdorff, S F; Myers, M G; White, M F; Birnbaum, M J; Kahn, C R

1994-11-04

Insulin receptor substrate-1 (IRS-1) serves as the major immediate substrate of insulin/insulin-like growth factor (IGF)-1 receptors and following tyrosine phosphorylation binds to specific Src homology-2 (SH2) domain-containing proteins including the p85 subunit of phosphatidylinositol (PI) 3-kinase and GRB2, a molecule believed to link IRS-1 to the Ras pathway. To investigate how these SH2-containing signaling molecules interact to regulate insulin/IGF-1 action, IRS-1, glutathione S-transferase (GST)-SH2 domain fusion proteins and Ras proteins were microinjected into Xenopus oocytes. We found that pleiotropic insulin actions are mediated by IRS-1 through two independent, but convergent, pathways involving PI 3-kinase and GRB2. Thus, microinjection of GST-fusion proteins of either p85 or GRB2 inhibited IRS-1-dependent activation of mitogen-activated protein (MAP) and S6 kinases and oocyte maturation, although only the GST-SH2 of p85 reduced insulin-stimulated PI 3-kinase activation. Co-injection of a dominant negative Ras (S17N) with IRS-1 inhibited insulin-stimulated MAP and S6 kinase activation. Micro-injection of activated [Arg12,Thr59]Ras increased basal MAP and S6 kinase activities and sensitized the oocytes to insulin-stimulated maturation without altering insulin-stimulated PI 3-kinase. The Ras-enhanced oocyte maturation response, but not the elevated basal level of MAP and S6 kinase, was partially blocked by the SH2-p85, but not SH2-GRB2. These data strongly suggest that IRS-1 can mediate many of insulin's actions on cellular enzyme activation and cell cycle progression requires binding and activation of multiple different SH2-domain proteins.

THE PROPERTIES OF THE 2175 A EXTINCTION FEATURE DISCOVERED IN GRB AFTERGLOWS

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

Zafar, Tayyaba; Watson, Darach; Eliasdottir, Ardis

The unequivocal, spectroscopic detection of the 2175 A bump in extinction curves outside the Local Group is rare. To date, the properties of the bump have been examined in only two gamma-ray burst (GRB) afterglows (GRB 070802 and GRB 080607). In this work, we analyze in detail the detections of the 2175 Angstrom-Sign extinction bump in the optical spectra of two further GRB afterglows: GRB 080605 and 080805. We gather all available optical/near-infrared photometric, spectroscopic, and X-ray data to construct multi-epoch spectral energy distributions (SEDs) for both GRB afterglows. We fit the SEDs with the Fitzpatrick and Massa model withmore » a single or broken power law. We also fit a sample of 38 GRB afterglows, known to prefer a Small Magellanic Cloud (SMC)-type extinction curve, with the same model. We find that the SEDs of GRB 080605 and GRB 080805 at two epochs are fit well with a single power law with a derived extinction of A{sub V} = 0.52{sup +0.13}{sub -0.16} and 0.50{sup +0.13}{sub -0.10}, and 2.1{sup +0.7}{sub -0.6} and 1.5 {+-} 0.2, respectively. While the slope of the extinction curve of GRB 080805 is not well constrained, the extinction curve of GRB 080605 has an unusual very steep far-UV rise together with the 2175 A bump. Such an extinction curve has previously been found in only a small handful of sightlines in the Milky Way. One possible explanation of such an extinction curve may be dust arising from two different regions with two separate grain populations, however we cannot distinguish the origin of the curve. We finally compare the four 2175 A bump sightlines to the larger GRB afterglow sample and to Local Group sightlines. We find that while the width and central positions of the bumps are consistent with what is observed in the Local Group, the relative strength of the detected bump (A{sub bump}) for GRB afterglows is weaker for a given A{sub V} than for almost any Local Group sightline. Such dilution of the bump strength may offer

Photometric and Spectroscopic Observations of GRB 140629A

NASA Astrophysics Data System (ADS)

Xin, Li-Ping; Zhong, Shu-Qing; Liang, En-Wei; Wang, Jing; Liu, Hao; Zhang, Tian-Meng; Huang, Xiao-Li; Li, Hua-Li; Qiu, Yu-Lei; Han, Xu-Hui; Wei, Jian-Yan

2018-06-01

We present our optical photometric and spectroscopical observations of GRB 140629A. A redshift of z = 2.275 ±0.043 is measured through the metal absorption lines in our spectroscopic data. Using our photometric data and multiple observational data from other telescopes, we show that its optical light curve is well interpreted with the standard forward shock models in the thin shell case. Its optical–X-ray afterglow spectrum is jointly fitted with a single power-law function, yielding a photon index of ‑1.90 ± 0.05. The optical extinction and neutral hydrogen absorption of the gamma-ray burst (GRB) host galaxy are negligible. The fit to the light curve with the standard models shows that the ambient density is 60 ± 9 cm‑3 and the GRB radiating efficiency is as low as ∼0.24%, likely indicating a baryonic-dominated ejecta of this GRB. This burst agrees well with the {L}{{p},{iso}}{--}{E}p{\\prime }{--}{{{Γ }}}0 relation, but confidently violates those empirical relations involving geometric corrections (or jet break time). This gives rise to an issue of the possible selection effect on these relations since the jet opening angle of this GRB is extremely narrow (0.04 rad).

Co-clustering of Fcgamma and B cell receptors induces dephosphorylation of the Grb2-associated binder 1 docking protein.

PubMed

Koncz, G; Tóth, G K; Bökönyi, G; Kéri, G; Pecht, I; Medgyesi, D; Gergely, J; Sármay, G

2001-07-01

The immunoreceptor tyrosine-based inhibitory motif (ITIM) of human type IIb Fcgamma receptor (FcgammaRIIb) is phosphorylated on its tyrosine upon co-clustering with the B cell receptor (BCR). The phosphorylated ITIM (p-ITIM) binds to the SH2 domains of polyphosphoinositol 5-phosphatase (SHIP) and the tyrosine phosphatase, SHP-2. We investigated the involvement of the molecular complex composed of the phosphorylated SHIP and FcgammaRIIb in the activation of SHP-2. As a model compound, we synthesized a bisphosphopeptide, combining the sequences of p-ITIM and the N-terminal tyrosine phosphorylated motif of SHIP with a flexible spacer. This compound bound to the recombinant SH2 domains of SHP-2 with high affinity and activated the phosphatase in an in vitro assay. These data suggest that the phosphorylated FcgammaRII-SHIP complexes formed in the intact cells may also activate SHP-2. Grb2-associated binder 1 (Gab1) is a multisite docking protein, which becomes tyrosine-phosphorylated in response to various types of signaling, including BCR. In turn it binds to the SH2 domains of SHP-2, SHIP and the p85 subunit of phosphatidyl inositol 3-kinase (PtdIns3-K) and may regulate their activity. Gab1 is a potential substrate of SHP-2, thus its binding to FcgammaRIIb may modify the Gab1-bound signaling complex. We show here that Gab1 is part of the multiprotein complex assembled by FcgammaRIIb upon its co-clustering with BCR. Gab1 may recruit SH2 domain-containing molecules to the phosphorylated FcgammaRIIb. SHP-2, activated upon the binding to FcgammaRIIb-SHIP complex, partially dephosphorylates Gab1, resulting in the release of PtdIns3-K and ultimately in the inhibition of downstream activation pathways in BCR/FcgammaRIIb co-aggregated cells.

Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer.

PubMed

Sparano, Joseph A; Goldstein, Lori J; Childs, Barrett H; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L; Bugarini, Roberto; Rowley, Steve; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Kenny, Paraic A; Sledge, George W; Gray, Robert

2011-11-15

To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins*

PubMed Central

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-01

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. PMID:27927989

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.

PubMed

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-20

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Understanding Grb Physics With Multi-Wavelength Data

NASA Astrophysics Data System (ADS)

Zhang, Bing

The study of Gamma-ray bursts (GRBs) has entered a full multi-wavelength era. A rich trove of data from NASA GRB missions and ground-based follow up observations have been collected. Careful data mining with well-defined scientific objectives holds the key to address open questions in GRB physics, such as jet composition, radiation mechanism, progenitor and central engine physics. We propose to perform data analyses in the following three directions. 1. The time resolved GRB spectra have a dominant component that can be fit with a phenomenological ``Band'' function. The physical meaning of this function remains unclear. Recently we made a breakthrough in theoretical modeling, and showed that fast-cooling synchrotron radiation of electrons in a decreasing magnetic field can mimic the Band function in detector's bandpass, but differs from Band function slightly. We propose to apply this physically-motivated model to systematically fit the GRB prompt emission data collected by Fermi GBM and LAT, and test whether the dominant GRB emission mechanism is fast cooling synchrotron radiation. We will also fit time-dependent spectra with a time-dependent model to investigate whether a quasi- thermal "photosphere'' emission component is indeed needed to fit the observed spectra. This would shed light onto the unknown composition of GRB jets. By fitting the time resolved spectra, we will also constrain important physical parameters of GRB prompt emission, such as the emission site of GRBs, the strength of magnetic fields, as well as their evolution with radius. 2. Recent GRB multi-wavelength observations suggest that it is not straightforward to define the physical category of a GRB based on the traditional classification in the "duration''-"hardness'' domain. Some long-duration GRBs may not have a massive star origin, while some short-duration GRBs may instead have a massive star origin. We propose to systematically study the gamma-ray Swift/BAT, Fermi/GBM- LAT), X-ray (Swift

SYNCHROTRON ORIGIN OF THE TYPICAL GRB BAND FUNCTION—A CASE STUDY OF GRB 130606B

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

Zhang, Bin-Bin; Briggs, Michael S.; Uhm, Z. Lucas

2016-01-10

We perform a time-resolved spectral analysis of GRB 130606B within the framework of a fast-cooling synchrotron radiation model with magnetic field strength in the emission region decaying with time, as proposed by Uhm and Zhang. The data from all time intervals can be successfully fit by the model. The same data can be equally well fit by the empirical Band function with typical parameter values. Our results, which involve only minimal physical assumptions, offer one natural solution to the origin of the observed GRB spectra and imply that, at least some, if not all, Band-like GRB spectra with typical Bandmore » parameter values can indeed be explained by synchrotron radiation.« less

A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation.

PubMed

Dikic, I; Tokiwa, G; Lev, S; Courtneidge, S A; Schlessinger, J

1996-10-10

The mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. Transient overexpression of a dominant interfering mutant of Pyk2 or the protein tyrosine kinase Csk reduces LPA- or bradykinin-induced activation of MAP kinase. LPA- or bradykinin-induced MAP kinase activation was also inhibited by overexpression of dominant interfering mutants of Grb2 and Sos. We propose that Pyk2 acts with Src to link Gi- and Gq-coupled receptors with Grb2 and Sos to activate the MAP kinase signalling pathway in PC12 cells.

Optical study of the counterpart to GRB 990712

NASA Astrophysics Data System (ADS)

Gorosabel, J.; Castro-Tirado, A. J.; Saizar, P.; Rattenbury, N. J.; Bond, I. A.; Yock, P.; Hearnshaw, J.; Kilmartin, P. M.; Muraki, Y.; Nakamura, T.; Ohnishi, K.; Reid, M.; Saito, To; Noda, S.

2000-09-01

Quasi-simultaneous BVR-band observations performed from New Zealand and Argentina ~16 hr after the burst clearly detected the optical counterpart to GR-B 990712. Based on these measurements we construct the optical multi-band spectrum. We report that the spectrum between the R and B bands follows a power law Fv~νβ with index β=-0.50+/-0.16. The spectrum is consistent with a stretch of an afterglow spectrum between the peak frequency, νm, and the cooling break, νc. The photon index derived following the model of Sari et al. (1998), p=2.36+/-0.08 is compatible with β and the power law decay, α, only if no absorption is introduced. Thus, our results support that GRB 990712 occurred in a low density region, resembling GRB 970508. .

TGF-β2 induces Grb2 to recruit PI3-K to TGF-RII that activates JNK/AP-1-signaling and augments invasiveness of Theileria-transformed macrophages

PubMed Central

Haidar, Malak; Whitworth, Jessie; Noé, Gaelle; Liu, Wang Qing; Vidal, Michel; Langsley, Gordon

2015-01-01

Theileria-infected macrophages display many features of cancer cells such as heightened invasive capacity; however, the tumor-like phenotype is reversible by killing the parasite. Moreover, virulent macrophages can be attenuated by multiple in vitro passages and so provide a powerful model to elucidate mechanisms related to transformed macrophage virulence. Here, we demonstrate that in two independent Theileria-transformed macrophage cell lines Grb2 expression is down-regulated concomitant with loss of tumor virulence. Using peptidimer-c to ablate SH2 and SH3 interactions of Grb2 we identify TGF-receptor II and the p85 subunit of PI3-K, as Grb2 partners in virulent macrophages. Ablation of Grb2 interactions reduces PI3-K recruitment to TGF-RII and decreases PIP3 production, and dampens JNK phosphorylation and AP-1-driven transcriptional activity down to levels characteristic of attenuated macrophages. Loss of TGF-R>PI3-K>JNK>AP-1 signaling negatively impacts on virulence traits such as reduced JAM-L/ITG4A and Fos-B/MMP9 expression that contribute to virulent macrophage adhesion and invasiveness. PMID:26511382

A Bulk Comptonization Model for the Prompt GRB Emission and its Relation to the Fermi GRB Spectra

NASA Technical Reports Server (NTRS)

Kazanas, Demosthenes

2010-01-01

We present a model in which the GRB prompt emission at E E(sub peak) is due to bulk Comptonization by the relativistic blast wave motion of either its own synchrotron photons of ambient photons of the stellar configuration that gave birth to the GRB. The bulk Comptonization process then induces the production of relativistic electrons of Lorentz factor equal to that of the blast wave through interactions with its ambient protons. The inverse compton emission of these electrons produces a power law component that extends to multi GeV energies in good agreement with the LAT GRB observations.

Radio observations of GRB 100418a: Test of an energy injection model explaining long-lasting GRB afterglows

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

Moin, A.; Wang, Z.; Chandra, P.

We present the results of our radio observational campaign of gamma-ray burst (GRB) 100418a, for which we used the Australia Telescope Compact Array, the Very Large Array, and the Very Long Baseline Array. GRB 100418a was a peculiar GRB with unusual X-ray and optical afterglow profiles featuring a plateau phase with a very shallow rise. This observed plateau phase was believed to be due to a continued energy injection mechanism that powered the forward shock, giving rise to an unusual and long-lasting afterglow. The radio afterglow of GRB 100418a was detectable several weeks after the prompt emission. We conducted long-termmore » monitoring observations of the afterglow and attempted to test the energy injection model advocating that the continuous energy injection is due to shells of material moving at a wide range of Lorentz factors. We obtained an upper limit of γ < 7 for the expansion rate of the GRB 100418a radio afterglow, indicating that the range-of-Lorentz factor model could only be applicable for relatively slow-moving ejecta. A preferred explanation could be that continued activity of the central engine may have powered the long-lasting afterglow.« less

THE EXTREMELY RED HOST GALAXY OF GRB 080207

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

Hunt, Leslie; Cresci, Giovanni; Palazzi, Eliana

2011-08-01

We present optical, near-infrared, and Spitzer IRAC and MIPS observations of the host galaxy of the dark Swift gamma-ray burst GRB 080207. The host is faint, with extremely red optical-infrared colors (R - K = 6.3, 24 {mu}m/R-band flux {approx}1000) making it an extremely red object (ERO) and a dust-obscured galaxy (DOG). The spectral energy distribution (SED) shows the clear signature of the 1.6 {mu}m photometric 'bump', typical of evolved stellar populations. We use this bump to establish the photometric redshift z{sub phot} as 2.2{sup +0.2}{sub -0.3}, using a vast library of SED templates, including M 82. The star formationmore » rate (SFR) inferred from the SED fitting is {approx}119 M{sub sun} yr{sup -1}, the stellar mass 3 x 10{sup 11} M{sub sun}, and A{sub V} extinction from 1 to 2 mag. The ERO and DOG nature of the host galaxy of the dark GRB 080207 may be emblematic of a distinct class of dark GRB hosts, with high SFRs, evolved and metal-rich stellar populations, and significant dust extinction within the host galaxy.« less

GRB 060614: a Fake Short Gamma-Ray Burst

NASA Astrophysics Data System (ADS)

Caito, L.; Bernardini, M. G.; Bianco, C. L.; Dainotti, M. G.; Guida, R.; Ruffini, R.

2008-05-01

The explosion of GRB 060614 produced a deep break in the GRB scenario and opened new horizons of investigation because it can't be traced back to any traditional scheme of classification. In fact, it has features both of long bursts and of short bursts and, above all, it is the first case of long duration near GRB without any bright Ib/c associated Supernova. We will show that, in our canonical GRB scenario [1], this ``anomalous'' situation finds a natural interpretation and allows us to discuss a possible variation to the traditional classification scheme, introducing the distinction between ``genuine'' and ``fake'' short bursts.

The high-redshift gamma-ray burst GRB 140515A

DOE PAGES

Melandri, A.; Bernardini, M. G.; D'Avanzo, P. D.; ...

2015-09-09

High-redshift gamma-ray bursts (GRBs) offer several advantages when studying the distant Universe, providing unique information about the structure and properties of the galaxies in which they exploded. Spectroscopic identification with large ground-based telescopes has improved our knowledge of this kind of distant events. We present the multi-wavelength analysis of the high-zSwift GRB GRB 140515A (z = 6.327). The best estimate of the neutral hydrogen fraction of the intergalactic medium towards the burst is x HI ≤ 0.002. The spectral absorption lines detected for this event are the weakest lines ever observed in GRB afterglows, suggesting that GRB 140515A exploded inmore » a very low-density environment. Its circum-burst medium is characterised by an average extinction (AV ~ 0.1) that seems to be typical of z ≥ 6 events. The observed multi-band light curves are explained either with a very hard injected spectrum (p = 1.7) or with a multi-component emission (p = 2.1). In the second case a long-lasting central engine activity is needed in order to explain the late time X-ray emission. Furthermore, the possible origin of GRB 140515A in a Pop III (or in a Pop II star with a local environment enriched by Pop III) massive star is unlikely.« less

MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

PubMed

Shelby, Shameka J; Colwill, Karen; Dhe-Paganon, Sirano; Pawson, Tony; Thompson, Debra A

2013-01-01

The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

The VLT/X-shooter GRB afterglow legacy survey

NASA Astrophysics Data System (ADS)

Kaper, Lex; Fynbo, Johan P. U.; Pugliese, Vanna; van Rest, Daan

2017-11-01

The Swift satellite allows us to use gamma-ray bursts (GRBs) to peer through the hearts of star forming galaxies through cosmic time. Our open collaboration, representing most of the active European researchers in this field, builds a public legacy sample of GRB X-shooter spectroscopy while Swift continues to fly. To date, our spectroscopy of more than 100 GRB afterglows covers a redshift range from 0.059 to about 8 (Tanvir et al. 2009, Nature 461, 1254), with more than 20 robust afterglow-based metallicity measurements (over a redshift range from 1.7 to 5.9). With afterglow spectroscopy (throughout the electromagnetic spectrum from X-rays to the sub-mm) we can hence characterize the properties of star-forming galaxies over cosmic history in terms of redshift, metallicity, molecular content, ISM temperature, UV-flux density, etc.. These observations provide key information on the final evolution of the most massive stars collapsing into black holes, with the potential of probing the epoch of the formation of the first (very massive) stars. VLT/X-shooter (Vernet et al. 2011, A&A 536, A105) is in many ways the ideal GRB follow-up instrument and indeed GRB follow-up was one of the primary science cases behind the instrument design and implementation. Due to the wide wavelength coverage of X-shooter, in the same observation one can detect molecular H2 absorption near the atmospheric cut-off and many strong emission lines from the host galaxy in the near-infrared (e.g., Friis et al. 2015, MNRAS 451, 167). For example, we have measured a metallicity of 0.1 Z ⊙ for GRB 100219A at z = 4.67 (Thöne et al. 2013, MNRAS 428, 3590), 0.02 Z ⊙ for GRB 111008A at z = 4.99 (Sparre et al. 2014, ApJ 785, 150) and 0.05 Z ⊙ for GRB 130606A at z = 5.91 (Hartoog et al. 2015, A&A 580, 139). In the latter, the very high value of [Al/Fe]=2.40 +/- 0.78 might be due to a proton capture process and may be a signature of a previous generation of massive (perhaps even the first) stars

The extraordinarily bright optical afterglow of GRB 991208 and its host galaxy

NASA Astrophysics Data System (ADS)

Castro-Tirado, A. J.; Sokolov, V. V.; Gorosabel, J.; Castro Cerón, J. M.; Greiner, J.; Wijers, R. A. M. J.; Jensen, B. L.; Hjorth, J.; Toft, S.; Pedersen, H.; Palazzi, E.; Pian, E.; Masetti, N.; Sagar, R.; Mohan, V.; Pandey, A. K.; Pandey, S. B.; Dodonov, S. N.; Fatkhullin, T. A.; Afanasiev, V. L.; Komarova, V. N.; Moiseev, A. V.; Hudec, R.; Simon, V.; Vreeswijk, P.; Rol, E.; Klose, S.; Stecklum, B.; Zapatero-Osorio, M. R.; Caon, N.; Blake, C.; Wall, J.; Heinlein, D.; Henden, A.; Benetti, S.; Magazzù, A.; Ghinassi, F.; Tommasi, L.; Bremer, M.; Kouveliotou, C.; Guziy, S.; Shlyapnikov, A.; Hopp, U.; Feulner, G.; Dreizler, S.; Hartmann, D.; Boehnhardt, H.; Paredes, J. M.; Martí, J.; Xanthopoulos, E.; Kristen, H. E.; Smoker, J.; Hurley, K.

2001-05-01

Broad-band optical observations of the extraordinarily bright optical afterglow of the intense gamma-ray burst GRB 991208 started ~2.1 days after the event and continued until 4 Apr. 2000. The flux decay constant of the optical afterglow in the R-band is -2.30 +/- 0.07 up to ~5 days, which is very likely due to the jet effect, and it is followed by a much steeper decay with constant -3.2 +/- 0.2, the fastest one ever seen in a GRB optical afterglow. A negative detection in several all-sky films taken simultaneously with the event, that otherwise would have reached naked eye brightness, implies either a previous additional break prior to ~2 days after the occurrence of the GRB (as expected from the jet effect) or a maximum, as observed in GRB 970508. The existence of a second break might indicate a steepening in the electron spectrum or the superposition of two events, resembling GRB 000301C. Once the afterglow emission vanished, contribution of a bright underlying supernova was found on the basis of the late-time R-band measurements, but the light curve is not sufficiently well sampled to rule out a dust echo explanation. Our redshift determination of z = 0.706 indicates that GRB 991208 is at 3.7 Gpc (for Ho = 60 km s-1 Mpc-1, OMEGAo = 1 and LAMDAo = 0), implying an isotropic energy release of 1.15 x 1053 erg which may be relaxed by beaming by a factor >102. Precise astrometry indicates that the GRB coincides within 0.2" with the host galaxy, thus supporting a massive star origin. The absolute magnitude of the galaxy is MB = -18.2, well below the knee of the galaxy luminosity function and we derive a star-forming rate of (11.5 +/- 7.1) Msun yr-1, which is much larger than the present-day rate in our Galaxy. The quasi-simultaneous broad-band photometric spectral energy distribution of the afterglow was determined ~3.5 day after the burst (Dec. 12.0) implying a cooling frequency nuc below the optical band, i.e. supporting a jet model with p = -2.30 as the index of

Pi of the Sky observation of GRB160625B

NASA Astrophysics Data System (ADS)

Opiela, Rafał; Batsch, Tadeusz; Castro-Tirado, Alberto Javier; Czyrkowski, Henryk; Ćwiek, Arkadiusz; Ćwiok, Mikołaj; DÄ browski, Ryszard; Jelinek, Martin; Kasprowicz, Grzegorz; Majcher, Ariel; Małek, Katarzyna; Mankiewicz, Lech; Nawrocki, Krzysztof; Obara, Łukasz; Piotrowski, Lech; Siudek, Małgorzata; Sokołowski, Marcin; Wawrzaszek, Roman; Wrochna, Grzegorz; Zaremba, Marcin; Żarnecki, Aleksander Filip

2017-08-01

Pi of the Sky is a system of wide field of view robotic telescopes, which search for short timescale astrophysical phenomena, especially for prompt optical GRB emission. The system was designed for autonomous operation, monitoring a large fraction of the sky to a depth of 12m-13m and with time resolution of the order of 10 seconds. Custom designed CCD cameras are equipped with Canon lenses f = 85 mm, f/d = 1.2 and cover 20° × 20° of the sky each. The final system with 16 cameras on 4 equatorial mounts was completed in 2014 at the INTA El Arenosillo Test Centre in Spain. GRB160625B was an extremely bright GRB with three distinct emission episodes. Cameras of the Pi of the Sky observatory in Spain were not observing the position of the GRB160625B prior to the first emission episode. Observations started only after receiving Fermi/GBM trigger, about 140 seconds prior to the second emission. As the position estimate taken from the Fermi alert and used to position the telescope was not very accurate, the actual position of the burst happened to be in the overlap region of two cameras, resulting in two independent sets of measurements. Light curves from both cameras were reconstructed using the Luiza framework. No object brighter than 12.4m (3σ limit) was observed prior to the second GRB emission. An optical flash was identified on an image starting -5.9s before the time of the Fermi/LAT trigger, brightening to about 8m on the next image and then becoming gradually dimmer, fading below our sensitivity after about 400s. Emission features as measured in different spectral bands indicate that the three emission episodes of GRB160625B were dominated by distinct physics process. Simultaneously observations in gamma-rays and optical wavelengths support the hypothesis that this was the first observed transition from thermal to non-thermal radiation in a single GRB. Main results of the combined analysis are presented.

The absence of Grb2-associated binder 2 (Gab2) does not disrupt NK cell development and functions.

PubMed

Zompi, Simona; Gu, Hahiua; Colucci, Francesco

2004-10-01

Scaffolding molecules bind simultaneously and link together various components of signal-transduction pathways. Grb2-associated binder 2 (Gab2) is a scaffolding protein required for FcgammaR-initiated allergic responses in mast cells and FcgammaR-mediated phagocytosis in macrophages, where it links IgE and IgG receptors to the phosphatidylinositol-3 kinase (PI-3K) pathway. The FcgammaR expressed by natural killer (NK) cells triggers antibody-dependent cellular cytotoxicity (ADCC). We show here that mouse NK cells express Gab2 and that although PI-3K was required for ADCC, this FcgammaR-mediated function was normal in Gab2-/- NK cells. Moreover, NK cell development, spontaneous cytotoxicity, and responses to and production of cytokines were not perturbed in Gab2-/- mice. Considering the striking differences between the signaling requirements of FcgammaR in macrophages and NK cells, our findings suggest that the organization of signal transduction downstream of the same FcR can be cell type-specific. Conversely, Gab family members Gab1, Gab2, and Gab3 may play specific roles in different leukocytes. As pharmacological targeting of Gab2 in mast cells is a potential strategy to treat allergy, our results suggest prudence, as NK cells may participate in IgE-mediated anaphylaxis in a Gab2-independent manner.

Besides an ITIM/SHP-1-dependent pathway, CD22 collaborates with Grb2 and plasma membrane calcium-ATPase in an ITIM/SHP-1-independent pathway of attenuation of Ca2+i signal in B cells

PubMed Central

Chen, Jie; Wang, Hong; Xu, Wei-Ping; Wei, Si-Si; Li, Hui Joyce; Mei, Yun-Qing; Li, Yi-Gang; Wang, Yue-Peng

2016-01-01

CD22 is a surface immunoglobulin implicated in negative regulation of B cell receptor (BCR) signaling; particularly inhibiting intracellular Ca2+ (Ca2+i)signals. Its cytoplasmic tail contains six tyrosine residues (Y773/Y783/Y817/Y828/Y843/Y863, designated Y1~Y6 respectively), including three (Y2/5/6) lying within immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that serve to recruit the protein tyrosine phosphatase SHP-1 after BCR activation-induced phosphorylation. The mechanism of inhibiting Ca2+i by CD22 has been poorly understood. Previous study demonstrated that CD22 associated with plasma membrane calcium-ATPase (PMCA) and enhanced its activity (Chen, J. et al. Nat Immunol 2004;5:651-7). The association is dependent on BCR activation-induced cytoplasmic tyrosine phosphorylation, because CD22 with either all six tyrosines mutated to phenylalanines or cytoplasmic tail truncated loses its ability to associate with PMCA. However, which individual or a group of tyrosine residues determine the association and how CD22 and PMCA interacts, are still unclear. In this study, by using a series of CD22 tyrosine mutants, we found that ITIM Y2/5/6 accounts for 34.3~37.1% Ca2+i inhibition but is irrelevant for CD22/PMCA association. Non-ITIM Y4 and its YEND motif contribute to the remaining 69.4~71.7% Ca2+i inhibition and is the binding site for PMCA-associated Grb2. Grb2, independently of BCR cross-linking, is constitutively associated with and directly binds to PMCA in both chicken and human B cells. Knockout of Grb2 by CRISPR/Cas9 completely disrupted the CD22/PMCA association. Thus, our results demonstrate for the first time that in addition to previously-identified ITIM/SHP-1-dependent pathway, CD22 holds a major pathway of negative regulation of Ca2+i signal, which is ITIM/SHP-1-independent, but Y4/Grb2/PMCA-dependent. PMID:27276708

Besides an ITIM/SHP-1-dependent pathway, CD22 collaborates with Grb2 and plasma membrane calcium-ATPase in an ITIM/SHP-1-independent pathway of attenuation of Ca2+i signal in B cells.

PubMed

Chen, Jie; Wang, Hong; Xu, Wei-Ping; Wei, Si-Si; Li, Hui Joyce; Mei, Yun-Qing; Li, Yi-Gang; Wang, Yue-Peng

2016-08-30

CD22 is a surface immunoglobulin implicated in negative regulation of B cell receptor (BCR) signaling; particularly inhibiting intracellular Ca2+ (Ca2+i)signals. Its cytoplasmic tail contains six tyrosine residues (Y773/Y783/Y817/Y828/Y843/Y863, designated Y1~Y6 respectively), including three (Y2/5/6) lying within immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that serve to recruit the protein tyrosine phosphatase SHP-1 after BCR activation-induced phosphorylation. The mechanism of inhibiting Ca2+i by CD22 has been poorly understood. Previous study demonstrated that CD22 associated with plasma membrane calcium-ATPase (PMCA) and enhanced its activity (Chen, J. et al. Nat Immunol 2004;5:651-7). The association is dependent on BCR activation-induced cytoplasmic tyrosine phosphorylation, because CD22 with either all six tyrosines mutated to phenylalanines or cytoplasmic tail truncated loses its ability to associate with PMCA. However, which individual or a group of tyrosine residues determine the association and how CD22 and PMCA interacts, are still unclear. In this study, by using a series of CD22 tyrosine mutants, we found that ITIM Y2/5/6 accounts for 34.3~37.1% Ca2+i inhibition but is irrelevant for CD22/PMCA association. Non-ITIM Y4 and its YEND motif contribute to the remaining 69.4~71.7% Ca2+i inhibition and is the binding site for PMCA-associated Grb2. Grb2, independently of BCR cross-linking, is constitutively associated with and directly binds to PMCA in both chicken and human B cells. Knockout of Grb2 by CRISPR/Cas9 completely disrupted the CD22/PMCA association. Thus, our results demonstrate for the first time that in addition to previously-identified ITIM/SHP-1-dependent pathway, CD22 holds a major pathway of negative regulation of Ca2+i signal, which is ITIM/SHP-1-independent, but Y4/Grb2/PMCA-dependent.

The Achromatic Light Curve of the Optical Afterglow of GRB 030226 at a Redshift of z Approximately 2

NASA Technical Reports Server (NTRS)

Klose, S.; Greiner, J.; Rau, A.; Henden, A. A.; Hartmann, D. H.; Zeh, A.; Masetti, N.; Guenther, E.; Stecklum, B.; Lindsay, K.

2003-01-01

Abstract. We report on optical and near-infrared (NIR) follow-up observations of the afterglow of GRB 030226, mainly performed with the telescopes at ESO La Silla and Paranal, with additional data obtained at other places. Our first observations started 0.2 days after the burst when the afterglow was at a magnitude of R approximately equal to 19 . One week later the magnitude of the afterglow had fallen to R=25, and at two weeks after the burst it could no longer be detected (R > 26). Our VLT blueband spectra show two absorption line systems at redshifts z = 1.962 +/- 0.001 and at z = 1.986 +/- 0.001, placing the redshift of the burster close to 2. Within our measurement errors no evidence for variations in the line strengths has been found between 0.2 and 1.2 days after the burst. An overabundance of alpha-group elements might indicate that the burst occurred in a chemically young interstellar region shaped by the nucleosynthesis from type II supernovae. The spectral slope of the afterglow shows no signs for cosmic dust along the line of sight in the GRB host galaxy, which itself remained undetected (R > 26.2). At the given redshift no supernova component affected the light from the GRB afterglow, so that the optical transient was essentially only powered by the radiation from the GRB fireball, allowing for a detailed investigation of the color evolution of the afterglow light. In our data set no obvious evidence for color changes has been found before, during, or after the smooth break in the light curve approximately 1 day after the burst. In comparison with investigations by others, our data favor the interpretation that the afterglow began to develop into a homogeneous interstellar medium before the break in the light curve became apparent.

Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis.

PubMed

Clark, Jo-Anna B J; Tully, Sara J; Dawn Marshall, H

2014-12-01

Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that presents with progressive gingival proliferation in farmed silver foxes. Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that is genetically heterogeneous with several known autosomal dominant loci. For one locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene. For the remaining loci, the molecular mechanisms are unknown but Ras pathway involvement is suspected. Here we compare sequences for the SOS1 gene, and two adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and epidermal growth factor receptor (EGFR), between HHG-affected and unaffected foxes. We conclude that the known HGF causative mutation does not cause HHG in foxes, nor do the coding regions or intron-exon boundaries of these three genes contain any candidate mutations for fox gum disease. Patterns of molecular evolution among foxes and other mammals reflect high conservation and strong functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of variability in EGFR consistent with mutational rate differences, relaxed functional constraints, and possibly positive selection.

Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors.

PubMed

Hibi, M; Hirano, T

2000-04-01

Gab1 and Gab2 (Grb2 associated binder 1 and 2) are scaffolding adapter molecules that display sequence similarity with Drosophila DOS (daughter of sevenless), which is a potential substrate for the protein tyrosine phosphatase, Corkscrew, Both Gab1 and Gab2, like DOS, have a pleckstrin homology domain and potential binding sites for SH2 and SH3 domains. Gab1 and Gab2 are phosphorylated on tyrosine upon the stimulation of various cytokines, growth factors, and antigen receptors, and interact with signaling molecules, such as Grb2, SHP-2, and PI-3 kinase. Overexpression of Gab1 or Gab2 mimics or enhances growth factor or cytokine-mediated biological processes and activates ERK MAP kinase. These data imply that Gab1 and Gab2 act downstream of a broad range of cytokine and growth factor receptors, as well as T and B antigen receptors, and link these receptors to ERK MAP kinase and biological actions.

Comparative genomic analysis of the Haloferax volcanii DS2 and Halobacterium salinarium GRB contig maps reveals extensive rearrangement.

PubMed Central

St Jean, A; Charlebois, R L

1996-01-01

Anonymous probes from the genome of Halobacterium salinarium GRB and 12 gene probes were hybridized to the cosmid clones representing the chromosome and plasmids of Halobacterium salinarium GRB and Haloferax volcanii DS2. The order of and pairwise distances between 35 loci uniquely cross-hybridizing to both chromosomes were analyzed in a search for conservation. No conservation between the genomes could be detected at the 15-kbp resolution used in this study. We found distinct sets of low-copy-number repeated sequences in the chromosome and plasmids of Halobacterium salinarium GRB, indicating some degree of partitioning between these replicons. We propose alternative courses for the evolution of the haloarchaeal genome: (i) that the majority of genomic differences that exist between genera came about at the inception of this group or (ii) that the differences have accumulated over the lifetime of the lineage. The strengths and limitations of investigating these models through comparative genomic studies are discussed. PMID:8682791

Protein Adaptations in Archaeal Extremophiles

PubMed Central

Reed, Christopher J.; Lewis, Hunter; Trejo, Eric; Winston, Vern; Evilia, Caryn

2013-01-01

Extremophiles, especially those in Archaea, have a myriad of adaptations that keep their cellular proteins stable and active under the extreme conditions in which they live. Rather than having one basic set of adaptations that works for all environments, Archaea have evolved separate protein features that are customized for each environment. We categorized the Archaea into three general groups to describe what is known about their protein adaptations: thermophilic, psychrophilic, and halophilic. Thermophilic proteins tend to have a prominent hydrophobic core and increased electrostatic interactions to maintain activity at high temperatures. Psychrophilic proteins have a reduced hydrophobic core and a less charged protein surface to maintain flexibility and activity under cold temperatures. Halophilic proteins are characterized by increased negative surface charge due to increased acidic amino acid content and peptide insertions, which compensates for the extreme ionic conditions. While acidophiles, alkaliphiles, and piezophiles are their own class of Archaea, their protein adaptations toward pH and pressure are less discernible. By understanding the protein adaptations used by archaeal extremophiles, we hope to be able to engineer and utilize proteins for industrial, environmental, and biotechnological applications where function in extreme conditions is required for activity. PMID:24151449

The Swift GRB Host Galaxy Legacy Survey

NASA Astrophysics Data System (ADS)

Perley, Daniel A.

2015-01-01

I introduce the Swift Host Galaxy Legacy Survey (SHOALS), a comprehensive multiwavelength program to characterize the demographics of the GRB host population across its entire redshift range. Using unbiased selection criteria we have designated a subset of 130 Swift gamma-ray bursts which are now being targeted with intensive observational follow-up. Deep Spitzer imaging of every field has already been obtained and analyzed, with major programs ongoing at Keck, GTC, and Gemini to obtain complementary optical/NIR photometry to enable full SED modeling and derivation of fundamental physical parameters such as mass, extinction, and star-formation rate. Using these data I will present an unbiased measurement of the GRB host-galaxy luminosity and mass functions and their evolution with redshift between z=0 and z=5, compare GRB hosts to other star-forming galaxy populations, and discuss implications for the nature of the GRB progenitor and the ability of GRBs to probe cosmic star-formation.

VizieR Online Data Catalog: GRB prompt emission fitted with the DREAM model (Ahlgren+, 2015)

NASA Astrophysics Data System (ADS)

Ahlgren, B.; Larsson, J.; Nymark, T.; Ryde, F.; Pe'Er, A.

2018-01-01

We illustrate the application of the DREAM model by fitting it to two different, bright Fermi GRBs; GRB 090618 and GRB 100724B. While GRB 090618 is well fitted by a Band function, GRB 100724B was the first example of a burst with a significant additional BB component (Guiriec et al. 2011ApJ...727L..33G). GRB 090618 is analysed using Gamma-ray Burst Monitor (GBM) data (Meegan et al. 2009ApJ...702..791M) from the NaI and BGO detectors. For GRB 100724B, we used GBM data from the NaI and BGO detectors as well as Large Area Telescope Low Energy (LAT-LLE) data. For both bursts we selected NaI detectors seeing the GRB at an off-axis angle lower than 60° and the BGO detector as being the best aligned of the two BGO detectors. The spectra were fitted in the energy ranges 8-1000 keV (NaI), 200-40000 keV (BGO) and 30-1000 MeV (LAT-LLE). (2 data files).

Classifying GRB 170817A/GW170817 in a Fermi duration-hardness plane

NASA Astrophysics Data System (ADS)

Horváth, I.; Tóth, B. G.; Hakkila, J.; Tóth, L. V.; Balázs, L. G.; Rácz, I. I.; Pintér, S.; Bagoly, Z.

2018-03-01

GRB 170817A, associated with the LIGO-Virgo GW170817 neutron-star merger event, lacks the short duration and hard spectrum of a Short gamma-ray burst (GRB) expected from long-standing classification models. Correctly identifying the class to which this burst belongs requires comparison with other GRBs detected by the Fermi GBM. The aim of our analysis is to classify Fermi GRBs and to test whether or not GRB 170817A belongs—as suggested—to the Short GRB class. The Fermi GBM catalog provides a large database with many measured variables that can be used to explore gamma-ray burst classification. We use statistical techniques to look for clustering in a sample of 1298 gamma-ray bursts described by duration and spectral hardness. Classification of the detected bursts shows that GRB 170817A most likely belongs to the Intermediate, rather than the Short GRB class. We discuss this result in light of theoretical neutron-star merger models and existing GRB classification schemes. It appears that GRB classification schemes may not yet be linked to appropriate theoretical models, and that theoretical models may not yet adequately account for known GRB class properties. We conclude that GRB 170817A may not fit into a simple phenomenological classification scheme.

Calibration of GRB Luminosity Relations with Cosmography

NASA Astrophysics Data System (ADS)

Gao, He; Liang, Nan; Zhu, Zong-Hong

For the use of gamma-ray bursts (GRBs) to probe cosmology in a cosmology-independent way, a new method has been proposed to obtain luminosity distances of GRBs by interpolating directly from the Hubble diagram of SNe Ia, and then calibrating GRB relations at high redshift. In this paper, following the basic assumption in the interpolation method that objects at the same redshift should have the same luminosity distance, we propose another approach to calibrate GRB luminosity relations with cosmographic fitting directly from SN Ia data. In cosmography, there is a well-known fitting formula which can reflect the Hubble relation between luminosity distance and redshift with cosmographic parameters which can be fitted from observation data. Using the Cosmographic fitting results from the Union set of SNe Ia, we calibrate five GRB relations using GRB sample at z ≤ 1.4 and deduce distance moduli of GRBs at 1.4 < z ≤ 6.6 by generalizing above calibrated relations at high redshift. Finally, we constrain the dark energy parameterization models of the Chevallier-Polarski-Linder (CPL) model, the Jassal-Bagla-Padmanabhan (JBP) model and the Alam model with GRB data at high redshift, as well as with the cosmic microwave background radiation (CMB) and the baryonic acoustic oscillation (BAO) observations, and we find the ΛCDM model is consistent with the current data in 1-σ confidence region.

The Discovery of an Evolving Dust Scattered X-ray Halo Around GRB 031203

NASA Technical Reports Server (NTRS)

Vaughan, S.; Willingale, R.; OBrien, P. T.; Osborne, J. P.; Reeves, J. N.; Levan, A. J.; Watson, M. G.; Tedds, J. A.; Watson, D.; Santos-Lleo, M.

2003-01-01

We report the first detection of a time-dependent, dust-scattered X-ray halo around a gamma-ray burst. GRB3 031203 was observed by XMM-Newton starting six hours after the burst. The halo appeared as concentric ring-like structures centered on the GRB location. The radii of these structures increased with time as t(sup 1/2), consistent with small-angle X-ray scattering caused by a large column of dust along the line of sight to a cosmologically distant GRB. The rings are due to dust concentrated in two distinct slabs in the Galaxy located at distances of 880 and 1390 pc, consistent with known Galactic features. The halo brightness implies an initial soft X-ray pulse consistent with the observed GRB.

LFlGRB: Luminosity function of long gamma-ray bursts

NASA Astrophysics Data System (ADS)

Paul, Debdutta

2018-04-01

LFlGRB models the luminosity function (LF) of long Gamma Ray Bursts (lGRBs) by using a sample of Swift and Fermi lGRBs to re-derive the parameters of the Yonetoku correlation and self-consistently estimate pseudo-redshifts of all the bursts with unknown redshifts. The GRB formation rate is modeled as the product of the cosmic star formation rate and a GRB formation efficiency for a given stellar mass.

The MUSE view of the host galaxy of GRB 100316D

NASA Astrophysics Data System (ADS)

Izzo, L.; Thöne, C. C.; Schulze, S.; Mehner, A.; Flores, H.; Cano, Z.; de Ugarte Postigo, A.; Kann, D. A.; Amorín, R.; Anderson, J. P.; Bauer, F. E.; Bensch, K.; Christensen, L.; Covino, S.; Della Valle, M.; Fynbo, J. P. U.; Jakobsson, P.; Klose, S.; Kuncarayakti, H.; Leloudas, G.; Milvang-Jensen, B.; Møller, P.; Puech, M.; Rossi, A.; Sánchez-Ramírez, R.; Vergani, S. D.

2017-12-01

The low distance, z = 0.0591, of GRB 100316D and its association with SN 2010bh represent two important motivations for studying this host galaxy and the GRB's immediate environment with the integral field spectrographs like Very Large Telescope/Multi-Unit Spectroscopic Explorer. Its large field of view allows us to create 2D maps of gas metallicity, ionization level and the star formation rate (SFR) distribution maps, as well as to investigate the presence of possible host companions. The host is a late-type dwarf irregular galaxy with multiple star-forming regions and an extended central region with signatures of on-going shock interactions. The gamma-ray burst (GRB) site is characterized by the lowest metallicity, the highest SFR and the youngest (∼20-30 Myr) stellar population in the galaxy, which suggest a GRB progenitor stellar population with masses up to 20-40 M⊙. We note that the GRB site has an offset of ∼660 pc from the most luminous SF region in the host. The observed SF activity in this galaxy may have been triggered by a relatively recent gravitational encounter between the host and a small undetected (LH α ≤ 1036 erg s-1) companion.

The Swift GRB Host Galaxy Legacy Survey

NASA Astrophysics Data System (ADS)

Perley, Daniel

2015-08-01

I will describe the Swift Host Galaxy Legacy Survey (SHOALS), a comprehensive multiwavelength program to characterize the demographics of the GRB host population and its redshift evolution from z=0 to z=7. Using unbiased selection criteria we have designated a subset of 119 Swift gamma-ray bursts which are now being targeted with intensive observational follow-up. Deep Spitzer imaging of every field has already been obtained and analyzed, with major programs ongoing at Keck, GTC, Gemini, VLT, and Magellan to obtain complementary optical/NIR photometry and spectroscopy to enable full SED modeling and derivation of fundamental physical parameters such as mass, extinction, and star-formation rate. Using these data I will present an unbiased measurement of the GRB host-galaxy luminosity and mass distributions and their evolution with redshift, compare GRB hosts to other star-forming galaxy populations, and discuss implications for the nature of the GRB progenitor and the ability of GRBs to serve as tools for measuring and studying cosmic star-formation in the distant universe.

A novel explosive process is required for the gamma-ray burst GRB 060614.

PubMed

Gal-Yam, A; Fox, D B; Price, P A; Ofek, E O; Davis, M R; Leonard, D C; Soderberg, A M; Schmidt, B P; Lewis, K M; Peterson, B A; Kulkarni, S R; Berger, E; Cenko, S B; Sari, R; Sharon, K; Frail, D; Moon, D-S; Brown, P J; Cucchiara, A; Harrison, F; Piran, T; Persson, S E; McCarthy, P J; Penprase, B E; Chevalier, R A; MacFadyen, A I

2006-12-21

Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

The Remarkable Afterglow of GRB 061007: Implications for Optical Flashes and GRB Fireballs

NASA Astrophysics Data System (ADS)

Mundell, C. G.; Melandri, A.; Guidorzi, C.; Kobayashi, S.; Steele, I. A.; Malesani, D.; Amati, L.; D'Avanzo, P.; Bersier, D. F.; Gomboc, A.; Rol, E.; Bode, M. F.; Carter, D.; Mottram, C. J.; Monfardini, A.; Smith, R. J.; Malhotra, S.; Wang, J.; Bannister, N.; O'Brien, P. T.; Tanvir, N. R.

2007-05-01

We present a multiwavelength analysis of Swift GRB 061007. The 2 m robotic Faulkes Telescope South began observing 137 s after the onset of the γ-ray emission, when the optical counterpart was already decaying from R~10.3 mag, and continued observing for the next 5.5 hr. These observations begin during the final γ-ray flare and continue through and beyond a long, soft tail of γ-ray emission whose flux shows an underlying simple power-law decay identical to that seen at optical and X-ray wavelengths, with temporal slope α~1.7 (F~t-α). This remarkably simple decay in all of these bands is rare for Swift bursts, which often show much more complex light curves. We suggest the afterglow emission begins as early as 30-100 s and is contemporaneous with the ongoing variable prompt emission from the central engine, but originates from a physically distinct region dominated by the forward shock. The observed multiwavelength evolution of GRB 061007 is explained by an expanding fireball whose optical, X-ray, and late-time γ-ray emission is dominated by emission from a forward shock with typical synchrotron frequency, νm, that is already below the optical band as early as t=137 s and a cooling frequency, νc, above the X-ray band to at least t=105 s. In contrast, the typical frequency of the reverse shock lies in the radio band at early time. We suggest that the unexpected lack of bright optical flashes from the majority of Swift GRBs may be explained with a low νm originating from small microphysics parameters, ɛe and ɛB. Finally, the optical light curves imply a minimum jet opening angle θ=4.7deg, and no X-ray jet break before t~106 s makes GRB 061007 a secure outlier to spectral energy correlations.

Probing the Nature of Short Swift Bursts via Deep INTEGRAL Monitoring of GRB 050925

NASA Technical Reports Server (NTRS)

Sakamoto, T.; Barbier, L.; Barthelmy, S. D.; Cummings, J. R.; Fenimore, E. E.; Gehrels, N.; Krimm, H. A.; Markwardt, C. B.; Palmer, D. M.; Parsons, A. M.;

Constraints on an Optical Afterglow and on Supernova Light Following the Short Burst GRB 050813

NASA Technical Reports Server (NTRS)

Ferrero, P.; Sanchez, S. F.; Kann, D. A.; Klose, S.; Greiner, J.; Gorosabel, J.; Hartmann, D. H.; Henden, A. A.; Moller, P.; Palazzi, E.;

An infrared flash contemporaneous with the gamma-rays of GRB 041219a.

PubMed

Blake, C H; Bloom, J S; Starr, D L; Falco, E E; Skrutskie, M; Fenimore, E E; Duchêne, G; Szentgyorgyi, A; Hornstein, S; Prochaska, J X; McCabe, C; Ghez, A; Konopacky, Q; Stapelfeldt, K; Hurley, K; Campbell, R; Kassis, M; Chaffee, F; Gehrels, N; Barthelmy, S; Cummings, J R; Hullinger, D; Krimm, H A; Markwardt, C B; Palmer, D; Parsons, A; McLean, K; Tueller, J

2005-05-12

The explosion that results in a cosmic gamma-ray burst (GRB) is thought to produce emission from two physical processes: the central engine gives rise to the high-energy emission of the burst through internal shocking, and the subsequent interaction of the flow with the external environment produces long-wavelength afterglows. Although observations of afterglows continue to refine our understanding of GRB progenitors and relativistic shocks, gamma-ray observations alone have not yielded a clear picture of the origin of the prompt emission nor details of the central engine. Only one concurrent visible-light transient has been found and it was associated with emission from an external shock. Here we report the discovery of infrared emission contemporaneous with a GRB, beginning 7.2 minutes after the onset of GRB 041219a (ref. 8). We acquired 21 images during the active phase of the burst, yielding early multi-colour observations. Our analysis of the initial infrared pulse suggests an origin consistent with internal shocks.

The First Unambiguous Electromagnetic Counterpart to a Gravitational-Wave Signal: GRB 170817A and GW170817

NASA Astrophysics Data System (ADS)

Goldstein, Adam

2018-01-01

On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 2 s prior to this GRB, the LIGO gravitational-wave observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this short GRB and the joint science that results from this discovery.

Broadband Study of GRB 091127: A Sub-Energetic Burst at Higher Redshift?

NASA Technical Reports Server (NTRS)

Troja, E.; Sakamoto, T.; Guidorzi, C.; Norris, J. P.; Panaitescu, A.; Kobayashi, S.; Omodei, N.; Brown, J. C.; Burrows, D. N.; Evans, P. A.;

the Large Aperture GRB Observatory

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

Bertou, Xavier

2009-04-30

The Large Aperture GRB Observatory (LAGO) aims at the detection of high energy photons from Gamma Ray Bursts (GRB) using the single particle technique (SPT) in ground based water Cherenkov detectors (WCD). To reach a reasonable sensitivity, high altitude mountain sites have been selected in Mexico (Sierra Negra, 4550 m a.s.l.), Bolivia (Chacaltaya, 5300 m a.s.l.) and Venezuela (Merida, 4765 m a.s.l.). We report on the project progresses and the first operation at high altitude, search for bursts in 6 months of preliminary data, as well as search for signal at ground level when satellites report a burst.

Grb-2–associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A–endothelial NOS pathway

PubMed Central

Xiong, Yan; Huo, Yingqing; Han, Jingyan; Yang, Xiao; Zhang, Rongli; Zhu, De-Sheng; Klein-Heßling, Stefan; Zhang, Xiaoyu; Han, Xiaofan; Li, Yanli; Shen, Bin; He, Yulong; Shibuya, Masabumi; Feng, Gen-Sheng; Luo, Jincai

2011-01-01

The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood. Herein we show that Grb-2–associated binder 1 (Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis. Endothelium-specific Gab1 KO (EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression. Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice. The vessels and endothelial cells (ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF. Biochemical analyses revealed a substantial reduction of endothelial NOS (eNOS) activation in Gab1-deficient vessels and ECs following VEGF stimulation. Interestingly, the phosphorylation of Akt, an enzyme known to promote VEGF-induced eNOS activation, was increased in Gab1-deficient vessels and ECs whereas protein kinase A (PKA) activity was significantly decreased. Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs. Reexpression of WT or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS. Taken together, these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation, which is dependent on PKA. Of note, this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation, suggesting considerable potential in treatment of human ischemic diseases. PMID:21282639

GRB 060605: multi-wavelength analysis of the first GRB observed using integral field spectroscopy

NASA Astrophysics Data System (ADS)

Ferrero, P.; Klose, S.; Kann, D. A.; Savaglio, S.; Schulze, S.; Palazzi, E.; Maiorano, E.; Böhm, P.; Grupe, D.; Oates, S. R.; Sánchez, S. F.; Amati, L.; Greiner, J.; Hjorth, J.; Malesani, D.; Barthelmy, S. D.; Gorosabel, J.; Masetti, N.; Roth, M. M.

2009-04-01

The long and relatively faint gamma-ray burst GRB 060605 detected by Swift/BAT lasted about 20 s. Its afterglow could be observed with Swift/XRT for nearly 1 day, while Swift/UVOT could detect the afterglow during the first 6 h after the event. Here, we report on integral field spectroscopy of its afterglow performed with PMAS/PPak mounted at the Calar Alto 3.5 m telescope. In addition, we report on a detailed analysis of XRT and UVOT data and on the results of deep late-time VLT observations that reveal the GRB host galaxy. We find that the burst occurred at a redshift of z = 3.773, possibly associated with a faint, RC = 26.4 ± 0.3 host. Based on the optical and X-ray data, we deduce information on the SED of the afterglow, the position of the cooling frequency in the SED, the nature of the circumburst environment, its collimation factor, and its energetics. We find that the GRB fireball was expanding into a constant-density medium and that the explosion was collimated with a narrow half-opening angle of about 2.4 degrees. The initial Lorentz factor of the fireball was about 250; however, its beaming-corrected energy release in the gamma-ray band was comparably low. The optical, X-ray afterglow, on the other hand, was rather luminous. Finally, we find that the data are consistent within the error bars with an achromatic evolution of the afterglow during the suspected jet break time at about 0.27 days after the burst. Based on observations collected at the German-Spanish Calar Alto Observatory in Spain (Programme F06-3.5-055) and at the European Southern Observatory, La Silla and Paranal, Chile (ESO Programme 177.D-0591).

ON THE HOST GALAXY OF GRB 150101B AND THE ASSOCIATED ACTIVE GALACTIC NUCLEUS

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

Xie, Chen; Fang, Taotao; Wang, Junfeng

We present a multi-wavelength analysis of the host galaxy of short-duration gamma-ray burst (GRB) 150101B. Follow-up optical and X-ray observations suggested that the host galaxy, 2MASX J12320498-1056010, likely harbors low-luminosity active galactic nuclei (AGNs). Our modeling of the spectral energy distribution has confirmed the nature of the AGN, making it the first reported GRB host that contains an AGN. We have also found the host galaxy is a massive elliptical galaxy with stellar population of ∼5.7 Gyr, one of the oldest among the short-duration GRB hosts. Our analysis suggests that the host galaxy can be classified as an X-ray bright,more » optically normal galaxy, and the central AGN is likely dominated by a radiatively inefficient accretion flow. Our work explores an interesting connection that may exist between GRB and AGN activities of the host galaxy, which can help in understanding the host environment of the GRB events and the roles of AGN feedback.« less

Fermi-LAT observations of the gamma-ray burst GRB 130427A.

PubMed

Ackermann, M; Ajello, M; Asano, K; Atwood, W B; Axelsson, M; Baldini, L; Ballet, J; Barbiellini, G; Baring, M G; Bastieri, D; Bechtol, K; Bellazzini, R; Bissaldi, E; Bonamente, E; Bregeon, J; Brigida, M; Bruel, P; Buehler, R; Burgess, J Michael; Buson, S; Caliandro, G A; Cameron, R A; Caraveo, P A; Cecchi, C; Chaplin, V; Charles, E; Chekhtman, A; Cheung, C C; Chiang, J; Chiaro, G; Ciprini, S; Claus, R; Cleveland, W; Cohen-Tanugi, J; Collazzi, A; Cominsky, L R; Connaughton, V; Conrad, J; Cutini, S; D'Ammando, F; de Angelis, A; DeKlotz, M; de Palma, F; Dermer, C D; Desiante, R; Diekmann, A; Di Venere, L; Drell, P S; Drlica-Wagner, A; Favuzzi, C; Fegan, S J; Ferrara, E C; Finke, J; Fitzpatrick, G; Focke, W B; Franckowiak, A; Fukazawa, Y; Funk, S; Fusco, P; Gargano, F; Gehrels, N; Germani, S; Gibby, M; Giglietto, N; Giles, M; Giordano, F; Giroletti, M; Godfrey, G; Granot, J; Grenier, I A; Grove, J E; Gruber, D; Guiriec, S; Hadasch, D; Hanabata, Y; Harding, A K; Hayashida, M; Hays, E; Horan, D; Hughes, R E; Inoue, Y; Jogler, T; Jóhannesson, G; Johnson, W N; Kawano, T; Knödlseder, J; Kocevski, D; Kuss, M; Lande, J; Larsson, S; Latronico, L; Longo, F; Loparco, F; Lovellette, M N; Lubrano, P; Mayer, M; Mazziotta, M N; McEnery, J E; Michelson, P F; Mizuno, T; Moiseev, A A; Monzani, M E; Moretti, E; Morselli, A; Moskalenko, I V; Murgia, S; Nemmen, R; Nuss, E; Ohno, M; Ohsugi, T; Okumura, A; Omodei, N; Orienti, M; Paneque, D; Pelassa, V; Perkins, J S; Pesce-Rollins, M; Petrosian, V; Piron, F; Pivato, G; Porter, T A; Racusin, J L; Rainò, S; Rando, R; Razzano, M; Razzaque, S; Reimer, A; Reimer, O; Ritz, S; Roth, M; Ryde, F; Sartori, A; Parkinson, P M Saz; Scargle, J D; Schulz, A; Sgrò, C; Siskind, E J; Sonbas, E; Spandre, G; Spinelli, P; Tajima, H; Takahashi, H; Thayer, J G; Thayer, J B; Thompson, D J; Tibaldo, L; Tinivella, M; Torres, D F; Tosti, G; Troja, E; Usher, T L; Vandenbroucke, J; Vasileiou, V; Vianello, G; Vitale, V; Winer, B L; Wood, K S; Yamazaki, R; Younes, G; Yu, H-F; Zhu, S J; Bhat, P N; Briggs, M S; Byrne, D; Foley, S; Goldstein, A; Jenke, P; Kippen, R M; Kouveliotou, C; McBreen, S; Meegan, C; Paciesas, W S; Preece, R; Rau, A; Tierney, D; van der Horst, A J; von Kienlin, A; Wilson-Hodge, C; Xiong, S; Cusumano, G; La Parola, V; Cummings, J R

2014-01-03

The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest γ-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.

Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Asano, K.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Baring, M. G.; Bastieri, D.;

A Different Point of View towards GRB 031203

NASA Technical Reports Server (NTRS)

Ramirez-Ruiz, E.; Granot, J.; Kouveliotou, C.; Woosley, S. E.; Patel, S. K.; Mazzali, P. A.

2004-01-01

One of the most fundamental characteristics of any explosion is its energy, yet despite lively debates, the gamma-ray burst (GRB) community has still to reach a consensus on whether GRBs are standard bombs with a total energy in their relativistic ejecta approximately 10(exp 51) ergs, or a broad range of phenomena with energies varying by many orders of magnitude. While low energy GRBs may well exist, we show here that observations of GRB 031203, do not require a sub-energetic nature for that event. In fact, contrary to previous claims, the data are more consistent with a typical, powerful GRB seen at an angle of about twice the opening angle of the central jet.

Determining the Lorentz Factor and Viewing Angle of GRB 170817A

NASA Astrophysics Data System (ADS)

Zou, Yuan-Chuan; Wang, Fei-Fei; Moharana, Reetanjali; Liao, Bin; Chen, Wei; Wu, Qingwen; Lei, Wei-Hua; Wang, Fa-Yin

2018-01-01

The weak short gamma-ray burst (GRB) 170817A was accompanied by the GW170817 gravitational-wave event and is believed to have been produced by an off-beam relativistic jet. Here, we use the {E}{{p},{{i}}}{--}{E}{iso} and {{Γ }}{--}{E}{iso} relations to determine its Lorentz factor Γ and the viewing angle from the edge of the jet {θ }{obs}{\\prime } of GRB 170817A. Our results indicate that {{Γ }}={13.4}-5.5+9.8 and {θ }{obs}{\\prime }=4\\buildrel{\\circ}\\over{.} {3}-1.5+1.8, corresponding to an on-axis {E}{{p},{{i}}}={415}-167+361 {keV} and {E}{iso}=({2.4}-1.9+1.6)× {10}47 erg. Therefore, the GRB was an intrinsically weak short GRB. We also find that the afterglow emission was in good agreement with the follow-up multiband observations and that the radio emissions at around 20 days may have come from the off-axis jet. Interestingly, the Doppler factor and luminosity follow a universal relation for GRBs and blazars, thus suggesting that they may share a similar radiation mechanism.

Gab2 Phosphorylation by RSK Inhibits Shp2 Recruitment and Cell Motility

PubMed Central

Zhang, Xiaocui; Lavoie, Genevieve; Fort, Loic; Huttlin, Edward L.; Tcherkezian, Joseph; Galan, Jacob A.; Gu, Haihua; Gygi, Steven P.; Carreno, Sebastien

2013-01-01

The scaffolding adapter protein Gab2 (Grb2-associated binder) participates in the signaling response evoked by various growth factors and cytokines. Gab2 is overexpressed in several human malignancies, including breast cancer, and was shown to promote mammary epithelial cell migration. The role of Gab2 in the activation of different signaling pathways is well documented, but less is known regarding the feedback mechanisms responsible for its inactivation. We now demonstrate that activation of the Ras/mitogen-activated protein kinase (MAPK) pathway promotes Gab2 phosphorylation on basic consensus motifs. More specifically, we show that RSK (p90 ribosomal S6 kinase) phosphorylates Gab2 on three conserved residues, both in vivo and in vitro. Mutation of these phosphorylation sites does not alter Gab2 binding to Grb2, but instead, we show that Gab2 phosphorylation inhibits the recruitment of the tyrosine phosphatase Shp2 in response to growth factors. Expression of an unphosphorylatable Gab2 mutant in mammary epithelial cells promotes an invasion-like phenotype and increases cell motility. Taken together, these results suggest that RSK is part of a negative-feedback loop that restricts Gab2-dependent epithelial cell motility. On the basis of the widespread role of Gab2 in receptor signaling, these findings also suggest that RSK plays a regulatory function in diverse receptor systems. PMID:23401857

Chandra Observations of the X-Ray Environs of SN 1998BW / GRB 980425

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

Kouveliotou , C.

2004-07-14

We report X-ray studies of the environs of SN 1998bw and GRB 980425 using the Chandra X-Ray Observatory 1281 days after the GRB. Eight X-ray point sources were localized, three and .ve each in the original error boxes--S1 and S2--assigned for variable X-ray counterparts to the GRB by BeppoSAX. The sum of the discrete X-ray sources plus continuous emission in S2 observed by CXO on day 1281 is within a factor of 1.5 of the maximum and the upper limits seen by BeppoSAX. We conclude that S2 is the sum of several variable sources that have not disappeared, and thereforemore » is not associated with the GRB. Within S1, clear evidence is seen for a decline of approximately a factor of 12 between day 200 and day 1281. One of the sources in S1, S1a, is coincident with the well-determined radio location of SN 1998bw, and is certainly the remnant of that explosion. The nature of the other sources is also discussed. Combining our observation of the supernova with others of the GRB afterglow, a smooth X-ray light curve, spanning {approx} 1300 days, is obtained by assuming the burst and supernova were coincident at 35.6 Mpc. When this X-ray light curve is compared with those of the X-ray ''afterglows'' of ordinary GRBs, X-ray Flashes, and ordinary supernovae, evidence emerges for at least two classes of lightcurves, perhaps bounding a continuum. By three to ten years, all these phenomena seem to converge on a common X-ray luminosity, possibly indicative of the supernova underlying them all. This convergence strengthens the conclusion that SN 1998bw and GRB 980425 took place in the same object. One possible explanation for the two classes is a (nearly) standard GRB observed at different angles, in which case X-ray afterglows with intermediate luminosities should eventually be discovered. Finally, we comment on the contribution of GRBs to the ULX source population.« less

A Spatially Resolved Study of the GRB 020903 Host Galaxy

NASA Astrophysics Data System (ADS)

Thorp, Mallory D.; Levesque, Emily M.

2018-03-01

GRB 020903 is a long-duration gamma-ray burst with a host galaxy close enough and extended enough for spatially resolved observations, making it one of less than a dozen GRBs where such host studies are possible. GRB 020903 lies in a galaxy host complex that appears to consist of four interacting components. Here we present the results of spatially resolved spectroscopic observations of the GRB 020903 host. By taking observations at two different position angles, we were able to obtain optical spectra (3600–9000 Å) of multiple regions in the galaxy. We confirm redshifts for three regions of the host galaxy that match that of GRB 020903. We measure the metallicity of these regions, and find that the explosion site and the nearby star-forming regions both have comparable subsolar metallicities. We conclude that, in agreement with past spatially resolved studies of GRBs, the GRB explosion site is representative of the host galaxy as a whole rather than localized in a metal-poor region of the galaxy.

The SEDs and Host Galaxies of the Dustiest GRB Afterglows

NASA Technical Reports Server (NTRS)

Kruhler, T.; Greiner, J.; Schady, P.; Savaglio, S.; Afonso, P. M. J.; Clemens, C.; Elliott, J.; Filgas, R.; Gruber, D.; Kann, D. A.;

CONSTRAINTS ON VERY HIGH ENERGY EMISSION FROM GRB 130427A

DOE PAGES

Aliu, E.; Aune, T.; Barnacka, A.; ...

2014-10-10

In this study, prompt emission from the very fluent and nearby (z = 0.34) gamma-ray burst GRB 130427A was detected by several orbiting telescopes and by ground-based, wide-field-of-view optical transient monitors. Apart from the intensity and proximity of this GRB, it is exceptional due to the extremely long-lived high-energy (100 MeV to 100 GeV) gamma-ray emission, which was detected by the Large Area Telescope on the Fermi Gamma-Ray Space Telescope for ~70 ks after the initial burst. The persistent, hard-spectrum, high-energy emission suggests that the highest-energy gamma rays may have been produced via synchrotron self-Compton processes though there is alsomore » evidence that the high-energy emission may instead be an extension of the synchrotron spectrum. VERITAS, a ground-based imaging atmospheric Cherenkov telescope array, began follow-up observations of GRB 130427A ~71 ks (~20 hr) after the onset of the burst. The GRB was not detected with VERITAS; however, the high elevation of the observations, coupled with the low redshift of the GRB, make VERITAS a very sensitive probe of the emission from GRB 130427A for E > 100 GeV. In conclusion, the non-detection and consequent upper limit derived place constraints on the synchrotron self-Compton model of high-energy gamma-ray emission from this burst.« less

Broadband Study of GRB 091127: A Sub-energetic Burst at Higher Redshift?

NASA Astrophysics Data System (ADS)

Troja, E.; Sakamoto, T.; Guidorzi, C.; Norris, J. P.; Panaitescu, A.; Kobayashi, S.; Omodei, N.; Brown, J. C.; Burrows, D. N.; Evans, P. A.; Gehrels, N.; Marshall, F. E.; Mawson, N.; Melandri, A.; Mundell, C. G.; Oates, S. R.; Pal'shin, V.; Preece, R. D.; Racusin, J. L.; Steele, I. A.; Tanvir, N. R.; Vasileiou, V.; Wilson-Hodge, C.; Yamaoka, K.

2012-12-01

GRB 091127 is a bright gamma-ray burst (GRB) detected by Swift at a redshift z = 0.49 and associated with SN 2009nz. We present the broadband analysis of the GRB prompt and afterglow emission and study its high-energy properties in the context of the GRB/SN association. While the high luminosity of the prompt emission and standard afterglow behavior are typical of cosmological long GRBs, its low-energy release (E γ < 3 × 1049 erg), soft spectrum, and unusual spectral lag connect this GRB to the class of sub-energetic bursts. We discuss the suppression of high-energy emission in this burst, and investigate whether this behavior could be connected with the sub-energetic nature of the explosion.

Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A

DOE PAGES

Ackermann, M.; Ajello, M.; Asano, K.; ...

2013-11-21

The Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources using the observations of the exceptionally bright gamma-ray burst (GRB) 130427A. We found that GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest γ-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.

OT1_mhuang01_1: GRB Afterglow Photometry with Herschel Infrared Cameras

NASA Astrophysics Data System (ADS)

Huang, M.

2010-07-01

GRB Afterglow Photometry with Herschel Infrared Cameras (GRAPHICS) Gamma-ray bursts (GRBs) are the most luminous explosions in the universe. It has been difficult to obtain a full spectral picture of the phenomena in the short period when GRBs become ``alive'', i.e. when they generate bursts in Gamma-ray and produce afterglows in other wavelengths. Between NIR (12micron) and submillimeter (850micron) there lies nearly two orders of magnitude of spectral range where GRB afterglows have never been detected. Herschel is unique in its cutting edge sensitivity, efficiency, and readiness in FIR observations, and is capable of detecting GRB afterglows. Observing GRB afterglows with Herschel would greatly enrich our understanding of GRB physics and conditions of the Universe in early epochs. We propose Target of Opportunity studies using the SPIRE and PACS instruments of Herschel to observe 3 bright GRB afterglows, each within a few hours to a few tens of days after burst. We will make follow-up observations after the initial one to photometrically measure GRB light curves and IR SEDs. We will make ground optical observations to compliment Herschel data, and have the the GRB community informed. Observing the forward shock peak in the FIR light curve and compare it (both the flux and time) with those in the optical and radio bands would give a unambiguous test to the fireball model, and offer a direct measurement of the density profile of the circumburst material. Catching the short-lived reverse shock emission and measure its magnitude would lead to constraints on some important parameters of the GRB ejecta and address the unknown composition of GRBs, baryonic vs. magnetic.

Short GRBs: Opening Angles, Local Neutron Star Merger Rate, and Off-axis Events for GRB/GW Association

NASA Astrophysics Data System (ADS)

Jin, Zhi-Ping; Li, Xiang; Wang, Hao; Wang, Yuan-Zhu; He, Hao-Ning; Yuan, Qiang; Zhang, Fu-Wen; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

2018-04-01

The jet breaks in the afterglow light curves of short gamma-ray bursts (SGRBs), rarely detected so far, are crucial for estimating the half-opening angles of the ejecta (θ j) and hence the neutron star merger rate. In this work, we report the detection of jet decline behaviors in GRB 150424A and GRB 160821B, and find θ j ∼ 0.1 rad. Together with five events reported before 2015 and three others “identified” recently (GRB 050709, GRB 060614, and GRB 140903A), we have a sample consisting of nine SGRBs and one long-short GRB with reasonably estimated θ j. In particular, three Swift bursts in the sample have redshifts z ≤ 0.2, with which we estimate the local neutron star merger rate density to be ∼ {1109}-657+1432 {Gpc}}-3 {yr}}-1 or {162}-83+140 {Gpc}}-3 {yr}}-1 if the narrowly beamed GRB 061201 is excluded. Inspired by the typical θ j ∼ 0.1 rad found currently, we further investigate whether the off-beam GRBs (in the uniform jet model) or the off-axis events (in the structured jet model) can significantly enhance the GRB/GW association. For the former, the enhancement is at most moderate, while for the latter the enhancement can be much greater and a high GRB/GW association probability of ∼10% is possible. We also show that the data of GRB 160821B may contain a macronova/kilonova emission component with a temperature of ∼3100 K at ∼3.6 days after the burst and more data are needed to ultimately clarify.

Firework Model: Time Dependent Spectral Evolution of GRB

NASA Astrophysics Data System (ADS)

Barbiellini, Guido; Longo, Francesco; Ghirlanda, G.; Celotti, A.; Bosnjak, Z.

2004-09-01

The energetics of the long duration GRB phenomenon is compared with models of a rotating BH in a strong magnetic field generated by an accreting torus. The GRB energy emission is attributed to magnetic field vacuum breakdown that gives origin to a e +/- fireball. Its subsequent evolution is hypothesized in analogy with the in-flight decay of an elementary particle. An anisotropy in the fireball propagation is thus naturally produced. The recent discovery in some GRB of an initial phase characterized by a thermal spectrum could be interpreted as the photon emission of the fireball photosphere when it becomes transparent. In particular, the temporal evolution of the emission can be explained as the effect of a radiative deceleration of the out-moving ejecta.

On the nature of the extremely fast optical rebrightening of the afterglow of GRB 081029

NASA Astrophysics Data System (ADS)

Nardini, M.; Greiner, J.; Krühler, T.; Filgas, R.; Klose, S.; Afonso, P.; Clemens, C.; Guelbenzu, A. N.; Olivares E., F.; Rau, A.; Rossi, A.; Updike, A.; Küpcü Yoldaş, A.; Yoldaş, A.; Burlon, D.; Elliott, J.; Kann, D. A.

2011-07-01

Context. After the launch of the Swift satellite, the gamma-ray burst (GRB) optical light-curve smoothness paradigm has been questioned thanks to the faster and better sampled optical follow-up, which has unveiled a very complex behaviour. This complexity is triggering the interest of the whole GRB community. The GROND multi-channel imager is used to study optical and near-infrared (NIR) afterglows of GRBs with unprecedented optical and near-infrared temporal and spectral resolution. The GRB 081029 has a very prominent optical rebrightening event and is an outstanding example of the application of the multi-channel imager to GRB afterglows. Aims: Here we exploit the rich GROND multi-colour follow-up of GRB 081029 combined with XRT observations to study the nature of late-time rebrightenings that appear in the optical-NIR light-curves of some GRB afterglows. Methods: We analyse the optical and NIR observations obtained with the seven-channel Gamma-Ray burst Optical and Near-infrared Detector (GROND) at the 2.2 m MPI/ESO telescope and the X-ray data obtained with the XRT telescope on board the Swift observatory. The multi-wavelength temporal and spectral evolution is discussed in the framework of different physical models. Results: The extremely steep optical and NIR rebrightening observed in GRB 081029 cannot be explained in the framework of the standard forward shock afterglow model. The absence of a contemporaneous X-ray rebrightening and the evidence of a strong spectral evolution in the optical-NIR bands during the rise suggest two separate components that dominate in the early and late-time light-curves, respectively. The steepness of the optical rise cannot be explained even in the framework of the alternative scenarios proposed in the literature unless a late-time activity of the central engine is assumed. Full GROND photometry of GRB 081029 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http

Time-resolved GRB spectra in the complex radiation of synchrotron and Compton processes

NASA Astrophysics Data System (ADS)

Jiang, Y. G.; Hu, S. M.; Chen, X.; Li, K.; Guo, D. F.; Li, Y. T.; Li, H. Z.; Zhao, Y. Y.; Lin, H. N.; Chang, Z.

2016-03-01

Under the steady-state condition, the spectrum of electrons is investigated by solving the continuity equation under the complex radiation of both the synchrotron and Compton processes. The resulted gamma-ray burst (GRB) spectrum is a broken power law in both the fast and slow cooling phases. On the basis of this electron spectrum, the spectral indices of the Band function in four different phases are presented. In the complex radiation frame, the detail investigation on physical parameters reveals that three models can answer the α ˜ -1 problem, which are the synchrotron plus synchrotron self-Compton in the internal and the external shock models, and the synchrotron plus the external Compton processes in the external shock model. A possible marginal to fast cooling phase transition in GRB 080916C is discussed. The time-resolved spectra in different main pulses of GRB 100724B, GRB 100826A and GRB 130606B are investigated. We found that the flux is proportional to the peak energy in almost all main pulses. A significant (5σ) correlation for Fp ˜ Ep is evident the first main pulse of GRB 100826A, and three marginally significant (3σ) correlations Fp ˜ Ep are found in main pulses of GRB 100826A and GRB 130606B. The correlation between spectral index and Ep at 3 ˜ 4σ level are observed in the first main pulse of GRB 100826A. Such correlations are possible explained in the complex radiation scenario.

Broadband Study of GRB 091127: A Sub-Energetic Burst at Higher Redshift?

DOE PAGES

Troja, E.; Sakamoto, T.; Guidorzi, C.; ...

2012-11-21

GRB 091127 is a bright gamma-ray burst (GRB) detected by Swift at a redshift z = 0.49 and associated with SN 2009nz. In this paper, we present the broadband analysis of the GRB prompt and afterglow emission and study its high-energy properties in the context of the GRB/SN association. While the high luminosity of the prompt emission and standard afterglow behavior are typical of cosmological long GRBs, its low-energy release (E γ < 3 x 10 49 erg), soft spectrum, and unusual spectral lag connect this GRB to the class of sub-energetic bursts. Finally, we discuss the suppression of high-energymore » emission in this burst, and investigate whether this behavior could be connected with the sub-energetic nature of the explosion.« less

FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

PubMed

Yuan, Haiming; Huang, Linhuan; Hu, Xizi; Li, Qian; Sun, Xiaofang; Xie, Yingjun; Kong, Shu; Wang, Xiaoman

2016-07-02

Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

Multicolour modelling of SN 2013dx associated with GRB 130702A★

NASA Astrophysics Data System (ADS)

Volnova, A. A.; Pruzhinskaya, M. V.; Pozanenko, A. S.; Blinnikov, S. I.; Minaev, P. Yu.; Burkhonov, O. A.; Chernenko, A. M.; Ehgamberdiev, Sh. A.; Inasaridze, R.; Jelinek, M.; Khorunzhev, G. A.; Klunko, E. V.; Krugly, Yu. N.; Mazaeva, E. D.; Rumyantsev, V. V.; Volvach, A. E.

2017-05-01

We present optical observations of SN 2013dx, related to the Fermi burst GRB 130702A, which occurred at red shift z = 0.145. It is the second-best sampled gamma-ray burst (GRB)/supernova (SN) after SN 1998bw. The observational light curves contain more than 280 data points in the uBgrRiz filters until 88 d after the burst, and the data were collected from our observational collaboration (Maidanak Observatory, Abastumani Observatory, Crimean Astrophysical Observatory, Mondy Observatory, National Observatory of Turkey and Observatorio del Roque de los Muchachos) and from the literature. We model numerically the multicolour light curves using the one-dimensional radiation hydrodynamical code stella, previously widely implemented for modelling typical non-GRB SNe. The best-fitting model has the following parameters: pre-SN star mass M = 25 M⊙; mass of the compact remnant MCR = 6 M⊙; total energy of the outburst Eoburst = 3.5 × 1052 erg; pre-supernova star radius R = 100 R⊙; M_^{56Ni} = 0.2 M_{⊙}, which is totally mixed through the ejecta; MO = 16.6 M⊙; MSi = 1.2 M⊙ and MFe = 1.2 M⊙, and the radiative efficiency of the SN is 0.1 per cent.

GRB 971214

NASA Astrophysics Data System (ADS)

Kulkarni, S. R.; Adelberger, K. L.; Bloom, J. S.; Kundic, T.; Lubin, L.

1998-01-01

On December 28, 1997, Kundic and Lubin obtained spectra of the optical transient of GRB 971214 (IAUC #6788) with the Low Resolution Imaging Spectrograph (LRIS) mounted on the Keck II telescope. The seeing conditions were excellent. If the transient continued the power-law decay as indicated by the data from Halpern et al. (IAUC #6788) then by this epoch the light at this position should be dominated by the host (cf. Kulkarni et al. GCN #27; ATEL #5).

HAPPY BIRTHDAY SWIFT: ULTRA-LONG GRB 141121A AND ITS BROADBAND AFTERGLOW

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

Cucchiara, A.; Veres, P.; Corsi, A.

2015-10-20

We present our extensive observational campaign on the Swift-discovered GRB 141121A, almost 10 years after its launch. Our observations cover radio through X-rays and extend for more than 30 days after discovery. The prompt phase of GRB 141121A lasted 1410 s and, at the derived redshift of z = 1.469, the isotropic energy is E{sub γ,iso} = 8.0 × 10{sup 52} erg. Due to the long prompt duration, GRB 141121A falls into the recently discovered class of ultra-long GRBs (UL-GRBs). Peculiar features of this burst are (1) a flat early-time optical light curve and (2) a radio-to-X-ray rebrightening around threemore » days after the burst. The latter is followed by a steep optical-to-X-ray decay and a much shallower radio fading. We analyze GRB 141121A in the context of the standard forward–reverse shock (FS, RS) scenario and we disentangle the FS and RS contributions. Finally, we comment on the puzzling early-time (t ≲ 3 days) behavior of GRB 141121A, and suggest that its interpretation may require a two-component jet model. Overall, our analysis confirms that the class of UL-GRBs represents our best opportunity to firmly establish the prominent emission mechanisms in action during powerful gamma-ray burst explosions, and future missions (like SVOM, XTiDE, or ISS-Lobster) will provide many more of such objects.« less

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes

PubMed Central

Castoe, Todd A.; de Koning, A. P. Jason; Hall, Kathryn T.; Card, Daren C.; Schield, Drew R.; Fujita, Matthew K.; Ruggiero, Robert P.; Degner, Jack F.; Daza, Juan M.; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J.; Castoe, Jill M.; Fox, Samuel E.; Poole, Alex W.; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W.; Li, Qing; Schott, Ryan K.; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A.; Hoffmann, Federico G.; Bogden, Robert; Smith, Eric N.; Chang, Belinda S. W.; Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Richardson, Michael K.; Mackessy, Stephen P.; Bronikowski, Anne M.; Yandell, Mark; Warren, Wesley C.; Secor, Stephen M.; Pollock, David D.

2013-01-01

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome. PMID:24297902

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.

PubMed

Castoe, Todd A; de Koning, A P Jason; Hall, Kathryn T; Card, Daren C; Schield, Drew R; Fujita, Matthew K; Ruggiero, Robert P; Degner, Jack F; Daza, Juan M; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J; Castoe, Jill M; Fox, Samuel E; Poole, Alex W; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W; Li, Qing; Schott, Ryan K; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A; Hoffmann, Federico G; Bogden, Robert; Smith, Eric N; Chang, Belinda S W; Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Richardson, Michael K; Mackessy, Stephen P; Bronikowski, Anne M; Bronikowsi, Anne M; Yandell, Mark; Warren, Wesley C; Secor, Stephen M; Pollock, David D

2013-12-17

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

Revealing Physical Activity of GRB Central Engine with Macronova/Kilonova Data

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

Shen, Zhao-Qiang; Jin, Zhi-Ping; Liang, Yun-Feng

The modeling of Li-Paczyński macronova/kilonova signals gives a reasonable estimate on the neutron-rich material ejected during the neutron star mergers. Usually the accretion disk is more massive than the macronova ejecta, with which the efficiencies of converting the disk mass into prompt emission of three merger-driven GRBs can hence be directly constrained. Supposing the macronovae/kilonovae associated with GRB 050709, GRB 060614, and GRB 130603B arose from radioactive decay of the r -process material, the upper limit on energy conversion efficiencies are found to be as low as ∼10{sup −6}–10{sup −4}. Moreover, for all three events, neutrino annihilation is likely powerfulmore » enough to account for the brief gamma-ray flashes. Neutrino annihilation can also explain the “extended” emission lasting ∼100 s in GRB 050709, but does not work for the one in GRB 060614. These progresses demonstrate that the macronova can serve as a novel probe of the central engine activity.« less

ALMA and RATIR observations of GRB 131030A

NASA Astrophysics Data System (ADS)

Huang, Kuiyun; Urata, Yuji; Takahashi, Satoko; Im, Myungshin; Yu, Po-Chieh; Choi, Changsu; Butler, Nathaniel; Watson, Alan M.; Kutyrev, Alexander; Lee, William H.; Klein, Chris; Fox, Ori D.; Littlejohns, Owen; Cucchiara, Nino; Troja, Eleonora; González, Jesús; Richer, Michael G.; Román-Zúñiga, Carlos; Bloom, Josh; Prochaska, J. Xavier; Gehrels, Neil; Moseley, Harvey; Georgiev, Leonid; de Diego, José A.; Ramirez-Ruiz, Enrico

2017-04-01

We report on the first open-use based Atacama Large Millimeter/submm Array (ALMA) 345 GHz observation for the late afterglow phase of GRB 131030A. The ALMA observation constrained a deep limit at 17.1 d for the afterglow and host galaxy. We also identified a faint submillimeter source (ALMA J2300-0522) near the GRB 131030A position. The deep limit at 345 GHz and multifrequency observations obtained using Swift and RATIR yielded forward-shock modeling with a two-dimensional relativistic hydrodynamic jet simulation and described X-ray excess in the afterglow. The excess was inconsistent with the synchrotron self-inverse Compton radiation from the forward shock. The host galaxy of GRB 131030A and optical counterpart of ALMA J2300-0522 were also identified in the Subaru image. Based on the deep ALMA limit for the host galaxy, the 3σ upper limits of IR luminosity and the star formation rate (SFR) are estimated as LIR < 1.11 × 1011 L⊙ and SFR <18.7 (M⊙ yr-1), respectively. Although the separation angle from the burst location (3{^''.}5) was rather large, ALMA J2300-0522 may be one component of the GRB 131030A host galaxy, according to previous host galaxy cases.

T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2

PubMed Central

Dong, Shen; Corre, Béatrice; Foulon, Eliane; Dufour, Evelyne; Veillette, André; Acuto, Oreste; Michel, Frédérique

2006-01-01

Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance. PMID:17043143

Spitzer Observations of GRB Hosts: A Legacy Approach

NASA Astrophysics Data System (ADS)

Perley, Daniel; Tanvir, Nial; Hjorth, Jens; Berger, Edo; Laskar, Tanmoy; Michalowski, Michal; Chary, Ranga-Ram; Fynbo, Johan; Levan, Andrew

2012-09-01

The host galaxies of long-duration GRBs are drawn from uniquely broad range of luminosities and redshifts. Thus they offer the possibility of studying the evolution of star-forming galaxies without the limitations of other luminosity-selected samples, which typically are increasingly biased towards the most massive systems at higher redshift. However, reaping the full benefits of this potential requires careful attention to the selection biases affecting host identification. To this end, we propose observations of a Legacy sample of 70 GRB host galaxies (an additional 70 have already been observed by Spitzer), in order to constrain the mass and luminosity function in GRB-selected galaxies at high redshift, including its dependence on redshift and on properties of the afterglow. Crucially, and unlike previous Spitzer surveys, this sample is carefully designed to be uniform and free of optical selection biases that have caused previous surveys to systematically under-represent the role of luminous, massive hosts. We also propose to extend to larger, more powerfully constraining samples the study of two science areas where Spitzer observations have recently shown spectacular success: the hosts of dust-obscured GRBs (which promise to further our understanding of the connection between GRBs and star-formation in the most luminous galaxies), and the evolution of the mass-metallicity relation at z>2 (for which GRB host observations provide particularly powerful constraints on high-z chemical evolution).

CGM-GRB: A survey of the CircumGalactic Medium around GRB hosts

NASA Astrophysics Data System (ADS)

Gatkine, Pradip; Veilleux, Sylvain; Cucchiara, Antonino; Cenko, Bradley

2018-01-01

Recent space- and ground-based studies of the circumgalactic medium around galaxies have revealed the dynamic interplay between the galaxy ecosystem and surrounding CGM using bright background quasars. Here, we extend this investigation of the CGM to higher redshifts by using the bright afterglows of gamma-ray bursts as background sources. This provides a unique opportunity to probe the host galaxy ISM and its surrounding CGM together. We compiled a sample of 25 high-resolution (R > 8000) and high-quality (typical S/N ~ 20) rest-frame UV spectra of GRB afterglows with a redshift range (1.5 < z < 5.9) obtained using Keck-HIRES, VLT-UVES, and VLT-X-shooter spectrographs. We fit multi-component Voigt profiles to several absorption lines of both high-ionization (O VI, C IV, Si IV, etc) and low-ionization species (Si II, C II, Fe II, etc) to extract the column densities (N), Doppler parameters (b) and line-centroids. The preliminary results of our analysis on the kinematics and physical properties of the ISM and CGM of these GRB hosts are presented here.

Radioactive decay of the late-time light curves of GRB-SNe

NASA Astrophysics Data System (ADS)

Misra, Kuntal; Fruchte, Andrew Steven

2018-04-01

We present the late-time Hubble Space Telescope observations of two GRB associated supernovae, GRB 030329/SN 2003dh and XRF 060218/SN 2006aj. Using the multi-color data upto ˜ 320 days after the burst, we constrain the late-time decay nature of these supernovae. The decay rates of SN 2003dh are steeper than SN 2006aj. A comparison with two other GRB supernovae, GRB 980425/SN 1998bw and the supernova associated with XRF 020903, shows that the decay rates of SN 2003dh are similar to XRF 020903 and those of SN 2006aj are similar to SN 1998bw. The late-time decay rates are steeper than the 56Co?56Fe radioactive decay rate (0.0098 mag day-1) indicating that there is some leakage of gamma-rays.

Confronting GRB prompt emission with a model for subphotospheric dissipation

DOE PAGES

Ahlgren, Björn; Larsson, Josefin; Nymark, Tanja; ...

2015-09-16

The origin of the prompt emission in gamma-ray bursts (GRBs) is still an unsolved problem and several different mechanisms have been suggested. We fit Fermi GRB data with a photospheric emission model which includes dissipation of the jet kinetic energy below the photosphere. The resulting spectra are dominated by Comptonization and contain no significant contribution from synchrotron radiation. In order to fit to the data, we span a physically motivated part of the model's parameter space and create DREAM (Dissipation with Radiative Emission as A table Model), a table model for XSPEC. Here, we show that this model can describemore » different kinds of GRB spectra, including GRB 090618, representing a typical Band function spectrum, and GRB 100724B, illustrating a double peaked spectrum, previously fitted with a Band+blackbody model, suggesting they originate from a similar scenario. We also suggest that the main difference between these two types of bursts is the optical depth at the dissipation site.« less

The optical afterglow of the short gamma-ray burst GRB 050709.

PubMed

Hjorth, Jens; Watson, Darach; Fynbo, Johan P U; Price, Paul A; Jensen, Brian L; Jørgensen, Uffe G; Kubas, Daniel; Gorosabel, Javier; Jakobsson, Páll; Sollerman, Jesper; Pedersen, Kristian; Kouveliotou, Chryssa

2005-10-06

It has long been known that there are two classes of gamma-ray bursts (GRBs), mainly distinguished by their durations. The breakthrough in our understanding of long-duration GRBs (those lasting more than approximately 2 s), which ultimately linked them with energetic type Ic supernovae, came from the discovery of their long-lived X-ray and optical 'afterglows', when precise and rapid localizations of the sources could finally be obtained. X-ray localizations have recently become available for short (duration <2 s) GRBs, which have evaded optical detection for more than 30 years. Here we report the first discovery of transient optical emission (R-band magnitude approximately 23) associated with a short burst: GRB 050709. The optical afterglow was localized with subarcsecond accuracy, and lies in the outskirts of a blue dwarf galaxy. The optical and X-ray afterglow properties 34 h after the GRB are reminiscent of the afterglows of long GRBs, which are attributable to synchrotron emission from ultrarelativistic ejecta. We did not, however, detect a supernova, as found in most nearby long GRB afterglows, which suggests a different origin for the short GRBs.

A molecular gas-rich GRB host galaxy at the peak of cosmic star formation

NASA Astrophysics Data System (ADS)

Arabsalmani, M.; Le Floc'h, E.; Dannerbauer, H.; Feruglio, C.; Daddi, E.; Ciesla, L.; Charmandaris, V.; Japelj, J.; Vergani, S. D.; Duc, P.-A.; Basa, S.; Bournaud, F.; Elbaz, D.

2018-05-01

We report the detection of the CO(3-2) emission line from the host galaxy of gamma-ray burst (GRB) 080207 at z = 2.086. This is the first detection of molecular gas in emission from a GRB host galaxy beyond redshift 1. We find this galaxy to be rich in molecular gas with a mass of 1.1 × 10^{11} M_{{\\odot }} assuming αCO = 4.36 M_{{\\odot }} (K km s^{-1} pc^2)^{-1}. The molecular gas mass fraction of the galaxy is ˜0.5, typical of star-forming galaxies (SFGs) with similar stellar masses and redshifts. With an SFR_{FIR} of 260 M_{{\\odot }} yr^{-1}, we measure a molecular gas depletion time-scale of 0.43 Gyr, near the peak of the depletion time-scale distribution of SFGs at similar redshifts. Our findings are therefore in contradiction with the proposed molecular gas deficiency in GRB host galaxies. We argue that the reported molecular gas deficiency for GRB hosts could be the artefact of improper comparisons or neglecting the effect of the typical low metallicities of GRB hosts on the CO-to-molecular-gas conversion factor. We also compare the kinematics of the CO(3-2) emission line to that of the H α emission line from the host galaxy. We find the H α emission to have contributions from two separate components, a narrow and a broad one. The narrow component matches the CO emission well in velocity space. The broad component, with a full width at half-maximum of ˜1100 km s^{-1}, is separated by +390 km s^{-1} in velocity space from the narrow component. We speculate this broad component to be associated with a powerful outflow in the host galaxy or in an interacting system.

Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors.

PubMed

Vinberg, Frans; Peshenko, Igor V; Chen, Jeannie; Dizhoor, Alexander M; Kefalov, Vladimir J

2018-05-11

Light adaptation of photoreceptor cells is mediated by Ca 2+ -dependent mechanisms. In darkness, Ca 2+ influx through cGMP-gated channels into the outer segment of photoreceptors is balanced by Ca 2+ extrusion via Na + /Ca 2+ , K + exchangers (NCKXs). Light activates a G protein signaling cascade, which closes cGMP-gated channels and decreases Ca 2+ levels in photoreceptor outer segment because of continuing Ca 2+ extrusion by NCKXs. Guanylate cyclase-activating proteins (GCAPs) then up-regulate cGMP synthesis by activating retinal membrane guanylate cyclases (RetGCs) in low Ca 2+ This activation of RetGC accelerates photoresponse recovery and critically contributes to light adaptation of the nighttime rod and daytime cone photoreceptors. In mouse rod photoreceptors, GCAP1 and GCAP2 both contribute to the Ca 2+ -feedback mechanism. In contrast, only GCAP1 appears to modulate RetGC activity in mouse cones because evidence of GCAP2 expression in cones is lacking. Surprisingly, we found that GCAP2 is expressed in cones and can regulate light sensitivity and response kinetics as well as light adaptation of GCAP1-deficient mouse cones. Furthermore, we show that GCAP2 promotes cGMP synthesis and cGMP-gated channel opening in mouse cones exposed to low Ca 2+ Our biochemical model and experiments indicate that GCAP2 significantly contributes to the activation of RetGC1 at low Ca 2+ when GCAP1 is not present. Of note, in WT mouse cones, GCAP1 dominates the regulation of cGMP synthesis. We conclude that, under normal physiological conditions, GCAP1 dominates the regulation of cGMP synthesis in mouse cones, but if its function becomes compromised, GCAP2 contributes to the regulation of phototransduction and light adaptation of cones. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

PubMed Central

Cowley, Michael; Garfield, Alastair S.; Madon-Simon, Marta; Charalambous, Marika; Clarkson, Richard W.; Smalley, Matthew J.; Kendrick, Howard; Isles, Anthony R.; Parry, Aled J.; Carney, Sara; Oakey, Rebecca J.; Heisler, Lora K.; Moorwood, Kim; Wolf, Jason B.; Ward, Andrew

2014-01-01

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk. PMID:24586114

Unusual Central Engine Activity in the Double Burst GRB 110709B

NASA Technical Reports Server (NTRS)

Zhang, Bin-Bin; Burrows, David N.; Zhang, Bing; Meszaros, Peter; Stratta, Giulia; D'Elia, Valerio; Frederiks, Dmitry; Golenetskii, S.; Cummings, Jay R.; Wang, Xiang-Yu;

GRB/GW Association: Long-Short GRB Candidates, Time Lag, Measuring Gravitational Wave Velocity, and Testing Einstein’s Equivalence Principle

NASA Astrophysics Data System (ADS)

Li, Xiang; Hu, Yi-Ming; Fan, Yi-Zhong; Wei, Da-Ming

2016-08-01

Short-duration gamma-ray bursts (SGRBs) are widely believed to be powered by the mergers of compact binaries, such as binary neutron stars or possibly neutron star-black hole binaries. Though the prospect of detecting SGRBs with gravitational wave (GW) signals by the advanced Laser Interferometer Gravitational-Wave Observatory (LIGO)/VIRGO network is promising, no known SGRB has been found within the expected advanced LIGO/VIRGO sensitivity range for binary neutron star systems. We find, however, that the two long-short GRBs (GRB 060505 and GRB 060614) may be within the horizon of advanced GW detectors. In the upcoming era of GW astronomy, the merger origin of some long-short GRBs, as favored by the macronova signature displayed in GRB 060614, can be unambiguously tested. The model-dependent time lags between the merger and the onset of the prompt emission of the GRB are estimated. The comparison of such time lags between model predictions and the real data expected in the era of the GW astronomy would be helpful in revealing the physical processes taking place at the central engine (including the launch of the relativistic outflow, the emergence of the outflow from the dense material ejected during the merger, and the radiation of gamma rays). We also show that the speed of GWs, with or without a simultaneous test of Einstein’s equivalence principle, can be directly measured to an accuracy of ˜ 3× {10}-8 {cm} {{{s}}}-1 or even better in the advanced LIGO/VIRGO era.

A new gamma-ray burst classification scheme from GRB 060614.

PubMed

Gehrels, N; Norris, J P; Barthelmy, S D; Granot, J; Kaneko, Y; Kouveliotou, C; Markwardt, C B; Mészáros, P; Nakar, E; Nousek, J A; O'Brien, P T; Page, M; Palmer, D M; Parsons, A M; Roming, P W A; Sakamoto, T; Sarazin, C L; Schady, P; Stamatikos, M; Woosley, S E

2006-12-21

Gamma-ray bursts (GRBs) are known to come in two duration classes, separated at approximately 2 s. Long-duration bursts originate from star-forming regions in galaxies, have accompanying supernovae when these are near enough to observe and are probably caused by massive-star collapsars. Recent observations show that short-duration bursts originate in regions within their host galaxies that have lower star-formation rates, consistent with binary neutron star or neutron star-black hole mergers. Moreover, although their hosts are predominantly nearby galaxies, no supernovae have been so far associated with short-duration GRBs. Here we report that the bright, nearby GRB 060614 does not fit into either class. Its approximately 102-s duration groups it with long-duration GRBs, while its temporal lag and peak luminosity fall entirely within the short-duration GRB subclass. Moreover, very deep optical observations exclude an accompanying supernova, similar to short-duration GRBs. This combination of a long-duration event without an accompanying supernova poses a challenge to both the collapsar and the merging-neutron-star interpretations and opens the door to a new GRB classification scheme that straddles both long- and short-duration bursts.

Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.

PubMed

McDonald, Caleb B; Seldeen, Kenneth L; Deegan, Brian J; Bhat, Vikas; Farooq, Amjad

2011-01-01

A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3, and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 3(10) -helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. Copyright © 2010 John Wiley & Sons, Ltd.

Binding of the cSH3 Domain of Grb2 Adaptor to Two Distinct RXXK Motifs within Gab1 Docker Employs Differential Mechanisms

PubMed Central

McDonald, Caleb B.; Seldeen, Kenneth L.; Deegan, Brian J.; Bhat, Vikas; Farooq, Amjad

2010-01-01

A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3 and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 310-helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. PMID:21472810

FERMI Observations of High-Energy Gamma-Ray Emission from GRB 080825C

DOE PAGES

Abdo, A. A.; Ackermann, M.; Asano, K.; ...

2009-11-24

The Fermi Gamma-ray Space Telescope has opened a new high-energy window in the study of gamma-ray bursts (GRBs). Here in this paper, we present a thorough analysis of GRB 080825C, which triggered the Fermi Gamma-ray Burst Monitor (GBM), and was the first firm detection of a GRB by the Fermi Large Area Telescope (LAT). We discuss the LAT event selections, background estimation, significance calculations, and localization for Fermi GRBs in general and GRB 080825C in particular. We show the results of temporal and time-resolved spectral analysis of the GBM and LAT data. Finally, we also present some theoretical interpretation ofmore » GRB 080825C observations as well as some common features observed in other LAT GRBs.« less

GRB 020410: A Gamma-ray burst afterglow discovered by its supernova light

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

Levan, Andrew; Nugent, Peter; Fruchter, Andrew

2004-03-19

We present the discovery and monitoring of the optical transient (OT) associated with GRB 020410. The fading OT was found by Hubble Space Telescope (HST) observations taken 28 and 65 days after burst at a position consistent with the X-ray afterglow. Subsequent re-examination of early ground based observations revealed that a faint OT was present 6 hours after burst, confirming the source association with GRB 020410. A deep non-detection after one week requires that the OT re-brightened between day 7 and day 28, and further late time HST data taken approximately 100 days after burst imply that it is verymore » red (F{sub nu} proportional to nu-2.7). We compare both the flux and color of the excess with supernova models and show that the data are best explained by the presence of a Type I b/c supernova at a redshift z approx. equal 0.5, which occurred roughly coincident with the day of GRB.« less

HIGH-ENERGY EMISSION OF GRB 130427A: EVIDENCE FOR INVERSE COMPTON RADIATION

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

Fan, Yi-Zhong; Zhang, Fu-Wen; He, Hao-Ning

2013-10-20

A nearby superluminous burst GRB 130427A was simultaneously detected by six γ-ray space telescopes (Swift, the Fermi GLAST Burst Monitor (GBM)/Large Area Telescope, Konus-Wind, SPI-ACS/INTEGRAL, AGILE, and RHESSI) and by three RAPTOR full-sky persistent monitors. The isotropic γ-ray energy release is ∼10{sup 54} erg, rendering it the most powerful explosion among gamma-ray bursts (GRBs) with a redshift z ≤ 0.5. The emission above 100 MeV lasted about one day, and four photons are at energies greater than 40 GeV. We show that the count rate of 100 MeV-100 GeV emission may be mainly accounted for by the forward shock synchrotronmore » radiation and the inverse Compton radiation likely dominates at GeV-TeV energies. In particular, an inverse Compton radiation origin is favored for the ∼(95.3, 47.3, 41.4, 38.5, 32) GeV photons arriving at t ∼ (243, 256.3, 610.6, 3409.8, 34366.2) s after the trigger of Fermi-GBM. Interestingly, the external inverse Compton scattering of the prompt emission (the second episode, i.e., t ∼ 120-260 s) by the forward-shock-accelerated electrons is expected to produce a few γ-rays at energies above 10 GeV, while five were detected in the same time interval. A possible unified model for the prompt soft γ-ray, optical, and GeV emission of GRB 130427A, GRB 080319B, and GRB 090902B is outlined. Implications of the null detection of >1 TeV neutrinos from GRB 130427A by IceCube are discussed.« less

Synchrotron radiation and diffusive shock acceleration - A short review and GRB perspective

NASA Astrophysics Data System (ADS)

Karlica, Mile

2015-12-01

In this talk we present the sponge" model and its possible implications on the GRB afterglow light curves. "Sponge" model describes source of GRB afterglow radiation as fragmented GRB ejecta where bubbles move through the rarefied medium. In the first part of the talk a short introduction to synchrotron radiation and Fermi acceleration was presented. In the assumption that X-ray luminosity of GRB afterglow phase comes from the kinetic energy losses of clouds in ejecta medium radiated as synchrotron radiation we solved currently very simple equation of motion to find which combination of cloud and medium regime describes the afterglow light curve the best. We proposed for the first step to watch simple combinations of expansion regimes for both bubbles and surrounding medium. The closest case to the numerical fit of GRB 150403A with time power law index k = 1.38 is the combination of constant bubbles and Sedov like expanding medium with time power law index k = 1.25. Of course the question of possible mixture of variuos regime combinations is still open within this model.

Optical polarimetric observations of GRB prompt emissions by MASTER robots-telescopes net.

NASA Astrophysics Data System (ADS)

Gorbovskoy, Evgeny; Lipunov, Vladimir; Kornilov, Victor; Shatskij, Nikolaj; Kuvshi-Nov, Dmitry; Tyurina, Nataly; Belinski, Alexander; Krylov, Alexander; Balanutsa, Pavel; Chazov, Vadim; Kuznetsov, Artem; Zimnuhov, Dmitry; Balanutsa, Pavel; Kortunov, Petr; Sankovich, Anatoly; Tlatov, An-Drey; Parkhomenko, A.; Krushinsky, Vadim; Zalozhnyh, Ivan; Popov, A.; Kopytova, Taisia; Ivanov, Kirill; Yazev, Sergey; Yurkov, Vladimir

The main goal of the MASTER-Net project is to produce a unique fast sky survey with all sky observed over a single night down to a limiting magnitude of 19 -20mag. Such a survey will make it possible to address a number of fundamental problems: search for dark energy via the discovery and photometry of supernovas (including SNIa), search for exoplanets, microlensing effects, discovery of minor bodies in the Solar System and space-junk monitoring. All MASTER telescopes can be guided by alerts, and we plan to observe prompt optical emission from gamma-ray bursts synchronously in several filters and in several polarization planes. Observations on telescopes capable to observ polarisation of GRB prompt emission have been begun in the summer of 2009. Since summer of 2009 an observations of several GRB have been made. In particular for GRB0910 and GRB091127 optical polarisation has been measured. So, for GRB091127 which supervision have begun all through 91 sec polarisation at level of several tens percent has been registered. (GCN 10231, GCN 10052, GCN 10203)

Deep Photometry of GRB 041006 Afterglow: Hypernova Bump at Redshift z = 0.716

NASA Astrophysics Data System (ADS)

Stanek, K. Z.; Garnavich, P. M.; Nutzman, P. A.; Hartman, J. D.; Garg, A.; Adelberger, K.; Berlind, P.; Bonanos, A. Z.; Calkins, M. L.; Challis, P.; Gaudi, B. S.; Holman, M. J.; Kirshner, R. P.; McLeod, B. A.; Osip, D.; Pimenova, T.; Reiprich, T. H.; Romanishin, W.; Spahr, T.; Tegler, S. C.; Zhao, X.

2005-06-01

We present deep optical photometry of the afterglow of gamma-ray burst (GRB) 041006 and its associated hypernova obtained over 65 days after detection (55 R-band epochs on 10 different nights). Our early data (t<4 days) joined with published GCN data indicate a steepening decay, approaching Fν~t-0.6 at early times (t<<1 day) and Fν~t-1.3 at late times. The break at tb=0.16+/-0.04 days is the earliest reported jet break among all GRB afterglows. During our first night, we obtained 39 exposures spanning 2.15 hr from 0.62 to 0.71 days after the burst that reveal a smooth afterglow, with an rms deviation of 0.024 mag from the local power-law fit, consistent with photometric errors. After t~4 days, the decay slows considerably, and the light curve remains approximately flat at R~24 mag for a month before decaying by another magnitude to reach R~25 mag 2 months after the burst. This ``bump'' is well fit by a k-corrected light curve of supernova SN 1998bw, but only if stretched by a factor of 1.38 in time. In comparison with the other GRB-related SN bumps, GRB 041006 stakes out new parameter space for GRBs/SNe, with a very bright and significantly stretched late-time SN light curve. Within a small sample of fairly well observed GRB/SN bumps, we see a hint of a possible correlation between their peak luminosity and their ``stretch factor,'' broadly similar to the well-studied Phillips relation for the Type Ia supernovae. Based on data from the MMT Observatory 6.5 m telescope, the 1.8 m Vatican Advanced Technology Telescope, the Magellan 6.5 m Baade and Clay telescopes, and the Keck II 10 m telescope.

CONSTRAINING THE GRB-MAGNETAR MODEL BY MEANS OF THE GALACTIC PULSAR POPULATION

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

Rea, N.; Gullón, M.; Pons, J. A.

2015-11-10

A large fraction of Gamma-ray bursts (GRBs) displays an X-ray plateau phase within <10{sup 5} s from the prompt emission, proposed to be powered by the spin-down energy of a rapidly spinning newly born magnetar. In this work we use the properties of the Galactic neutron star population to constrain the GRB-magnetar scenario. We re-analyze the X-ray plateaus of all Swift GRBs with known redshift, between 2005 January and 2014 August. From the derived initial magnetic field distribution for the possible magnetars left behind by the GRBs, we study the evolution and properties of a simulated GRB-magnetar population using numericalmore » simulations of magnetic field evolution, coupled with Monte Carlo simulations of Pulsar Population Synthesis in our Galaxy. We find that if the GRB X-ray plateaus are powered by the rotational energy of a newly formed magnetar, the current observational properties of the Galactic magnetar population are not compatible with being formed within the GRB scenario (regardless of the GRB type or rate at z = 0). Direct consequences would be that we should allow the existence of magnetars and “super-magnetars” having different progenitors, and that Type Ib/c SNe related to Long GRBs form systematically neutron stars with higher initial magnetic fields. We put an upper limit of ≤16 “super-magnetars” formed by a GRB in our Galaxy in the past Myr (at 99% c.l.). This limit is somewhat smaller than what is roughly expected from Long GRB rates, although the very large uncertainties do not allow us to draw strong conclusion in this respect.« less

The GRB All-sky Spectrometer Experiment I: Instrument Overview and Science Drivers

NASA Astrophysics Data System (ADS)

Martinot, Zachary; Voigt, Elana; Banks, Zachary; Pober, Jonathan; Morales, Miguel F.

2015-01-01

The GRB All-sky Spectrometer Experiment (GASE) is an experiment designed to detect low frequency highly dispersed radio emission in the afterglow of a GRB. The detection of such a signal could provide a probe of IGM density as well as the conditions near the source of a GRB. The instrument used is an eight-element array of dipole antennas located on the University of Washington campus. This poster will further elaborate the design of the instrument and its scientific goals.

Adaptive Local Realignment of Protein Sequences.

PubMed

DeBlasio, Dan; Kececioglu, John

2018-06-11

While mutation rates can vary markedly over the residues of a protein, multiple sequence alignment tools typically use the same values for their scoring-function parameters across a protein's entire length. We present a new approach, called adaptive local realignment, that in contrast automatically adapts to the diversity of mutation rates along protein sequences. This builds upon a recent technique known as parameter advising, which finds global parameter settings for an aligner, to now adaptively find local settings. Our approach in essence identifies local regions with low estimated accuracy, constructs a set of candidate realignments using a carefully-chosen collection of parameter settings, and replaces the region if a realignment has higher estimated accuracy. This new method of local parameter advising, when combined with prior methods for global advising, boosts alignment accuracy as much as 26% over the best default setting on hard-to-align protein benchmarks, and by 6.4% over global advising alone. Adaptive local realignment has been implemented within the Opal aligner using the Facet accuracy estimator.

Detection of the thermal component in GRB 160107A

NASA Astrophysics Data System (ADS)

Kawakubo, Yuta; Sakamoto, Takanori; Nakahira, Satoshi; Yamaoka, Kazutaka; Serino, Motoko; saoka, Yoichi; Cherry, Michael L.; Matsukawa, Shohei; Mori, Masaki; Nakagawa, Yujin; Ozawa, Shunsuke; Penacchioni, Ana V.; Ricciarini, Sergio B.; Tezuka, Akira; Torii, Shoji; Yamada, Yusuke; Yoshida, Atsumasa

2018-01-01

We present the detection of a blackbody component in gamma-ray burst GRB 160107A emission by using the combined spectral data of the CALET Gamma-ray Burst Monitor (CGBM) and the MAXI Gas Slit Camera (GSC). MAXI/GSC detected the emission ˜45 s prior to the main burst episode observed by the CGBM. The MAXI/GSC and the CGBM spectrum of this prior emission period is fitted well by a blackbody with temperature 1.0^{+0.3}_{-0.2} keV plus a power law with a photon index of -1.6 ± 0.3. We discuss the radius of the photospheric emission and the main burst emission based on the observational properties. We stress the importance of coordinated observations via various instruments collecting high-quality data over a broad energy coverage in order to understand the GRB prompt emission mechanism.

Jet or Shock Breakout? The Low-Luminosity GRB 060218

NASA Astrophysics Data System (ADS)

Irwin, Christopher; Chevalier, Roger

2016-01-01

We consider a model for the long-duration, low-luminosity gamma-ray burst GRB 060218 that plausibly accounts for multiwavelength observations to day 20. The components of our model are: (1) a long-lived (tj ~ 3000 s) central engine and accompanying low-luminosity (Lj ~ 1045 erg s-1), mildly relativistic jet; (2) a low-mass (~ 10-2 Msun) envelope surrounding the progenitor star; and (3) a modest amount of dust (AV ~ 0.1) in the circumstellar or interstellar environment. Blackbody emission from the transparency radius in a low-power jet outflow can fit the prompt thermal X-ray emission, and the prompt nonthermal X-rays and γ-rays may be produced via Compton scattering of thermal photons from hot leptons in the jet interior or the external shocks. The later mildly relativistic phase of this outflow can produce the radio emission via synchrotron radiation from the forward shock. Meanwhile, interaction of the associated SN 2006aj with a circumstellar envelope extending to ~ 1013 cm can explain the early optical peak. The X-ray afterglow can be interpreted as a light echo of the prompt emission from dust at ~ 30 pc. Our model is a plausible alternative to that of Nakar, who recently proposed shock breakout of a jet smothered by an extended envelope as the source of prompt emission. Both our results and Nakar's suggest that ultra-long bursts such as GRB 060218 and GRB 100316D may originate from unusual progenitors with extended circumstellar envelopes, and that a jet is necessary to decouple the prompt high-energy emission from the supernova.

Wind-Interaction Models for the Early Afterglows of Gamma-Ray Bursts: The Case of GRB 021004

NASA Astrophysics Data System (ADS)

Li, Zhi-Yun; Chevalier, Roger A.

2003-06-01

Wind-interaction models for gamma-ray burst (GRB) afterglows predict that the optical emission from the reverse shock drops below that from the forward shock within hundreds of seconds of the burst. The typical frequency νm of the synchrotron emission from the forward shock passes through the optical band typically on a timescale of minutes to hours. Before the passage of νm, the optical flux evolves as t-1/4, and after the passage, the decay steepens to t-(3p-2)/4, where p is the exponent for the assumed power-law energy distribution of nonthermal electrons and is typically ~2. The steepening in the slope of temporal decay should be readily identifiable in the early afterglow light curves. We propose that such a steepening was observed in the R-band light curve of GRB 021004 around day 0.1. Available data at several radio frequencies are consistent with this interpretation, as are the X-ray observations around day 1. The early evolution of GRB 021004 contrasts with that of GRB 990123, which can be described by emission from interaction with a constant density medium.

Arabinogalactan Proteins Are Involved in Salt-Adaptation and Vesicle Trafficking in Tobacco by-2 Cell Cultures

PubMed Central

Olmos, Enrique; García De La Garma, Jesús; Gomez-Jimenez, Maria C.; Fernandez-Garcia, Nieves

2017-01-01

Arabinogalactan proteins (AGPs) are a highly diverse family of glycoproteins that are commonly found in most plant species. However, little is known about the physiological and molecular mechanisms of their function. AGPs are involved in different biological processes such as cell differentiation, cell expansion, tissue development and somatic embryogenesis. AGPs are also involved in abiotic stress response such as salinity modulating cell wall expansion. In this study, we describe how salt-adaptation in tobacco BY-2 cell cultures induces important changes in arabinogalactan proteins distribution and contents. Using the immuno-dot blot technique with different anti-AGP antibodies (JIM13, JIM15, and others), we observed that AGPs were highly accumulated in the culture medium of salt-adapted tobacco cells, probably due to the action of phospholipases. We located these AGP epitopes using immunogold labeling in the cytoplasm associated to the endoplasmic reticulum, the golgi apparatus, and vesicles, plasma membrane and tonoplast. Our results show that salt-adaptation induced a significant reduction of the cytoplasm, plasma membrane and tonoplast content of these epitopes. Yariv reagent was added to the control and salt-adapted tobacco cell cultures, leading to cell death induction in control cells but not in salt-adapted cells. Ultrastructural and immunogold labeling revealed that cell death induced by Yariv reagent in control cells was due to the interaction of Yariv reagent with the AGPs linked to the plasma membranes. Finally, we propose a new function of AGPs as a possible sodium carrier through the mechanism of vesicle trafficking from the apoplast to the vacuoles in salt-adapted tobacco BY-2 cells. This mechanism may contribute to sodium homeostasis during salt-adaptation to high saline concentrations. PMID:28676820

Arabinogalactan Proteins Are Involved in Salt-Adaptation and Vesicle Trafficking in Tobacco by-2 Cell Cultures.

PubMed

Olmos, Enrique; García De La Garma, Jesús; Gomez-Jimenez, Maria C; Fernandez-Garcia, Nieves

2017-01-01

Arabinogalactan proteins (AGPs) are a highly diverse family of glycoproteins that are commonly found in most plant species. However, little is known about the physiological and molecular mechanisms of their function. AGPs are involved in different biological processes such as cell differentiation, cell expansion, tissue development and somatic embryogenesis. AGPs are also involved in abiotic stress response such as salinity modulating cell wall expansion. In this study, we describe how salt-adaptation in tobacco BY-2 cell cultures induces important changes in arabinogalactan proteins distribution and contents. Using the immuno-dot blot technique with different anti-AGP antibodies (JIM13, JIM15, and others), we observed that AGPs were highly accumulated in the culture medium of salt-adapted tobacco cells, probably due to the action of phospholipases. We located these AGP epitopes using immunogold labeling in the cytoplasm associated to the endoplasmic reticulum, the golgi apparatus, and vesicles, plasma membrane and tonoplast. Our results show that salt-adaptation induced a significant reduction of the cytoplasm, plasma membrane and tonoplast content of these epitopes. Yariv reagent was added to the control and salt-adapted tobacco cell cultures, leading to cell death induction in control cells but not in salt-adapted cells. Ultrastructural and immunogold labeling revealed that cell death induced by Yariv reagent in control cells was due to the interaction of Yariv reagent with the AGPs linked to the plasma membranes. Finally, we propose a new function of AGPs as a possible sodium carrier through the mechanism of vesicle trafficking from the apoplast to the vacuoles in salt-adapted tobacco BY-2 cells. This mechanism may contribute to sodium homeostasis during salt-adaptation to high saline concentrations.

Implications for the Origin of GRB 051103 from LIGO Observations

NASA Astrophysics Data System (ADS)

Abadie, J.; Abbott, B. P.; Abbott, T. D.; Abbott, R.; Abernathy, M.; Adams, C.; Adhikari, R.; Affeldt, C.; Ajith, P.; Allen, B.; Allen, G. S.; Amador Ceron, E.; Amariutei, D.; Amin, R. S.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Arain, M. A.; Araya, M. C.; Aston, S. M.; Atkinson, D.; Aufmuth, P.; Aulbert, C.; Aylott, B. E.; Babak, S.; Baker, P.; Ballmer, S.; Barker, D.; Barnum, S.; Barr, B.; Barriga, P.; Barsotti, L.; Barton, M. A.; Bartos, I.; Bassiri, R.; Bastarrika, M.; Bauchrowitz, J.; Behnke, B.; Bell, A. S.; Belopolski, I.; Benacquista, M.; Bertolini, A.; Betzwieser, J.; Beveridge, N.; Beyersdorf, P. T.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Biswas, R.; Black, E.; Blackburn, J. K.; Blackburn, L.; Blair, D.; Bland, B.; Bock, O.; Bodiya, T. P.; Bogan, C.; Bondarescu, R.; Bork, R.; Born, M.; Bose, S.; Boyle, M.; Brady, P. R.; Braginsky, V. B.; Brau, J. E.; Breyer, J.; Bridges, D. O.; Brinkmann, M.; Britzger, M.; Brooks, A. F.; Brown, D. A.; Brummitt, A.; Buonanno, A.; Burguet-Castell, J.; Burmeister, O.; Byer, R. L.; Cadonati, L.; Camp, J. B.; Campsie, P.; Cannizzo, J.; Cannon, K.; Cao, J.; Capano, C.; Caride, S.; Caudill, S.; Cavaglia, M.; Cepeda, C.; Chalermsongsak, T.; Chalkley, E.; Charlton, P.; Chelkowski, S.; Chen, Y.; Christensen, N.; Chua, S. S. Y.; Chung, S.; Chung, C. T. Y.; Clara, F.; Clark, D.; Clark, J.; Clayton, J. H.; Conte, R.; Cook, D.; Corbitt, T. R. C.; Cornish, N.; Costa, C. A.; Coughlin, M.; Coward, D. M.; Coyne, D. C.; Creighton, J. D. E.; Creighton, T. D.; Cruise, A. M.; Cumming, A.; Cunningham, L.; Culter, R. M.; Dahl, K.; Danilishin, S. L.; Dannenberg, R.; Danzmann, K.; Das, K.; Daudert, B.; Daveloza, H.; Davies, G.; Daw, E. J.; Dayanga, T.; DeBra, D.; Degallaix, J.; Dent, T.; Dergachev, V.; DeRosa, R.; DeSalvo, R.; Dhurandhar, S.; Di Palma, I.; Díaz, M.; Donovan, F.; Dooley, K. L.; Dorsher, S.; Douglas, E. S. D.; Drever, R. W. P.; Driggers, J. C.; Dumas, J.-C.; Dwyer, S.; Eberle, T.; Edgar, M.; Edwards, M.; Effler, A.; Ehrens, P.; Engel, R.; Etzel, T.; Evans, M.; Evans, T.; Factourovich, M.; Fairhurst, S.; Fan, Y.; Farr, B. F.; Fazi, D.; Fehrmann, H.; Feldbaum, D.; Finn, L. S.; Flanigan, M.; Foley, S.; Forsi, E.; Fotopoulos, N.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Friedrich, D.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Garcia, J.; Garofoli, J. A.; Gholami, I.; Ghosh, S.; Giaime, J. A.; Giampanis, S.; Giardina, K. D.; Gill, C.; Goetz, E.; Goggin, L. M.; González, G.; Gorodetsky, M. L.; Goßler, S.; Graef, C.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Grosso, R.; Grote, H.; Grunewald, S.; Guido, C.; Gupta, R.; Gustafson, E. K.; Gustafson, R.; Hage, B.; Hallam, J. M.; Hammer, D.; Hammond, G.; Hanks, J.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G. M.; Harry, I. W.; Harstad, E. D.; Hartman, M. T.; Haughian, K.; Hayama, K.; Heefner, J.; Hendry, M. A.; Heng, I. S.; Heptonstall, A. W.; Herrera, V.; Hewitson, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Holt, K.; Hong, T.; Hooper, S.; Hosken, D. J.; Hough, J.; Howell, E. J.; Hughey, B.; Husa, S.; Huttner, S. H.; Ingram, D. R.; Inta, R.; Isogai, T.; Ivanov, A.; Johnson, W. W.; Jones, D. I.; Jones, G.; Jones, R.; Ju, L.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kanner, J. B.; Katsavounidis, E.; Katzman, W.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kells, W.; Kelner, M.; Keppel, D. G.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, N.; Kim, H.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kondrashov, V.; Kopparapu, R.; Koranda, S.; Korth, W. Z.; Kozak, D.; Kringel, V.; Krishnamurthy, S.; Krishnan, B.; Kuehn, G.; Kumar, R.; Kwee, P.; Landry, M.; Lantz, B.; Lastzka, N.; Lazzarini, A.; Leaci, P.; Leong, J.; Leonor, I.; Li, J.; Lindquist, P. E.; Lockerbie, N. A.; Lodhia, D.; Lormand, M.; Lu, P.; Luan, J.; Lubinski, M.; Lück, H.; Lundgren, A. P.; Macdonald, E.; Machenschalk, B.; MacInnis, M.; Mageswaran, M.; Mailand, K.; Mandel, I.; Mandic, V.; Marandi, A.; Márka, S.; Márka, Z.; Maros, E.; Martin, I. W.; Martin, R. M.; Marx, J. N.; Mason, K.; Matichard, F.; Matone, L.; Matzner, R. A.; Mavalvala, N.; McCarthy, R.; McClelland, D. E.; McGuire, S. C.; McIntyre, G.; McIver, J.; McKechan, D. J. A.; Meadors, G.; Mehmet, M.; Meier, T.; Melatos, A.; Melissinos, A. C.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyer, M. S.; Miao, H.; Miller, J.; Mino, Y.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Miyakawa, O.; Moe, B.; Moesta, P.; Mohanty, S. D.; Moraru, D.; Moreno, G.; Mossavi, K.; Mow-Lowry, C. M.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Müller-Ebhardt, H.; Munch, J.; Murphy, D.; Murray, P. G.; Nash, T.; Nawrodt, R.; Nelson, J.; Newton, G.; Nishizawa, A.; Nolting, D.; Nuttall, L.; O'Reilly, B.; O'Shaughnessy, R.; Ochsner, E.; O'Dell, J.; Ogin, G. H.; Oldenburg, R. G.; Osthelder, C.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Page, A.; Pan, Y.; Pankow, C.; Papa, M. A.; Patel, P.; Pedraza, M.; Pekowsky, L.; Penn, S.; Peralta, C.; Perreca, A.; Phelps, M.; Pickenpack, M.; Pinto, I. M.; Pitkin, M.; Pletsch, H. J.; Plissi, M. V.; Podkaminer, J.; Pöld, J.; Postiglione, F.; Predoi, V.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prix, R.; Prokhorov, L.; Puncken, O.; Quetschke, V.; Raab, F. J.; Radkins, H.; Raffai, P.; Rakhmanov, M.; Ramet, C. R.; Rankins, B.; Mohapatra, S. R. P.; Raymond, V.; Redwine, K.; Reed, C. M.; Reed, T.; Reid, S.; Reitze, D. H.; Riesen, R.; Riles, K.; Roberts, P.; Robertson, N. A.; Robinson, C.; Robinson, E. L.; Roddy, S.; Rollins, J.; Romano, J. D.; Romie, J. H.; Röver, C.; Rowan, S.; Rüdiger, A.; Ryan, K.; Sakata, S.; Sakosky, M.; Salemi, F.; Salit, M.; Sammut, L.; Sancho de la Jordana, L.; Sandberg, V.; Sannibale, V.; Santamaría, L.; Santiago-Prieto, I.; Santostasi, G.; Saraf, S.; Sathyaprakash, B. S.; Sato, S.; Saulson, P. R.; Savage, R.; Schilling, R.; Schlamminger, S.; Schnabel, R.; Schofield, R. M. S.; Schulz, B.; Schutz, B. F.; Schwinberg, P.; Scott, J.; Scott, S. M.; Searle, A. C.; Seifert, F.; Sellers, D.; Sengupta, A. S.; Sergeev, A.; Shaddock, D. A.; Shaltev, M.; Shapiro, B.; Shawhan, P.; Shihan Weerathunga, T.; Shoemaker, D. H.; Sibley, A.; Siemens, X.; Sigg, D.; Singer, A.; Singer, L.; Sintes, A. M.; Skelton, G.; Slagmolen, B. J. J.; Slutsky, J.; Smith, R.; Smith, J. R.; Smith, M. R.; Smith, N. D.; Somiya, K.; Sorazu, B.; Soto, J.; Speirits, F. C.; Stein, A. J.; Steinlechner, J.; Steinlechner, S.; Steplewski, S.; Stefszky, M.; Stochino, A.; Stone, R.; Strain, K. A.; Strigin, S.; Stroeer, A. S.; Stuver, A. L.; Summerscales, T. Z.; Sung, M.; Susmithan, S.; Sutton, P. J.; Szokoly, G. P.; Talukder, D.; Tanner, D. B.; Tarabrin, S. P.; Taylor, J. R.; Taylor, R.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Thüring, A.; Tokmakov, K. V.; Torres, C.; Torrie, C. I.; Traylor, G.; Trias, M.; Tseng, K.; Ugolini, D.; Urbanek, K.; Vahlbruch, H.; Vaishnav, B.; Vallisneri, M.; Van Den Broeck, C.; van der Sluys, M. V.; van Veggel, A. A.; Vass, S.; Vaulin, R.; Vecchio, A.; Veitch, J.; Veitch, P. J.; Veltkamp, C.; Villar, A. E.; Vorvick, C.; Vyachanin, S. P.; Waldman, S. J.; Wallace, L.; Wanner, A.; Ward, R. L.; Wei, P.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Wen, S.; Wessels, P.; West, M.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D.; Whiting, B. F.; Wilkinson, C.; Willems, P. A.; Williams, H. R.; Williams, L.; Willke, B.; Winkelmann, L.; Winkler, W.; Wipf, C. C.; Wiseman, A. G.; Woan, G.; Wooley, R.; Worden, J.; Yablon, J.; Yakushin, I.; Yamamoto, K.; Yamamoto, H.; Yang, H.; Yeaton-Massey, D.; Yoshida, S.; Yu, P.; Zanolin, M.; Zhang, L.; Zhang, Z.; Zhao, C.; Zotov, N.; Zucker, M. E.; Zweizig, J.; LIGO Collaboration; Bizouard, M. A.; Dietz, A.; Guidi, G. M.; Was, M.

2012-08-01

We present the results of a LIGO search for gravitational waves (GWs) associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst (GRB) whose electromagnetically determined sky position is coincident with the spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for short-hard GRBs include compact object mergers and soft gamma repeater (SGR) giant flares. A merger progenitor would produce a characteristic GW signal that should be detectable at a distance of M81, while GW emission from an SGR is not expected to be detectable at that distance. We found no evidence of a GW signal associated with GRB 051103. Assuming weakly beamed γ-ray emission with a jet semi-angle of 30°, we exclude a binary neutron star merger in M81 as the progenitor with a confidence of 98%. Neutron star-black hole mergers are excluded with >99% confidence. If the event occurred in M81, then our findings support the hypothesis that GRB 051103 was due to an SGR giant flare, making it one of the most distant extragalactic magnetars observed to date.

General Features of GRB 030329 in the EMBH Model

NASA Astrophysics Data System (ADS)

Bernardini, Maria Grazia; Bianco, Carlo Luciano; Ruffini, Remo; Xue, She-Sheng; Chardonnet, Pascal; Fraschetti, Federico

2006-02-01

GRB 030329 is considered within the EMBH model. We determine the three free parameters and deduce its luminosity in given energy bands comparing it with the observations. The observed substructures are compared with the predictions of the model: by applying the result that substructures observed in the extended afterglow peak emission (E-APE) do indeed originate in the collision of the accelerated baryonic matter (ABM) pulse with the inhomogeneities in the interstellar medium around the black-hole, masks of density inhomogeneities are considered in order to reproduce the observed temporal substructures. The induced supernova concept is applied to this system and the general consequences that we are witnessing are the formation of a cosmological thriptych of a black hole originating the GRB 030329, the supernova SN2003dh and a young neutron star. Analogies to the system GRB 980425-SN1998bw are outlined.

Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

PubMed

Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

1993-06-25

Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

Phosphorylation of the Grb2- and phosphatidylinositol 3-kinase p85-binding p36/38 by Syk in Lck-negative T cells.

PubMed

von Willebrand, M; Williams, S; Tailor, P; Mustelin, T

1998-06-01

Activation of the mitogen-activated protein kinase (MAPK) pathway by the T-cell antigen receptor (TCR) in T cells involves a positive role for phosphatidylinositol 3-kinase (PI3K) activity. We recently reported that over-expression of the Syk protein tyrosine kinase in the Lck-negative JCaM1 cells enabled the TCR to induce a normal activation of the Erk2 MAPK and enhanced transcription of a reporter gene driven by the nuclear factor of activated T cells and AP-1. Because this system allows us to analyse the targets for Syk in receptor-mediated signalling, we examined the role of PI3K in signalling events between the TCR-regulated Syk and the downstream activation of Erk2. We report that inhibition of PI3K by wortmannin or an inhibitory p85 construct, p85deltaiSH2, reduced the TCR-induced Syk-dependent activation of Erk2, as well as the appearance of phospho-Erk and phospho-Mek. At the same time, expression of Syk resulted in the activation-dependent phosphorylation of three proteins that bound to the src homology 2 (SH2) domains of PI3K p85. The strongest of these bands had an apparent molecular mass of 36-38 kDa on SDS gels, and it was quantitatively removed from the lysates by adsorption to a fusion protein containing the SH2 domain of Grb2. The appearance of this band was Syk dependent, and it was seen only upon triggering of the TCR complex. Thus, p36/38 was phosphorylated by Syk or a Syk-regulated kinase, and this protein may provide a link to the recruitment and activation of PI3K, as well as to the Ras-MAPK pathway, in TCR-triggered T cells.

Wide-Field Gamma-Spectrometer BDRG: GRB Monitor On-Board the Lomonosov Mission

NASA Astrophysics Data System (ADS)

Svertilov, S. I.; Panasyuk, M. I.; Bogomolov, V. V.; Amelushkin, A. M.; Barinova, V. O.; Galkin, V. I.; Iyudin, A. F.; Kuznetsova, E. A.; Prokhorov, A. V.; Petrov, V. L.; Rozhkov, G. V.; Yashin, I. V.; Gorbovskoy, E. S.; Lipunov, V. M.; Park, I. H.; Jeong, S.; Kim, M. B.

2018-02-01

The study of GRB prompt emissions (PE) is one of the main goals of the Lomonosov space mission. The payloads of the GRB monitor (BDRG) with the wide-field optical cameras (SHOK) and the ultra-fast flash observatory (UFFO) onboard the Lomonosov satellite are intended for the observation of GRBs, and in particular, their prompt emissions. The BDRG gamma-ray spectrometer is designed to obtain the temporal and spectral information of GRBs in the energy range of 10-3000 keV as well as to provide GRB triggers on several time scales (10 ms, 1 s and 20 s) for ground and space telescopes, including the UFFO and SHOK. The BDRG instrument consists of three identical detector boxes with axes shifted by 90° from each other. This configuration allows us to localize a GRB source in the sky with an accuracy of ˜ 2°. Each BDRG box contains a phoswich NaI(Tl)/CsI(Tl) scintillator detector. A thick CsI(Tl) crystal in size of \\varnothing 130 × 17 mm is placed underneath the NaI(Tl) as an active shield in the soft energy range and as the main detector in the hard energy range. The ratio of the CsI(Tl) to NaI(Tl) event rates at varying energies can be employed as an independent metric to distinguish legitimate GRB signals from false positives originating from electrons in near-Earth vicinities. The data from three detectors are collected in a BA BDRG information unit, which generates a GRB trigger and a set of data frames in output format. The scientific data output is ˜ 500 Mb per day, including ˜ 180 Mb of continuous data for events with durations in excess of 100 ms for 16 channels in each detector, detailed energy spectra, and sets of frames with ˜ 5 Mb of detailed information for each burst-like event. A number of pre-flight tests including those for the trigger algorithm and calibration were carried out to confirm the reliability of the BDRG for operation in space.

A Missing-link in the Supernova-GRB Connection: The Case of SN 2012ap

NASA Astrophysics Data System (ADS)

Chakraborti, Sayan; Soderberg, Alicia; Chomiuk, Laura; Kamble, Atish; Yadav, Naveen; Ray, Alak; Hurley, Kevin; Margutti, Raffaella; Milisavljevic, Dan; Bietenholz, Michael; Brunthaler, Andreas; Pignata, Giuliano; Pian, Elena; Mazzali, Paolo; Fransson, Claes; Bartel, Norbert; Hamuy, Mario; Levesque, Emily; MacFadyen, Andrew; Dittmann, Jason; Krauss, Miriam; Briggs, M. S.; Connaughton, V.; Yamaoka, K.; Takahashi, T.; Ohno, M.; Fukazawa, Y.; Tashiro, M.; Terada, Y.; Murakami, T.; Goldsten, J.; Barthelmy, S.; Gehrels, N.; Cummings, J.; Krimm, H.; Palmer, D.; Golenetskii, S.; Aptekar, R.; Frederiks, D.; Svinkin, D.; Cline, T.; Mitrofanov, I. G.; Golovin, D.; Litvak, M. L.; Sanin, A. B.; Boynton, W.; Fellows, C.; Harshman, K.; Enos, H.; von Kienlin, A.; Rau, A.; Zhang, X.; Savchenko, V.

2015-06-01

Gamma-ray bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly, usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However, supernovae with heavy ejecta can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for a few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. However, the ejecta from SN 2009bb was baryon loaded and in nearly free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than one-sixth of the fluence from GRB 980425. This shows for the first time that central engines in SNe Ic, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.

Search for GRB related prompt optical emission and other fast varying objects with ``Pi of the Sky'' detector

NASA Astrophysics Data System (ADS)

Ćwiok, M.; Dominik, W.; Małek, K.; Mankiewicz, L.; Mrowca-Ciułacz, J.; Nawrocki, K.; Piotrowski, L. W.; Sitek, P.; Sokołowski, M.; Wrochna, G.; Żarnecki, A. F.

2007-06-01

Experiment “Pi of the Sky” is designed to search for prompt optical emission from GRB sources. 32 CCD cameras covering 2 steradians will monitor the sky continuously. The data will be analysed on-line in search for optical flashes. The prototype with 2 cameras operated at Las Campanas (Chile) since 2004 has recognised several outbursts of flaring stars and has given limits for a few GRB.

Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor

PubMed Central

Landry, Mélissa; Pomerleau, Véronique; Saucier, Caroline

2016-01-01

Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein isoforms encoded by the ShcA (Shc) gene. Structure–function studies have unveiled critical roles for p52Shc-dependent signalling pathways in Met-regulated biological functions. The molecular basis of the interaction between the Met and p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc. In the present study, co-immunoprecipitation assays were performed in human embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and p66Shc mutants, in order to define the molecular determinants involved in mediating Met–p66Shc interaction. Our results show that p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding modules, and its collagen homology domain 2 (CH2) region, exert negative constraints. In contrast, p66Shc interaction with the activated Met depends mainly on the integrity of its PTB domain, and to a lesser extent of its SH2 domain. Even though not required for the recruitment of p66Shc, tyrosine phosphorylation of p66Shc by activated Met enhances these interactions by mechanisms not reliant on the integrity of the Met multisubstrate-binding site. In turn, this increases phosphotyrosine-dependent p66Shc–Grb2–Gab1 complex formation away from the receptor, while blocking Grb2 and Gab1 recruitment to activated Met. In conclusion, we identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor. PMID:27048591

The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor.

PubMed

Ingham, R J; Holgado-Madruga, M; Siu, C; Wong, A J; Gold, M R

1998-11-13

Gab1 is a member of the docking/scaffolding protein family which includes IRS-1, IRS-2, c-Cbl, p130(cas), and p62(dok). These proteins contain a variety of protein-protein interaction motifs including multiple tyrosine residues that when phosphorylated can act as binding sites for Src homology 2 (SH2) domain-containing signaling proteins. We show in the RAMOS human B cell line that Gab1 is tyrosine-phosphorylated in response to B cell antigen receptor (BCR) engagement. Moreover, tyrosine phosphorylation of Gab1 correlated with the binding of several SH2-containing signaling proteins to Gab1 including Shc, Grb2, phosphatidylinositol 3-kinase, and the SHP-2 tyrosine phosphatase. Far Western analysis showed that the SH2 domains of Shc, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase could bind directly to tyrosine-phosphorylated Gab1 isolated from activated RAMOS cells. In contrast, the Grb2 SH2 domain did not bind directly to Gab1 but instead to the Shc and SHP-2 associated with Gab1. We also show that Gab1 is present in the membrane-enriched particulate fraction of RAMOS cells and that Gab1/signaling protein complexes are found in this fraction after BCR engagement. Thus, tyrosine-phosphorylated Gab1 may recruit cytosolic signaling proteins to cellular membranes where they can act on membrane-bound targets. This may be a critical step in the activation of multiple BCR signaling pathways.

Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

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

Tong, Yuxin; Li, Yan; Gu, Hui

ArgBP2 is an adapter protein that plays an important role in actin-dependent processes such as cell adhesion and migration. However, its function and regulation mechanisms in gastric cancer have not yet been investigated. Here, we showed the low expression of ArgBP2 mRNA level in gastric tumor samples and its repressive function in the proliferation, migration, and invasion of gastric cancer cells. Then, we cloned and identified ArgBP2 promoter and verified that MORC2 bound to the promoter. Moreover, we demonstrated that MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of ArgBP2. Ourmore » results might thus contribute to understanding the molecular mechanisms of ArgBP2 regulation and suggesting ArgBP2 as a potential therapeutic target for gastric cancer. - Highlights: • ArgBP2 inhibits proliferation, migration, and invasion of gastric cancer cells. • Identification of ArgBP2 promoter and its transcription factor MORC2. • EZH2 is required in MORC2 down-regulating ArgBP2 via histone methylation.« less

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

PubMed Central

Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong

2017-01-01

The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system. PMID:28680299

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation.

PubMed

Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong; Park, Hwan Tae

2017-06-01

The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.

PubMed

Roskoski, Robert

2005-11-11

Signaling by stem cell factor and Kit, its receptor, plays important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic stem cells express Kit transcripts. Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a receptor protein-tyrosine kinase. The complete absence of stem cell factor or Kit is lethal. Deficiencies of either produce defects in red and white blood cell production, hypopigmentation, and sterility. Gain-of-function mutations of Kit are associated with several human neoplasms including acute myelogenous leukemia, gastrointestinal stromal tumors, and mastocytomas. Kit consists of an extracellular domain, a transmembrane segment, a juxtamembrane segment, and a protein kinase domain that contains an insert of about 80 amino acid residues. Binding of stem cell factor to Kit results in receptor dimerization and activation of protein kinase activity. The activated receptor becomes autophosphorylated at tyrosine residues that serve as docking sites for signal transduction molecules containing SH2 domains. The adaptor protein APS, Src family kinases, and Shp2 tyrosyl phosphatase bind to phosphotyrosine 568. Shp1 tyrosyl phosphatase and the adaptor protein Shc bind to phosphotyrosine 570. C-terminal Src kinase homologous kinase and the adaptor Shc bind to both phosphotyrosines 568 and 570. These residues occur in the juxtamembrane segment of Kit. Three residues in the kinase insert domain are phosphorylated and attract the adaptor protein Grb2 (Tyr703), phosphatidylinositol 3-kinase (Tyr721), and phospholipase Cgamma (Tyr730). Phosphotyrosine 900 in the distal kinase domain binds phosphatidylinositol 3-kinase which in turn binds the adaptor protein Crk. Phosphotyrosine 936, also in the distal kinase domain, binds the adaptor proteins APS, Grb2, and Grb7. Kit has the potential to participate in multiple signal transduction pathways as a result of

The Supercritical Pile Gamma-Ray Burst Model: The GRB Afterglow Steep Decline and Plateau Phase

NASA Technical Reports Server (NTRS)

Sultana, Joseph; Kazanas, D.; Mastichiadis, A.

2013-01-01

We present a process that accounts for the steep decline and plateau phase of the Swift X-Ray Telescope (XRT) light curves, vexing features of gamma-ray burst (GRB) phenomenology. This process is an integral part of the "supercritical pile" GRB model, proposed a few years ago to account for the conversion of the GRB kinetic energy into radiation with a spectral peak at E(sub pk) is approx. m(sub e)C(exp 2). We compute the evolution of the relativistic blast wave (RBW) Lorentz factor Gamma to show that the radiation-reaction force due to the GRB emission can produce an abrupt, small (approx. 25%) decrease in Gamma at a radius that is smaller (depending on conditions) than the deceleration radius R(sub D). Because of this reduction, the kinematic criticality criterion of the "supercritical pile" is no longer fulfilled. Transfer of the proton energy into electrons ceases and the GRB enters abruptly the afterglow phase at a luminosity smaller by approx. m(sub p)/m(sub e) than that of the prompt emission. If the radius at which this slow-down occurs is significantly smaller than R(sub D), the RBW internal energy continues to drive the RBW expansion at a constant (new) Gamma and its X-ray luminosity remains constant until R(sub D) is reached, at which point it resumes its more conventional decay, thereby completing the "unexpected" XRT light curve phase. If this transition occurs at R is approx. equal to R(sub D), the steep decline is followed by a flux decrease instead of a "plateau," consistent with the conventional afterglow declines. Besides providing an account of these peculiarities, the model suggests that the afterglow phase may in fact begin before the RBW reaches R is approx. equal to R(sub D), thus providing novel insights into GRB phenomenology.

The supercritical pile gamma-ray burst model: The GRB afterglow steep decline and plateau phase

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

Sultana, J.; Kazanas, D.; Mastichiadis, A., E-mail: joseph.sultana@um.edu.mt

2013-12-10

We present a process that accounts for the steep decline and plateau phase of the Swift X-Ray Telescope (XRT) light curves, vexing features of gamma-ray burst (GRB) phenomenology. This process is an integral part of the 'supercritical pile' GRB model, proposed a few years ago to account for the conversion of the GRB kinetic energy into radiation with a spectral peak at E {sub pk} ∼ m{sub e}c {sup 2}. We compute the evolution of the relativistic blast wave (RBW) Lorentz factor Γ to show that the radiation-reaction force due to the GRB emission can produce an abrupt, small (∼25%)more » decrease in Γ at a radius that is smaller (depending on conditions) than the deceleration radius R{sub D} . Because of this reduction, the kinematic criticality criterion of the 'supercritical pile' is no longer fulfilled. Transfer of the proton energy into electrons ceases and the GRB enters abruptly the afterglow phase at a luminosity smaller by ∼m{sub p} /m{sub e} than that of the prompt emission. If the radius at which this slow-down occurs is significantly smaller than R{sub D} , the RBW internal energy continues to drive the RBW expansion at a constant (new) Γ and its X-ray luminosity remains constant until R{sub D} is reached, at which point it resumes its more conventional decay, thereby completing the 'unexpected' XRT light curve phase. If this transition occurs at R ≅ R{sub D} , the steep decline is followed by a flux decrease instead of a 'plateau,' consistent with the conventional afterglow declines. Besides providing an account of these peculiarities, the model suggests that the afterglow phase may in fact begin before the RBW reaches R ≅ R{sub D} , thus providing novel insights into GRB phenomenology.« less

A MISSING-LINK IN THE SUPERNOVA–GRB CONNECTION: THE CASE OF SN 2012ap

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

Chakraborti, Sayan; Soderberg, Alicia; Kamble, Atish

2015-06-01

Gamma-ray bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly, usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However, supernovae with heavy ejecta can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for a few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. However, the ejecta from SN 2009bb was baryon loaded and in nearly free expansion formore » a year, unlike GRBs. We report the first supernova discovered without a GRB but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than one-sixth of the fluence from GRB 980425. This shows for the first time that central engines in SNe Ic, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.« less

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

NASA Astrophysics Data System (ADS)

Abbott, B. P.; Abbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Afrough, M.; Agarwal, B.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Allen, B.; Allen, G.; Allocca, A.; Aloy, M. A.; Altin, P. A.; Amato, A.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Angelova, S. V.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ascenzi, S.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Atallah, D. V.; Aufmuth, P.; Aulbert, C.; AultONeal, K.; Austin, C.; Avila-Alvarez, A.; Babak, S.; Bacon, P.; Bader, M. K. M.; Bae, S.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Banagiri, S.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barkett, K.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Bawaj, M.; Bayley, J. C.; Bazzan, M.; Bécsy, B.; Beer, C.; Bejger, M.; Belahcene, I.; Bell, A. S.; Berger, B. K.; Bergmann, G.; Bero, J. J.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Billman, C. R.; Birch, J.; Birney, R.; Birnholtz, O.; Biscans, S.; Biscoveanu, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blackman, J.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bloemen, S.; Bock, O.; Bode, N.; Boer, M.; Bogaert, G.; Bohe, A.; Bondu, F.; Bonilla, E.; Bonnand, R.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, S.; Bossie, K.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Broida, J. E.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brunett, S.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cabero, M.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderón Bustillo, J.; Callister, T. A.; Calloni, E.; Camp, J. B.; Canepa, M.; Canizares, P.; Cannon, K. C.; Cao, H.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Carney, M. F.; Casanueva Diaz, J.; Casentini, C.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Cerdá-Durán, P.; Cerretani, G.; Cesarini, E.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chase, E.; Chassande-Mottin, E.; Chatterjee, D.; Chatziioannou, K.; Cheeseboro, B. D.; Chen, H. Y.; Chen, X.; Chen, Y.; Cheng, H.-P.; Chia, H.; Chincarini, A.; Chiummo, A.; Chmiel, T.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, A. J. K.; Chua, S.; Chung, A. K. W.; Chung, S.; Ciani, G.; Ciolfi, R.; Cirelli, C. E.; Cirone, A.; Clara, F.; Clark, J. A.; Clearwater, P.; Cleva, F.; Cocchieri, C.; Coccia, E.; Cohadon, P.-F.; Cohen, D.; Colla, A.; Collette, C. G.; Cominsky, L. R.; Constancio, M., Jr.; Conti, L.; Cooper, S. J.; Corban, P.; Corbitt, T. R.; Cordero-Carrión, I.; Corley, K. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J.-P.; Countryman, S. T.; Couvares, P.; Covas, P. B.; Cowan, E. E.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cullen, T. J.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dal Canton, T.; Dálya, G.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dasgupta, A.; Da Silva Costa, C. F.; Dattilo, V.; Dave, I.; Davier, M.; Davis, D.; Daw, E. J.; Day, B.; De, S.; DeBra, D.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Pozzo, W.; Demos, N.; Denker, T.; Dent, T.; De Pietri, R.; Dergachev, V.; De Rosa, R.; DeRosa, R. T.; De Rossi, C.; DeSalvo, R.; de Varona, O.; Devenson, J.; Dhurandhar, S.; Díaz, M. C.; Di Fiore, L.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Doctor, Z.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Douglas, R.; Dovale Álvarez, M.; Downes, T. P.; Drago, M.; Dreissigacker, C.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dupej, P.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Eisenstein, R. A.; Essick, R. C.; Estevez, D.; Etienne, Z. B.; Etzel, T.; Evans, M.; Evans, T. M.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Farinon, S.; Farr, B.; Farr, W. M.; Fauchon-Jones, E. J.; Favata, M.; Fays, M.; Fee, C.; Fehrmann, H.; Feicht, J.; Fejer, M. M.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Finstad, D.; Fiori, I.; Fiorucci, D.; Fishbach, M.; Fisher, R. P.; Fitz-Axen, M.; Flaminio, R.; Fletcher, M.; Fong, H.; Font, J. A.; Forsyth, P. W. F.; Forsyth, S. S.; Fournier, J.-D.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Frey, V.; Fries, E. M.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H.; Gadre, B. U.; Gaebel, S. M.; Gair, J. R.; Gammaitoni, L.; Ganija, M. R.; Gaonkar, S. G.; Garcia-Quiros, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gaur, G.; Gayathri, V.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; George, D.; George, J.; Gergely, L.; Germain, V.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glover, L.; Goetz, E.; Goetz, R.; Gomes, S.; Goncharov, B.; González, G.; Gonzalez Castro, J. M.; Gopakumar, A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Grado, A.; Graef, C.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Gretarsson, E. M.; Groot, P.; Grote, H.; Grunewald, S.; Gruning, P.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Halim, O.; Hall, B. R.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O. A.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Haster, C.-J.; Haughian, K.; Healy, J.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hinderer, T.; Hoak, D.; Hofman, D.; Holt, K.; Holz, D. E.; Hopkins, P.; Horst, C.; Hough, J.; Houston, E. A.; Howell, E. J.; Hreibi, A.; Hu, Y. M.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Indik, N.; Inta, R.; Intini, G.; Isa, H. N.; Isac, J.-M.; Isi, M.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jiménez-Forteza, F.; Johnson, W. W.; Johnson-McDaniel, N. K.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kapadia, S. J.; Karki, S.; Karvinen, K. S.; Kasprzack, M.; Kastaun, W.; Katolik, M.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kawabe, K.; Kéfélian, F.; Keitel, D.; Kemball, A. J.; Kennedy, R.; Kent, C.; Key, J. S.; Khalili, F. Y.; Khan, I.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, Chunglee; Kim, J. C.; Kim, K.; Kim, W.; Kim, W. S.; Kim, Y.-M.; Kimbrell, S. J.; King, E. J.; King, P. J.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knowles, T. D.; Koch, P.; Koehlenbeck, S. M.; Koley, S.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kowalska, I.; Kozak, D. B.; Krämer, C.; Kringel, V.; Krishnan, B.; Królak, A.; Kuehn, G.; Kumar, P.; Kumar, R.; Kumar, S.; Kuo, L.; Kutynia, A.; Kwang, S.; Lackey, B. D.; Lai, K. H.; Landry, M.; Lang, R. N.; Lange, J.; Lantz, B.; Lanza, R. K.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, H. W.; Lee, K.; Lehmann, J.; Lenon, A.; Leonardi, M.; Leroy, N.; Letendre, N.; Levin, Y.; Li, T. G. F.; Linker, S. D.; Littenberg, T. B.; Liu, J.; Lo, R. K. L.; Lockerbie, N. A.; London, L. T.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lück, H.; Lumaca, D.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macas, R.; Macfoy, S.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña Hernandez, I.; Magaña-Sandoval, F.; Magaña Zertuche, L.; Magee, R. M.; Majorana, E.; Maksimovic, I.; Man, N.; Mandic, V.; Mangano, V.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Martelli, F.; Martellini, L.; Martin, I. W.; Martin, R. M.; Martynov, D. V.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McCuller, L.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McNeill, L.; McRae, T.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Mehmet, M.; Meidam, J.; Mejuto-Villa, E.; Melatos, A.; Mendell, G.; Mercer, R. A.; Merilh, E. L.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Metzdorff, R.; Meyers, P. M.; Miao, H.; Michel, C.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, A. L.; Miller, B. B.; Miller, J.; Millhouse, M.; Milovich-Goff, M. C.; Minazzoli, O.; Minenkov, Y.; Ming, J.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moffa, D.; Moggi, A.; Mogushi, K.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, C. J.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mours, B.; Mow-Lowry, C. M.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mukund, N.; Mullavey, A.; Munch, J.; Muñiz, E. A.; Muratore, M.; Murray, P. G.; Napier, K.; Nardecchia, I.; Naticchioni, L.; Nayak, R. K.; Neilson, J.; Nelemans, G.; Nelson, T. J. N.; Nery, M.; Neunzert, A.; Nevin, L.; Newport, J. M.; Newton, G.; Ng, K. K. Y.; Nguyen, T. T.; Nichols, D.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Noack, A.; Nocera, F.; Nolting, D.; North, C.; Nuttall, L. K.; Oberling, J.; O'Dea, G. D.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Okada, M. A.; Oliver, M.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; Ormiston, R.; Ortega, L. F.; O'Shaughnessy, R.; Ossokine, S.; Ottaway, D. J.; Overmier, H.; Owen, B. J.; Pace, A. E.; Page, J.; Page, M. A.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, Howard; Pan, Huang-Wei; Pang, B.; Pang, P. T. H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Parida, A.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patil, M.; Patricelli, B.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Penn, S.; Perez, C. J.; Perreca, A.; Perri, L. M.; Pfeiffer, H. P.; Phelps, M.; Piccinni, O. J.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pirello, M.; Pitkin, M.; Poe, M.; Poggiani, R.; Popolizio, P.; Porter, E. K.; Post, A.; Powell, J.; Prasad, J.; Pratt, J. W. W.; Pratten, G.; Predoi, V.; Prestegard, T.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L. G.; Puncken, O.; Punturo, M.; Puppo, P.; Pürrer, M.; Qi, H.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajan, C.; Rajbhandari, B.; Rakhmanov, M.; Ramirez, K. E.; Ramos-Buades, A.; Rapagnani, P.; Raymond, V.; Razzano, M.; Read, J.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Ren, W.; Reyes, S. D.; Ricci, F.; Ricker, P. M.; Rieger, S.; Riles, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, R.; Romel, C. L.; Romie, J. H.; Rosińska, D.; Ross, M. P.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Rutins, G.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Sakellariadou, M.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sampson, L. M.; Sanchez, E. J.; Sanchez, L. E.; Sanchis-Gual, N.; Sandberg, V.; Sanders, J. R.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Scheel, M.; Scheuer, J.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schönbeck, A.; Schreiber, E.; Schuette, D.; Schulte, B. W.; Schutz, B. F.; Schwalbe, S. G.; Scott, J.; Scott, S. M.; Seidel, E.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sequino, V.; Sergeev, A.; Shaddock, D. A.; Shaffer, T. J.; Shah, A. A.; Shahriar, M. S.; Shaner, M. B.; Shao, L.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sieniawska, M.; Sigg, D.; Silva, A. D.; Singer, L. P.; Singh, A.; Singhal, A.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, B.; Smith, J. R.; Smith, R. J. E.; Somala, S.; Son, E. J.; Sonnenberg, J. A.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Spencer, A. P.; Srivastava, A. K.; Staats, K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stevenson, S. P.; Stone, R.; Stops, D. J.; Strain, K. A.; Stratta, G.; Strigin, S. E.; Strunk, A.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sun, L.; Sunil, S.; Suresh, J.; Sutton, P. J.; Swinkels, B. L.; Szczepańczyk, M. J.; Tacca, M.; Tait, S. C.; Talbot, C.; Talukder, D.; Tanner, D. B.; Tápai, M.; Taracchini, A.; Tasson, J. D.; Taylor, J. A.; Taylor, R.; Tewari, S. V.; Theeg, T.; Thies, F.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Toland, K.; Tonelli, M.; Tornasi, Z.; Torres-Forné, A.; Torrie, C. I.; Töyrä, D.; Travasso, F.; Traylor, G.; Trinastic, J.; Tringali, M. C.; Trozzo, L.; Tsang, K. W.; Tse, M.; Tso, R.; Tsukada, L.; Tsuna, D.; Tuyenbayev, D.; Ueno, K.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; van Veggel, A. A.; Vardaro, M.; Varma, V.; Vass, S.; Vasúth, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Venugopalan, G.; Verkindt, D.; Vetrano, F.; Viceré, A.; Viets, A. D.; Vinciguerra, S.; Vine, D. J.; Vinet, J.-Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Walet, R.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, J. Z.; Wang, W. H.; Wang, Y. F.; Ward, R. L.; Warner, J.; Was, M.; Watchi, J.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Wessel, E. K.; Weßels, P.; Westerweck, J.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; Whiting, B. F.; Whittle, C.; Wilken, D.; Williams, D.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Woehler, J.; Wofford, J.; Wong, K. W. K.; Worden, J.; Wright, J. L.; Wu, D. S.; Wysocki, D. M.; Xiao, S.; Yamamoto, H.; Yancey, C. C.; Yang, L.; Yap, M. J.; Yazback, M.; Yu, Hang; Yu, Haocun; Yvert, M.; Zadrożny, A.; Zanolin, M.; Zelenova, T.; Zendri, J.-P.; Zevin, M.; Zhang, L.; Zhang, M.; Zhang, T.; Zhang, Y.-H.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, S. J.; Zhu, X. J.; Zimmerman, A. B.; Zucker, M. E.; Zweizig, J.; (LIGO Scientific Collaboration; Virgo Collaboration; Burns, E.; Veres, P.; Kocevski, D.; Racusin, J.; Goldstein, A.; Connaughton, V.; Briggs, M. S.; Blackburn, L.; Hamburg, R.; Hui, C. M.; von Kienlin, A.; McEnery, J.; Preece, R. D.; Wilson-Hodge, C. A.; Bissaldi, E.; Cleveland, W. H.; Gibby, M. H.; Giles, M. M.; Kippen, R. M.; McBreen, S.; Meegan, C. A.; Paciesas, W. S.; Poolakkil, S.; Roberts, O. J.; Stanbro, M.; Gamma-ray Burst Monitor, (Fermi; Savchenko, V.; Ferrigno, C.; Kuulkers, E.; Bazzano, A.; Bozzo, E.; Brandt, S.; Chenevez, J.; Courvoisier, T. J.-L.; Diehl, R.; Domingo, A.; Hanlon, L.; Jourdain, E.; Laurent, P.; Lebrun, F.; Lutovinov, A.; Mereghetti, S.; Natalucci, L.; Rodi, J.; Roques, J.-P.; Sunyaev, R.; Ubertini, P.; (INTEGRAL

2017-10-01

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is 5.0× {10}-8. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of (+1.74+/- 0.05) {{s}} between GRB 170817A and GW170817 to: (I) constrain the difference between the speed of gravity and the speed of light to be between -3× {10}-15 and +7× {10}-16 times the speed of light, (II) place new bounds on the violation of Lorentz invariance, (III) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1-1.4 per year during the 2018-2019 observing run and 0.3-1.7 per year at design sensitivity.

Observações das explosões cósmicas de raios gama GRB021004 e GRB021211 com o satélite HETE

NASA Astrophysics Data System (ADS)

Braga, J.; Ricker, G.; Hurley, K.; Lamb, D.; Grew, G.; et al.

2003-08-01

O High Energy Transient Explorer (HETE) é o primeiro satélite inteiramente dedicado ao estudo das explosões cósmicas de raios gama (ECRGs). Lançado em 9 de outubro de 2000, o HETE possui instrumentação capaz de observar as ECRGs desde o UV até raios gama e localizá-las com precisão de ~ 1-10 minutos de arco. As localizações das ECRGs detectadas são disseminadas rapidamente (em alguns segundos) pela Internet através de uma rede de estações de recepção ao longo do equador. A participação brasileira nesse projeto se dá através da montagem e operação de uma estação de recepção em Natal, RN, e da participação na equipe científica da missão. Neste trabalho são apresentados resultados da observação pelo HETE de duas ECRGs: GRB 021004 e GRB 021211. A GRB021004 foi detectada em raios gama pelo HETE em 4 de outubro de 2002 e localizada em raios-X em apenas 48 s, quando a emissão de raios gama ainda estava se processando. A explosão, relativamente brilhante e longa, durou aproximadamente 100 s. Um transiente óptico de magnitude 15 foi detectado no local da explosão nove minutos após o evento, e observações realizadas após 7 horas determinaram um desvio para o vermelho de absorção de 1,6. O GRB021004 foi o burst mais bem observado até o momento e suas observações em vários comprimentos de onda têm sido fundamentais para o aprimoramento dos modelos de ECRGs. O GRB21211, um burst brilhante e rico em raios-X, foi detectado em 11 de dezembro de 2002 e localizado em raios-X em 22 s após o início do evento. A duração do burst foi de 2,3 s em altas energias (85 a 400 keV) e de 8,5 s em baixas energias (2 a 10 keV). Caso essa explosão não tivesse sido rapidamente localizada pelo HETE, ela teria sido classificada como "opticamente escura", já que o transiente óptico decaiu rapidamente de R < 14 a R»19 dentro dos primeiros 20 minutos e já estava mais fraco do que R»23 depois de 24 horas da ocorrência do burst. Ser

Search for TeV Gamma-ray Emission from GRB 100621A, an extremely bright GRB in X-rays, with H.E.S.S.

NASA Astrophysics Data System (ADS)

H.E.S.S. Collaboration; Abramowski, A.; Aharonian, F.; Ait Benkhali, F.; Akhperjanian, A. G.; Angüner, E.; Anton, G.; Balenderan, S.; Balzer, A.; Barnacka, A.; Becherini, Y.; Becker Tjus, J.; Bernlöhr, K.; Birsin, E.; Bissaldi, E.; Biteau, J.; Böttcher, M.; Boisson, C.; Bolmont, J.; Bordas, P.; Brucker, J.; Brun, F.; Brun, P.; Bulik, T.; Carrigan, S.; Casanova, S.; Cerruti, M.; Chadwick, P. M.; Chalme-Calvet, R.; Chaves, R. C. G.; Cheesebrough, A.; Chrétien, M.; Colafrancesco, S.; Cologna, G.; Conrad, J.; Couturier, C.; Dalton, M.; Daniel, M. K.; Davids, I. D.; Degrange, B.; Deil, C.; deWilt, P.; Dickinson, H. J.; Djannati-Ataï, A.; Domainko, W.; O'C. Drury, L.; Dubus, G.; Dutson, K.; Dyks, J.; Dyrda, M.; Edwards, T.; Egberts, K.; Eger, P.; Espigat, P.; Farnier, C.; Fegan, S.; Feinstein, F.; Fernandes, M. V.; Fernandez, D.; Fiasson, A.; Fontaine, G.; Förster, A.; Füßling, M.; Gajdus, M.; Gallant, Y. A.; Garrigoux, T.; Giebels, B.; Glicenstein, J. F.; Grondin, M.-H.; Grudzińska, M.; Häffner, S.; Hahn, J.; Harris, J.; Heinzelmann, G.; Henri, G.; Hermann, G.; Hervet, O.; Hillert, A.; Hinton, J. A.; Hofmann, W.; Hofverberg, P.; Holler, M.; Horns, D.; Jacholkowska, A.; Jahn, C.; Jamrozy, M.; Janiak, M.; Jankowsky, F.; Jung, I.; Kastendieck, M. A.; Katarzyński, K.; Katz, U.; Kaufmann, S.; Khélifi, B.; Kieffer, M.; Klepser, S.; Klochkov, D.; Kluźniak, W.; Kneiske, T.; Kolitzus, D.; Komin, Nu.; Kosack, K.; Krakau, S.; Krayzel, F.; Krüger, P. P.; Laffon, H.; Lamanna, G.; Lefaucheur, J.; Lemière, A.; Lemoine-Goumard, M.; Lenain, J.-P.; Lennarz, D.; Lohse, T.; Lopatin, A.; Lu, C.-C.; Marandon, V.; Marcowith, A.; Marx, R.; Maurin, G.; Maxted, N.; Mayer, M.; McComb, T. J. L.; Méhault, J.; Menzler, U.; Meyer, M.; Moderski, R.; Mohamed, M.; Moulin, E.; Murach, T.; Naumann, C. L.; de Naurois, M.; Niemiec, J.; Nolan, S. J.; Oakes, L.; O'Brien, P. T.; Ohm, S.; de Oña Wilhelmi, E.; Opitz, B.; Ostrowski, M.; Oya, I.; Panter, M.; Parsons, R. D.; Paz Arribas, M.; Pekeur, N. W.; Pelletier, G.; Perez, J.; Petrucci, P.-O.; Peyaud, B.; Pita, S.; Poon, H.; Pühlhofer, G.; Punch, M.; Quirrenbach, A.; Raab, S.; Raue, M.; Reimer, A.; Reimer, O.; Renaud, M.; de los Reyes, R.; Rieger, F.; Rob, L.; Romoli, C.; Rosier-Lees, S.; Rowell, G.; Rudak, B.; Rulten, C. B.; Sahakian, V.; Sanchez, D. A.; Santangelo, A.; Schlickeiser, R.; Schüssler, F.; Schulz, A.; Schwanke, U.; Schwarzburg, S.; Schwemmer, S.; Sol, H.; Spengler, G.; Spies, F.; Stawarz, Ł.; Steenkamp, R.; Stegmann, C.; Stinzing, F.; Stycz, K.; Sushch, I.; Szostek, A.; Tam, P. H. T.; Tavernet, J.-P.; Tavernier, T.; Taylor, A. M.; Terrier, R.; Tluczykont, M.; Trichard, C.; Valerius, K.; van Eldik, C.; Vasileiadis, G.; Venter, C.; Viana, A.; Vincent, P.; Völk, H. J.; Volpe, F.; Vorster, M.; Wagner, S. J.; Wagner, P.; Ward, M.; Weidinger, M.; Weitzel, Q.; White, R.; Wierzcholska, A.; Willmann, P.; Wörnlein, A.; Wouters, D.; Zacharias, M.; Zajczyk, A.; Zdziarski, A. A.; Zech, A.; Zechlin, H.-S.

2014-05-01

The long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0.3-10 keV range, has been observed with the H.E.S.S. imaging air Cherenkov telescope array, sensitive to gamma radiation in the very-high-energy (VHE, >100 GeV) regime. Due to its relatively small redshift of z ~ 0.5, the favourable position in the southern sky and the relatively short follow-up time (<700 s after the satellite trigger) of the H.E.S.S. observations, this GRB could be within the sensitivity reach of the H.E.S.S. instrument. The analysis of the H.E.S.S. data shows no indication of emission and yields an integral flux upper limit above ~380 GeV of 4.2 × 10-12 cm-2 s-1 (95% confidence level), assuming a simple Band function extension model. A comparison to a spectral-temporal model, normalised to the prompt flux at sub-MeV energies, constraints the existence of a temporally extended and strong additional hard power law, as has been observed in the other bright X-ray GRB 130427A. A comparison between the H.E.S.S. upper limit and the contemporaneous energy output in X-rays constrains the ratio between the X-ray and VHE gamma-ray fluxes to be greater than 0.4. This value is an important quantity for modelling the afterglow and can constrain leptonic emission scenarios, where leptons are responsible for the X-ray emission and might produce VHE gamma rays.

Viruses are a dominant driver of protein adaptation in mammals.

PubMed

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-05-17

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.

Relationship Between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple Negative Breast Cancer

PubMed Central

Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Kenny, Paraic A.; Sledge, George W.; Gray, Robert

2012-01-01

Purpose To perform an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental design RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative RT-PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results GRB7 was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn’s adjusted p value=0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR 2.31, p=0.04 using the median as the split). The 5-year recurrence rates were 10.5% (95% confidence intervals [CI] 7.8%, 14.1%) in the low and 20.4% (95% CI 16.5%, 25.0%) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. PMID:21933890

The Observable Signatures of GRB Cocoons

NASA Astrophysics Data System (ADS)

Nakar, Ehud; Piran, Tsvi

2017-01-01

As a long gamma-ray burst (GRB) jet propagates within the stellar atmosphere it creates a cocoon composed of an outer Newtonian shocked stellar material and an inner (possibly relativistic) shocked jet. The jet deposits {10}51{--}{10}52 erg into this cocoon. This is comparable to the energies of the GRB and of the accompanying supernova, yet the cocoon’s signature has been largely ignored. The cocoon radiates a fraction of this energy as it expands, following the breakout from the star, and later as it interacts with the surrounding matter. We explore the possible signatures of this emission and outline a framework to calculate them from the conditions of the cocoon at the time of the jet breakout. The cocoon signature depends strongly on the, currently unknown, mixing between the shocked jet and shocked stellar material. With no mixing the γ-ray emission from the cocoon is so bright that it should have been already detected. The lack of such detections indicates that some mixing must take place. For partial and full mixing the expected signals are weaker than regular GRB afterglows. However, the latter are highly beamed while the former are wider. Future optical, UV, and X-ray transient searches, like LSST, ZTF, ULTRASAT, ISS-Lobster, and others, will most likely detect such signals, providing a wealth of information on the progenitors and jets of GRBs. While we focus on long GRBs, analogous (but weaker) cocoons may arise in short GRBs. Their signatures might be the most promising electromagnetic counterparts for gravitational wave signals from compact binary mergers.

The 2175 Å Extinction Feature in the Optical Afterglow Spectrum of GRB 180325A at z = 2.25

NASA Astrophysics Data System (ADS)

Zafar, T.; Heintz, K. E.; Fynbo, J. P. U.; Malesani, D.; Bolmer, J.; Ledoux, C.; Arabsalmani, M.; Kaper, L.; Campana, S.; Starling, R. L. C.; Selsing, J.; Kann, D. A.; de Ugarte Postigo, A.; Schweyer, T.; Christensen, L.; Møller, P.; Japelj, J.; Perley, D.; Tanvir, N. R.; D’Avanzo, P.; Hartmann, D. H.; Hjorth, J.; Covino, S.; Sbarufatti, B.; Jakobsson, P.; Izzo, L.; Salvaterra, R.; D’Elia, V.; Xu, D.

2018-06-01

The ultraviolet (UV) extinction feature at 2175 Å is ubiquitously observed in the Galaxy but is rarely detected at high redshifts. Here we report the spectroscopic detection of the 2175 Å bump on the sightline to the γ-ray burst (GRB) afterglow GRB 180325A at z = 2.2486, the only unambiguous detection over the past 10 years of GRB follow-up, at four different epochs with the Nordic Optical Telescope (NOT) and the Very Large Telescope (VLT)/X-shooter. Additional photometric observations of the afterglow are obtained with the Gamma-Ray burst Optical and Near-Infrared Detector (GROND). We construct the near-infrared to X-ray spectral energy distributions (SEDs) at four spectroscopic epochs. The SEDs are well described by a single power law and an extinction law with R V ≈ 4.4, A V ≈ 1.5, and the 2175 Å extinction feature. The bump strength and extinction curve are shallower than the average Galactic extinction curve. We determine a metallicity of [Zn/H] > ‑0.98 from the VLT/X-shooter spectrum. We detect strong neutral carbon associated with the GRB with equivalent width of W r(λ 1656) = 0.85 ± 0.05. We also detect optical emission lines from the host galaxy. Based on the Hα emission-line flux, the derived dust-corrected star formation rate is ∼46 ± 4 M ⊙ yr‑1 and the predicted stellar mass is log M */M ⊙ ∼ 9.3 ± 0.4, suggesting that the host galaxy is among the main-sequence star-forming galaxies. Based on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO program 0100.D‑0649(A).

Could GRB170817A be really correlated to an NS-NS merging?

NASA Astrophysics Data System (ADS)

Fargion, D.; Khlopov, M. Yu.; Oliva, P.

The exciting development of gravitational wave (GW) astronomy in the correlation of LIGO and VIRGO detection of GW signals makes possible to expect registration of effects of not only binary black hole (BH) coalescence but also binary neutron star (NS) merging accompanied by electromagnetic (gamma ray burst; GRB) signal. Here we consider the possibility that an NS, merging in an NS-NS or NS-BH system might be (soon) observed in correlation with any LIGO-VIRGO GWs detection. We analyze as an example the recent case of the short GRB170817A observed by Fermi and integral. The associated optical transient (OT) source in NGC4993 implies a rare near source, a consequent averaged large rate of such events (almost) compatible with expected NS-NS merging rate. However the expected beamed GRB (or short GRB) may be mostly aligned to a different direction than ours. Therefore, even soft GRB photons, spread more than hard ones, might be hardly able to shower to us. Nevertheless, a prompt spiraling electron turbine jet in largest magnetic fields, at the base of the NS-NS collapse, might shine by its tangential synchrotron radiation in spread way with its skimming photons shining in large open disk. The consequent solid angle for such soft disk gamma radiation may be large enough to be nevertheless often observed.

Water-refined solution structure of the human Grb7-SH2 domain in complex with the erbB2 receptor peptide pY1139.

PubMed

Pias, Sally C; Johnson, Dennis L; Smith, David E; Lyons, Barbara A

2012-08-01

We report a refinement in implicit water of the previously published solution structure of the Grb7-SH2 domain bound to the erbB2 receptor peptide pY1139. Structure quality measures indicate substantial improvement, with residues in the most favored regions of the Ramachandran plot increasing by 14 % and with WHAT IF statistics (Vriend, G. J. Mol. Graph., 1990, 8(1), 52-56) falling closer to expected values for well-refined structures.

Search for High-Energy Muon Neutrinos from the "Naked-Eye" GRB 080319B with the IceCube Neutrino Telescope

NASA Astrophysics Data System (ADS)

Abbasi, R.; Abdou, Y.; Abu-Zayyad, T.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Andeen, K.; Auffenberg, J.; Bai, X.; Baker, M.; Barwick, S. W.; Bay, R.; Bazo Alba, J. L.; Beattie, K.; Beatty, J. J.; Bechet, S.; Becker, J. K.; Becker, K.-H.; Benabderrahmane, M. L.; Berdermann, J.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Bissok, M.; Blaufuss, E.; Boersma, D. J.; Bohm, C.; Bolmont, J.; Botner, O.; Bradley, L.; Braun, J.; Breder, D.; Castermans, T.; Chirkin, D.; Christy, B.; Clem, J.; Cohen, S.; Cowen, D. F.; D'Agostino, M. V.; Danninger, M.; Day, C. T.; De Clercq, C.; Demirörs, L.; Depaepe, O.; Descamps, F.; Desiati, P.; de Vries-Uiterweerd, G.; DeYoung, T.; Diaz-Velez, J. C.; Dreyer, J.; Dumm, J. P.; Duvoort, M. R.; Edwards, W. R.; Ehrlich, R.; Eisch, J.; Ellsworth, R. W.; Engdegård, O.; Euler, S.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Feusels, T.; Filimonov, K.; Finley, C.; Foerster, M. M.; Fox, B. D.; Franckowiak, A.; Franke, R.; Gaisser, T. K.; Gallagher, J.; Ganugapati, R.; Gerhardt, L.; Gladstone, L.; Goldschmidt, A.; Goodman, J. A.; Gozzini, R.; Grant, D.; Griesel, T.; Groß, A.; Grullon, S.; Gunasingha, R. M.; Gurtner, M.; Ha, C.; Hallgren, A.; Halzen, F.; Han, K.; Hanson, K.; Hasegawa, Y.; Heise, J.; Helbing, K.; Herquet, P.; Hickford, S.; Hill, G. C.; Hoffman, K. D.; Hoshina, K.; Hubert, D.; Huelsnitz, W.; Hülß, J.-P.; Hulth, P. O.; Hultqvist, K.; Hussain, S.; Imlay, R. L.; Inaba, M.; Ishihara, A.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Joseph, J. M.; Kampert, K.-H.; Kappes, A.; Karg, T.; Karle, A.; Kelley, J. L.; Kenny, P.; Kiryluk, J.; Kislat, F.; Klein, S. R.; Knops, S.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Kowalski, M.; Kowarik, T.; Krasberg, M.; Kuehn, K.; Kuwabara, T.; Labare, M.; Lafebre, S.; Laihem, K.; Landsman, H.; Lauer, R.; Lennarz, D.; Lucke, A.; Lundberg, J.; Lünemann, J.; Madsen, J.; Majumdar, P.; Maruyama, R.; Mase, K.; Matis, H. S.; McParland, C. P.; Meagher, K.; Merck, M.; Mészáros, P.; Middell, E.; Milke, N.; Miyamoto, H.; Mohr, A.; Montaruli, T.; Morse, R.; Movit, S. M.; Münich, K.; Nahnhauer, R.; Nam, J. W.; Nießen, P.; Nygren, D. R.; Odrowski, S.; Olivas, A.; Olivo, M.; Ono, M.; Panknin, S.; Patton, S.; Pérez de los Heros, C.; Petrovic, J.; Piegsa, A.; Pieloth, D.; Pohl, A. C.; Porrata, R.; Potthoff, N.; Price, P. B.; Prikockis, M.; Przybylski, G. T.; Rawlins, K.; Redl, P.; Resconi, E.; Rhode, W.; Ribordy, M.; Rizzo, A.; Rodrigues, J. P.; Roth, P.; Rothmaier, F.; Rott, C.; Roucelle, C.; Rutledge, D.; Ryckbosch, D.; Sander, H.-G.; Sarkar, S.; Schlenstedt, S.; Schmidt, T.; Schneider, D.; Schukraft, A.; Schulz, O.; Schunck, M.; Seckel, D.; Semburg, B.; Seo, S. H.; Sestayo, Y.; Seunarine, S.; Silvestri, A.; Slipak, A.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stephens, G.; Stezelberger, T.; Stokstad, R. G.; Stoufer, M. C.; Stoyanov, S.; Strahler, E. A.; Straszheim, T.; Sulanke, K.-H.; Sullivan, G. W.; Swillens, Q.; Taboada, I.; Tamburro, A.; Tarasova, O.; Tepe, A.; Ter-Antonyan, S.; Terranova, C.; Tilav, S.; Toale, P. A.; Tosi, D.; Turčan, D.; van Eijndhoven, N.; Vandenbroucke, J.; Van Overloop, A.; Voigt, B.; Walck, C.; Waldenmaier, T.; Walter, M.; Wendt, C.; Westerhoff, S.; Whitehorn, N.; Wiebusch, C. H.; Wiedemann, A.; Wikström, G.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Xu, X. W.; Yodh, G.; Yoshida, S.; IceCube Collaboration

2009-08-01

We report on a search with the IceCube detector for high-energy muon neutrinos from GRB 080319B, one of the brightest gamma-ray bursts (GRBs) ever observed. The fireball model predicts that a mean of 0.1 events should be detected by IceCube for a bulk Lorentz boost of the jet of 300. In both the direct on-time window of 66 s and an extended window of about 300 s around the GRB, no excess was found above background. The 90% CL upper limit on the number of track-like events from the GRB is 2.7, corresponding to a muon neutrino fluence limit of 9.5 × 10-3 erg cm-2 in the energy range between 120 TeV and 2.2 PeV, which contains 90% of the expected events.

The Supercritical Pile GRB Model: The Prompt to Afterglow Evolution

NASA Technical Reports Server (NTRS)

Kazanas, Demosthenes

2008-01-01

The 'Supercritical Pile' is a very economical gamma ray burst (GRB) model that provides for the efficient conversion of the energy stored in the protons of a Relativistic Blast Wave (RBW) into radiation and at the same time produces - in the prompt GRB phase, even in the absence of any particle acceleration - a spectral peak at an energy sim 1 MeV. We extend this model to include also the evolution of the RBW Lorentz factor Gamma and thus follow the spectral and temporal features of this model into the early GRB afterglow stage. One of the novel features of the present treatment is the inclusion of the feedback of the GRB produced radiation on the evolution of Gamma with radius. This feedback and the presence of kinematic and dynamic thresholds in the model can be the sources of rich time evolution which we have begun to explore. In particular, one can this way obtain afterglow light curves with steep decays followed by the more conventional flatter afterglow slopes, while at the same time preserving the desirable features of the model, i.e. the well defined relativistic electron source and radiative processes that produce the proper peak in the nu F spectra. Furthermore, the existence of a kinematic threshold in this model provides for a operational distinction of the prompt and afterglow GRB stages; in fact, the afterglow stage sets in when the RBW Lorentz factor cannot anymore fulfill the kinematic condition for pair formation in the photon - proton pair production reactions that constitute the fundamental process for the dissipation of the blast wave kinetic energy. We present the results of a specific set of parameters of this model with emphasis on the multiwavelength prompt emission and transition to the early afterglow.

Glypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10

PubMed Central

Cheng, Wei; Huang, Po-Chun; Chao, Hsiao-Mei; Jeng, Yung-Ming; Hsu, Hey-Chi; Pan, Hung-Wei; Hwu, Wuh-Liang; Lee, Yu-May

2017-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels. GPC3 bound to Grb10, a mediator of ligand-induced receptor ubiquitination, and the overexpression of Grb10 blocked GPC3-enhanced IGF-1-induced ERK phosphorylation. GPC3 promoted the growth of NIH3T3 and PLC-PRF-5 cells in serum-free medium but did not promote the growth of IGF-1R negative R- cells. Grb10 overexpression decreased GPC3-promoted cell growth. Therefore, the present study elucidates the mechanisms of GPC3-induced oncogenicity, which may highlight new strategies for the treatment of HCC. PMID:29113314

Thermal Emissions Spanning the Prompt and the Afterglow Phases of the Ultra-long GRB 130925A

NASA Astrophysics Data System (ADS)

Basak, Rupal; Rao, A. R.

2015-07-01

GRB 130925A is an ultra-long gamma-ray burst (GRB), and it shows clear evidence for thermal emission in the soft X-ray data of the Swift/X-ray Telescope (XRT; ∼0.5 keV), lasting until the X-ray afterglow phase. Due to the long duration of the GRB, the burst could be studied in hard X-rays with high-resolution focusing detectors (NuSTAR). The blackbody temperature, as measured by the Swift/XRT, shows a decreasing trend until the late phase (Piro et al.) whereas the high-energy data reveal a significant blackbody component during the late epochs at an order of magnitude higher temperature (∼5 keV) compared to contemporaneous low energy data (Bellm et al.). We resolve this apparent contradiction by demonstrating that a model with two black bodies and a power law (2BBPL) is consistent with the data right from the late prompt emission to the afterglow phase. Both blackbodies show a similar cooling behavior up to late times. We invoke a structured jet, having a fast spine and a slower sheath layer, to identify the location of these blackbodies. Independent of the physical interpretation, we propose that the 2BBPL model is a generic feature of the prompt emission of all long GRBs, and the thermal emission found in the afterglow phase of different GRBs reflects the lingering thermal component of the prompt emission with different timescales. We strengthen this proposal by pointing out a close similarity between the spectral evolutions of this GRB and GRB 090618, a source with significant wide band data during the early afterglow phase.

The spatial architecture of protein function and adaptation

PubMed Central

McLaughlin, Richard N.; Poelwijk, Frank J.; Raman, Arjun; Gosal, Walraj S.; Ranganathan, Rama

2014-01-01

Statistical analysis of protein evolution suggests a design for natural proteins in which sparse networks of coevolving amino acids (termed sectors) comprise the essence of three-dimensional structure and function1, 2, 3, 4, 5. However, proteins are also subject to pressures deriving from the dynamics of the evolutionary process itself—the ability to tolerate mutation and to be adaptive to changing selection pressures6, 7, 8, 9, 10. To understand the relationship of the sector architecture to these properties, we developed a high-throughput quantitative method for a comprehensive single-mutation study in which every position is substituted individually to every other amino acid. Using a PDZ domain (PSD95pdz3) model system, we show that sector positions are functionally sensitive to mutation, whereas non-sector positions are more tolerant to substitution. In addition, we find that adaptation to a new binding specificity initiates exclusively through variation within sector residues. A combination of just two sector mutations located near and away from the ligand-binding site suffices to switch the binding specificity of PSD95pdz3 quantitatively towards a class-switching ligand. The localization of functional constraint and adaptive variation within the sector has important implications for understanding and engineering proteins. PMID:23041932

Chlorogenic acid inhibits hypoxia-induced pulmonary artery smooth muscle cells proliferation via c-Src and Shc/Grb2/ERK2 signaling pathway.

PubMed

Li, Qun-Yi; Zhu, Ying-Feng; Zhang, Meng; Chen, Li; Zhang, Zhen; Du, Yong-Li; Ren, Guo-Qiang; Tang, Jian-Min; Zhong, Ming-Kang; Shi, Xiao-Jin

2015-03-15

Chlorogenic acid (CGA), abundant in coffee and particular fruits, can modulate hypertension and vascular dysfunction. Hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation has been tightly linked to vascular remodeling in pulmonary arterial hypertension (PAH). Thus, the present study was designed to investigate the effect of CGA on hypoxia-induced proliferation in cultured rat PASMCs. The data showed that CGA potently inhibited PASMCs proliferation and DNA synthesis induced by hypoxia. These inhibitory effects were associated with G1 cell cycle arrest and down-regulation of cell cycle proteins. Treatment with CGA reduced hypoxia-induced hypoxia inducible factor 1α (HIF-1α) expression and trans-activation. Furthermore, hypoxia-evoked c-Src phosphorylation was inhibited by CGA. In vitro ELISA-based tyrosine kinase assay indicated that CGA was a direct inhibitor of c-Src. Moreover, CGA attenuated physical co-association of c-Src/Shc/Grb2 and ERK2 phosphorylation in PASMCs. These results suggest that CGA inhibits hypoxia-induced proliferation in PASMCs via regulating c-Src-mediated signaling pathway. In vivo investigation showed that chronic CGA treatment inhibits monocrotaline-induced PAH in rats. These findings presented here highlight the possible therapeutic use of CGA in hypoxia-related PAH. Copyright © 2015 Elsevier B.V. All rights reserved.

Viruses are a dominant driver of protein adaptation in mammals

PubMed Central

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-01-01

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001 PMID:27187613

The Supercritical Pile GRB Model: The Prompt to Afterglow Evolution

NASA Technical Reports Server (NTRS)

Mastichiadis, A.; Kazanas, D.

2009-01-01

The "Supercritical Pile" is a very economical GRB model that provides for the efficient conversion of the energy stored in the protons of a Relativistic Blast Wave (RBW) into radiation and at the same time produces - in the prompt GRB phase, even in the absence of any particle acceleration - a spectral peak at energy approx. 1 MeV. We extend this model to include the evolution of the RBW Lorentz factor Gamma and thus follow its spectral and temporal features into the early GRB afterglow stage. One of the novel features of the present treatment is the inclusion of the feedback of the GRB produced radiation on the evolution of Gamma with radius. This feedback and the presence of kinematic and dynamic thresholds in the model can be the sources of rich time evolution which we have began to explore. In particular. one can this may obtain afterglow light curves with steep decays followed by the more conventional flatter afterglow slopes, while at the same time preserving the desirable features of the model, i.e. the well defined relativistic electron source and radiative processes that produce the proper peak in the (nu)F(sub nu), spectra. In this note we present the results of a specific set of parameters of this model with emphasis on the multiwavelength prompt emission and transition to the early afterglow.

The association of GRB 060218 with a supernova and the evolution of the shock wave.

PubMed

Campana, S; Mangano, V; Blustin, A J; Brown, P; Burrows, D N; Chincarini, G; Cummings, J R; Cusumano, G; Della Valle, M; Malesani, D; Mészáros, P; Nousek, J A; Page, M; Sakamoto, T; Waxman, E; Zhang, B; Dai, Z G; Gehrels, N; Immler, S; Marshall, F E; Mason, K O; Moretti, A; O'Brien, P T; Osborne, J P; Page, K L; Romano, P; Roming, P W A; Tagliaferri, G; Cominsky, L R; Giommi, P; Godet, O; Kennea, J A; Krimm, H; Angelini, L; Barthelmy, S D; Boyd, P T; Palmer, D M; Wells, A A; White, N E

2006-08-31

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.

FERMI observations of high-energy gamma-ray emission from GRB 090217A

DOE PAGES

Ackermann, M.; Ajello, M.; Baldini, L.; ...

2010-06-22

The Fermi observatory is advancing our knowledge of gamma-ray bursts (GRBs) through pioneering observations at high energies, covering more than seven decades in energy with the two on-board detectors, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). Here, we report on the observation of the long GRB 090217A which triggered the GBM and has been detected by the LAT with a significance greater than 9σ. We present the GBM and LAT observations and on-ground analyses, including the time-resolved spectra and the study of the temporal profile from 8 keV up to ~1 GeV. All spectra are wellmore » reproduced by a Band model. We compare these observations to the first two LAT-detected, long bursts GRB 080825C and GRB 080916C. These bursts were found to have time-dependent spectra and exhibited a delayed onset of the high-energy emission, which are not observed in the case of GRB 090217A. We discuss some theoretical implications for the high-energy emission of GRBs.« less

F2Dock: Fast Fourier Protein-Protein Docking

PubMed Central

Bajaj, Chandrajit; Chowdhury, Rezaul; Siddavanahalli, Vinay

2009-01-01

The functions of proteins is often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination and understanding function and structure relationships. In this paper we extend our non-uniform fast Fourier transform docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic potential based scores only, F2Dock is structured to incorporate Lennard-Jones potential and re-ranking docking solutions based on desolvation energy. PMID:21071796

Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents.

PubMed

Saleem, A; Datta, R; Yuan, Z M; Kharbanda, S; Kufe, D

1995-12-01

The cellular response to 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of Jun/AP-1, induction of c-jun transcription, and programmed cell death. The stress-activated protein (SAP) kinases stimulate the transactivation function of c-jun by amino terminal phosphorylation. The present work demonstrates that ara-C activates p54 SAP kinase. The finding that SAP kinase is also activated by alkylating agents (mitomycin C and cisplatinum) and the topoisomerase I inhibitor 9-amino-camptothecin supports DNA damage as an initial signal in this cascade. The results demonstrate that ara-C also induces binding of SAP kinase to the SH2/SH3-containing adapter protein Grb2. SAP kinase binds to the SH3 domains of Grb2, while interaction of the p85 alpha-subunit of phosphatidylinositol 3-kinase complex. The results also demonstrate that ara-C treatment is associated with inhibition of lipid and serine kinase activities of PI 3-kinase. The potential significance of the ara-C-induced interaction between SAP kinase and PI 3-kinase is further supported by the demonstration that Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. The finding that Wortmannin treatment is also associated with internucleosomal DNA fragmentation may support a potential link between PI 3-kinase and regulation of both SAP kinase and programmed cell death.

Large-amplitude late-time radio variability in GRB 151027B

NASA Astrophysics Data System (ADS)

Greiner, J.; Bolmer, J.; Wieringa, M.; van der Horst, A. J.; Petry, D.; Schulze, S.; Knust, F.; de Bruyn, G.; Krühler, T.; Wiseman, P.; Klose, S.; Delvaux, C.; Graham, J. F.; Kann, D. A.; Moin, A.; Nicuesa-Guelbenzu, A.; Schady, P.; Schmidl, S.; Schweyer, T.; Tanga, M.; Tingay, S.; van Eerten, H.; Varela, K.

2018-06-01

Context. Deriving physical parameters from gamma-ray burst (GRB) afterglow observations remains a challenge, even 20 years after the discovery of afterglows. The main reason for the lack of progress is that the peak of the synchrotron emission is in the sub-mm range, thus requiring radio observations in conjunction with X-ray/optical/near-infrared data in order to measure the corresponding spectral slopes and consequently remove the ambiguity with respect to slow vs. fast cooling and the ordering of the characteristic frequencies. Aims: We have embarked on a multifrequency, multi-epoch observing campaign to obtain sufficient data for a given GRB that allows us to test the simplest version of the fireball afterglow model. Methods: We observed GRB 151027B, the 1000th Swift-detected GRB, with GROND in the optical-near-IR, ALMA in the sub-millimeter, ATCA in the radio band; we combined this with public Swift/XRT X-ray data. Results: While some observations at crucial times only return upper limits or surprising features, the fireball model is narrowly constrained by our data set, and allows us to draw a consistent picture with a fully determined parameter set. Surprisingly, we find rapid, large-amplitude flux density variations in the radio band which are extreme not only for GRBs, but generally for any radio source. We interpret them as scintillation effects, though their extreme nature requires the scattering screen to be at a much smaller distance than usually assumed, multiple screens, or a combination of the two. Conclusions: The data are consistent with the simplest fireball scenario for a blast wave moving into a constant-density medium, and slow-cooling electrons. All fireball parameters are constrained at or better than a factor of 2, except for the density and the fraction of the energy in the magnetic field which has a factor of 10 uncertainty in both directions. This paper makes use of the following data: ATCA: Proposal C2955 (PI: Greiner), ALMA: ADS

GRB 090227B: THE MISSING LINK BETWEEN THE GENUINE SHORT AND LONG GAMMA-RAY BURSTS

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

Muccino, M.; Ruffini, R.; Bianco, C. L.

2013-02-15

The time-resolved spectral analysis of GRB 090227B, made possible by the Fermi-GBM data, allows us to identify in this source the missing link between the genuine short and long gamma-ray bursts (GRBs). Within the Fireshell model of the GRBs we predict genuine short GRBs: bursts with the same inner engine of the long bursts but endowed with a severely low value of the baryon load, B {approx}< 5 Multiplication-Sign 10{sup -5}. A first energetically predominant emission occurs at the transparency of the e {sup +} e {sup -} plasma, the Proper-GRB (P-GRB), followed by a softer emission, the extended afterglow.more » The typical separation between the two emissions is expected to be of the order of 10{sup -3}-10{sup -2} s. We identify the P-GRB of GRB 090227B in the first 96 ms of emission, where a thermal component with the temperature kT = (517 {+-} 28) keV and a flux comparable with the non-thermal part of the spectrum is observed. This non-thermal component as well as the subsequent emission, where there is no evidence for a thermal spectrum, is identified with the extended afterglow. We deduce a theoretical cosmological redshift z = 1.61 {+-} 0.14. We then derive the total energy E{sup tot}{sub e{sup +}e{sup -}}= (2.83{+-}0.15) Multiplication-Sign 10{sup 53} erg, the baryon load B = (4.13 {+-} 0.05) Multiplication-Sign 10{sup -5}, the Lorentz {Gamma} factor at transparency {Gamma}{sub tr} = (1.44 {+-} 0.01) Multiplication-Sign 10{sup 4}, and the intrinsic duration {Delta}t' {approx} 0.35 s. We also determine the average density of the circumburst medium (CBM), (n {sub CBM}) = (1.90 {+-} 0.20) Multiplication-Sign 10{sup -5} particles cm{sup -3}. There is no evidence of beaming in the system. In view of the energetics and of the baryon load of the source, as well as of the low interstellar medium and of the intrinsic timescale of the signal, we identify the GRB progenitor as a binary neutron star. From the recent progress in the theory of neutron stars, we obtain

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

DOE PAGES

Abbott, B. P.; Abbott, R.; Abbott, T. D.; ...

2017-10-16

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance ismore » $$5.0\\times {10}^{-8}$$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $$(+1.74\\pm 0.05)\\,{\\rm{s}}$$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $$-3\\times {10}^{-15}$$ and $$+7\\times {10}^{-16}$$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.« less

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

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

Abbott, B. P.; Abbott, R.; Abbott, T. D.

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance ismore » $$5.0\\times {10}^{-8}$$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $$(+1.74\\pm 0.05)\\,{\\rm{s}}$$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $$-3\\times {10}^{-15}$$ and $$+7\\times {10}^{-16}$$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.« less

An Ordinary Short Gamma-Ray Burst with Extraordinary Implications: Fermi -GBM Detection of GRB 170817A

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

Goldstein, A.; Roberts, O. J.; Connaughton, V.

On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 1.7 s prior to this GRB, the Laser Interferometer Gravitational-wave Observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this ordinary short GRB, which extraordinarily confirms that at least some short GRBs are produced by binary compact mergers.

An Ordinary Short Gamma-Ray Burst with Extraordinary Implications: Fermi-GBM Detection of GRB 170817A

NASA Astrophysics Data System (ADS)

Goldstein, A.; Veres, P.; Burns, E.; Briggs, M. S.; Hamburg, R.; Kocevski, D.; Wilson-Hodge, C. A.; Preece, R. D.; Poolakkil, S.; Roberts, O. J.; Hui, C. M.; Connaughton, V.; Racusin, J.; von Kienlin, A.; Dal Canton, T.; Christensen, N.; Littenberg, T.; Siellez, K.; Blackburn, L.; Broida, J.; Bissaldi, E.; Cleveland, W. H.; Gibby, M. H.; Giles, M. M.; Kippen, R. M.; McBreen, S.; McEnery, J.; Meegan, C. A.; Paciesas, W. S.; Stanbro, M.

2017-10-01

On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 1.7 s prior to this GRB, the Laser Interferometer Gravitational-wave Observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this ordinary short GRB, which extraordinarily confirms that at least some short GRBs are produced by binary compact mergers.

Optical and Near-Infrared Observations of SN 2013DX Associated with GRB 130702A

NASA Technical Reports Server (NTRS)

Toy, V. L.; Cenko, S. B.; Silverman, J. M.; Butler, N. R.; Cucchiara, A.; Watson, A. M.; Bersier, D.; Perley, D. A.; Margutti, R.; Bellm, E.;

GRB 170817A as a jet counterpart to gravitational wave trigger GW 170817

NASA Astrophysics Data System (ADS)

Lamb, Gavin P.; Kobayashi, Shiho

2018-05-01

Fermi/GBM (Gamma-ray Burst Monitor) and INTEGRAL (the International Gamma-ray Astrophysics Laboratory) reported the detection of the γ-ray counterpart, GRB 170817A, to the LIGO (Light Interferometer Gravitational-wave Observatory)/Virgo gravitational wave detected binary neutron star merger, GW 170817. GRB 170817A is likely to have an internal jet or another origin such as cocoon emission, shock-breakout, or a flare from a viscous disc. In this paper we assume that the γ-ray emission is caused by energy dissipation within a relativistic jet and we model the afterglow synchrotron emission from a reverse- and forward-shock in the outflow. We show the afterglow for a low-luminosity γ-ray burst (GRB) jet with a high Lorentz-factor (Γ); a low-Γ and low-kinetic energy jet; a low-Γ, high kinetic energy jet; structured jets viewed at an inclination within the jet-half-opening angle; and an off-axis `typical' GRB jet. All jet models will produce observable afterglows on various timescales. The late-time afterglow from 10-110 days can be fit by a Gaussian structured jet viewed at a moderate inclination, however the GRB is not directly reproduced by this model. These jet afterglow models can be used for future GW detected NS merger counterparts with a jet afterglow origin.

A Strong Limit on the Very-high-energy Emission from GRB 150323A

NASA Astrophysics Data System (ADS)

Abeysekara, A. U.; Archer, A.; Benbow, W.; Bird, R.; Brose, R.; Buchovecky, M.; Bugaev, V.; Connolly, M. P.; Cui, W.; Errando, M.; Falcone, A.; Feng, Q.; Finley, J. P.; Flinders, A.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Hütten, M.; Hanna, D.; Hervet, O.; Holder, J.; Hughes, G.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Kieda, D.; Krause, M.; Krennrich, F.; Lang, M. J.; Lin, T. T. Y.; Maier, G.; McArthur, S.; Moriarty, P.; Mukherjee, R.; O’Brien, S.; Ong, R. A.; Park, N.; Perkins, J. S.; Petrashyk, A.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rulten, C.; Sadeh, I.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Tyler, J.; Wakely, S. P.; Weiner, O. M.; Weinstein, A.; Wells, R. M.; Wilcox, P.; Wilhelm, A.; Williams, D. A.; Zitzer, B.; VERITAS Collaboration; Vurm, Indrek; Beloborodov, Andrei

2018-04-01

On 2015 March 23, the Very Energetic Radiation Imaging Telescope Array System (VERITAS) responded to a Swift-Burst Alert Telescope (BAT) detection of a gamma-ray burst, with observations beginning 270 s after the onset of BAT emission, and only 135 s after the main BAT emission peak. No statistically significant signal is detected above 140 GeV. The VERITAS upper limit on the fluence in a 40-minute integration corresponds to about 1% of the prompt fluence. Our limit is particularly significant because the very-high-energy (VHE) observation started only ∼2 minutes after the prompt emission peaked, and Fermi-Large Area Telescope observations of numerous other bursts have revealed that the high-energy emission is typically delayed relative to the prompt radiation and lasts significantly longer. Also, the proximity of GRB 150323A (z = 0.593) limits the attenuation by the extragalactic background light to ∼50% at 100–200 GeV. We conclude that GRB 150323A had an intrinsically very weak high-energy afterglow, or that the GeV spectrum had a turnover below ∼100 GeV. If the GRB exploded into the stellar wind of a massive progenitor, the VHE non-detection constrains the wind density parameter to be A ≳ 3 × 1011 g cm‑1, consistent with a standard Wolf–Rayet progenitor. Alternatively, the VHE emission from the blast wave would be weak in a very tenuous medium such as the interstellar medium, which therefore cannot be ruled out as the environment of GRB 150323A.

CONSTRAINTS ON THE EMISSION MODEL OF THE 'NAKED-EYE BURST' GRB 080319B

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

Abdo, A. A.; Abeysekara, A. U.; Linnemann, J. T.

On 2008 March 19, one of the brightest gamma-ray bursts (GRBs) ever recorded was detected by several ground- and space-based instruments spanning the electromagnetic spectrum from radio to gamma rays. With a peak visual magnitude of 5.3, GRB 080319B was dubbed the 'naked-eye' GRB, as an observer under dark skies could have seen the burst without the aid of an instrument. Presented here are results from observations of the prompt phase of GRB 080319B taken with the Milagro TeV observatory. The burst was observed at an elevation angle of 47 Degree-Sign . Analysis of the data is performed using bothmore » the standard air shower method and the scaler or single-particle technique, which results in a sensitive energy range that extends from {approx}5 GeV to >20 TeV. These observations provide the only direct constraints on the properties of the high-energy gamma-ray emission from GRB 080319B at these energies. No evidence for emission is found in the Milagro data, and upper limits on the gamma-ray flux above 10 GeV are derived. The limits on emission between {approx}25 and 200 GeV are incompatible with the synchrotron self-Compton model of gamma-ray production and disfavor a corresponding range (2 eV-16 eV) of assumed synchrotron peak energies. This indicates that the optical photons and soft ({approx}650 keV) gamma rays may not be produced by the same electron population.« less

GRB host galaxies with VLT/X-Shooter: properties at 0.8 < z < 1.3

NASA Astrophysics Data System (ADS)

Piranomonte, S.; Japelj, J.; Vergani, S. D.; Savaglio, S.; Palazzi, E.; Covino, S.; Flores, H.; Goldoni, P.; Cupani, G.; Krühler, T.; Mannucci, F.; Onori, F.; Rossi, A.; D'Elia, V.; Pian, E.; D'Avanzo, P.; Gomboc, A.; Hammer, F.; Randich, S.; Fiore, F.; Stella, L.; Tagliaferri, G.

2015-10-01

Long gamma-ray bursts (LGRBs) are associated with the death of massive stars. Their host galaxies therefore represent a unique class of objects tracing star formation across the observable Universe. Indeed, recently accumulated evidence shows that GRB hosts do not differ substantially from general population of galaxies at high (z > 2) redshifts. However, it has been long recognized that the properties of z < 1.5 hosts, compared to general star-forming population, are unusual. To better understand the reasons for the supposed difference in LGRB hosts properties at z < 1.5, we obtained Very Large Telescope (VLT)/X-Shooter spectra of six hosts lying in the redshift range of 0.8 < z < 1.3. Some of these hosts have been observed before, yet we still lack well-constrained information on their characteristics such as metallicity, dust extinction and star formation rate (SFR). We search for emission lines in the VLT/X-Shooter spectra of the hosts and measure their fluxes. We perform a detailed analysis, estimating host average extinction, SFRs, metallicities and electron densities where possible. Measured quantities of our hosts are compared to a larger sample of previously observed GRB hosts at z < 2. SFRs and metallicities are measured for all the hosts analysed in this paper and metallicities are well determined for four hosts. The mass-metallicity relation, the fundamental metallicity relation and SFRs derived from our hosts occupy similar parameter space as other host galaxies investigated so far at the same redshift. We therefore conclude that GRB hosts in our sample support the found discrepancy between the properties of low-redshift GRB hosts and the general population of star-forming galaxies.

A cross-correlation search for intermediate-duration gravitational waves from GRB magnetars

NASA Astrophysics Data System (ADS)

Coyne, Robert

2015-04-01

Since the discovery of the afterglow in 1997, the progress made in our understanding of gamma-ray bursts (GRBs) has been spectacular. Yet a direct proof of GRB progenitors is still missing. In the last few years, evidence for a long-lived and sustained central engine in GRBs has mounted. This has called attention to the so-called millisecond-magnetar model, which proposes that a highly magnetized, rapidly-rotating neutron star may exist at the heart of some of these events. The advent of advanced gravitational wave detectors such as LIGO and Virgo may enable us to probe directly, for the first time, the nature of GRB progenitors and their byproducts. In this context, we describe a novel application of a generalized cross-correlation technique optimized for the detection of long-duration gravitational wave signals that may be associated with bar-like deformations of GRB magnetars. The detection of these signals would allow us to answer some of the most intriguing questions on the nature of GRB progenitors, and serve as a starting point for a new class of intermediate-duration gravitational wave searches.

Early-Time Observations of the GRB 050319 Optical Transient

NASA Astrophysics Data System (ADS)

Quimby, R. M.; Rykoff, E. S.; Yost, S. A.; Aharonian, F.; Akerlof, C. W.; Alatalo, K.; Ashley, M. C. B.; Göǧüş, E.; Güver, T.; Horns, D.; Kehoe, R. L.; Kιzιloǧlu, Ü.; Mckay, T. A.; Özel, M.; Phillips, A.; Schaefer, B. E.; Smith, D. A.; Swan, H. F.; Vestrand, W. T.; Wheeler, J. C.; Wren, J.

2006-03-01

We present the unfiltered ROTSE-III light curve of the optical transient associated with GRB 050319 beginning 4 s after the cessation of γ-ray activity. We fit a power-law function to the data using the revised trigger time given by Chincarini and coworkers, and a smoothly broken power-law to the data using the original trigger disseminated through the GCN notices. Including the RAPTOR data from Woźniak and coworkers, the best-fit power-law indices are α=-0.854+/-0.014 for the single power-law and α1=-0.364+0.020-0.019, α2=-0.881+0.030-0.031, with a break at tb=418+31-30 s for the smoothly broken fit. We discuss the fit results, with emphasis placed on the importance of knowing the true start time of the optical transient for this multipeaked burst. As Swift continues to provide prompt GRB locations, it becomes more important to answer the question, ``when does the afterglow begin?'' in order to correctly interpret the light curves.

Mutation of a cuticular protein, BmorCPR2, alters larval body shape and adaptability in silkworm, Bombyx mori.

PubMed

Qiao, Liang; Xiong, Gao; Wang, Ri-xin; He, Song-zhen; Chen, Jie; Tong, Xiao-ling; Hu, Hai; Li, Chun-lin; Gai, Ting-ting; Xin, Ya-qun; Liu, Xiao-fan; Chen, Bin; Xiang, Zhong-huai; Lu, Cheng; Dai, Fang-yin

2014-04-01

Cuticular proteins (CPs) are crucial components of the insect cuticle. Although numerous genes encoding cuticular proteins have been identified in known insect genomes to date, their functions in maintaining insect body shape and adaptability remain largely unknown. In the current study, positional cloning led to the identification of a gene encoding an RR1-type cuticular protein, BmorCPR2, highly expressed in larval chitin-rich tissues and at the mulberry leaf-eating stages, which is responsible for the silkworm stony mutant. In the Dazao-stony strain, the BmorCPR2 allele is a deletion mutation with significantly lower expression, compared to the wild-type Dazao strain. Dysfunctional BmorCPR2 in the stony mutant lost chitin binding ability, leading to reduced chitin content in larval cuticle, limitation of cuticle extension, abatement of cuticle tensile properties, and aberrant ratio between internodes and intersegmental folds. These variations induce a significant decrease in cuticle capacity to hold the growing internal organs in the larval development process, resulting in whole-body stiffness, tightness, and hardness, bulging intersegmental folds, and serious defects in larval adaptability. To our knowledge, this is the first study to report the corresponding phenotype of stony in insects caused by mutation of RR1-type cuticular protein. Our findings collectively shed light on the specific role of cuticular proteins in maintaining normal larval body shape and will aid in the development of pest control strategies for the management of Lepidoptera.

An Evolving GeV Spectrum from Prompt to Afterglow: The Case of GRB 160509A

NASA Astrophysics Data System (ADS)

Tam, Pak-Hin Thomas; He, Xin-Bo; Tang, Qing-Wen; Wang, Xiang-Yu

2017-07-01

We present the high-energy emission properties of GRB 160509A, from its prompt mission to late afterglow phase. GRB 160509A contains two emission episodes: 0-40 s and 280-420 s after the burst onset ({t}0). The relatively high fluence of GRB 160509A allows us to establish an evolving spectrum above 100 MeV. During the first emission episode, the >100 MeV spectrum is soft with Γ ≥ 3.0, which can be smoothly connected to keV energies with a Band function with or without a high-energy cutoff. The >100 MeV spectrum rapidly changes to a hard spectrum with Γ ≤ 1.5 after {t}0+40 s. The existence of very energetic photons, e.g., a 52 GeV that arrives at {t}0+77 s and a 29 GeV that arrives at {t}0+70 ks, is hard to reconcile by the synchrotron emission from forward-shock electrons, but is likely due to an inverse-Compton (IC) mechanism (e.g., synchrotron self-Compton emission). A soft spectrum (Γ ˜ 2) between 300 and 1000 s after the burst onset is also found at a significance of about 2 standard deviations, which suggests a different emission mechanism at work for this short period of time. GRB 160509A represents the latest example where IC emission has to be taken into account in explaining the afterglow GeV emission, which had been suggested long before the launch of the Fermi Large Area Telescope.

Exploring the Cosmic Dawn, Galaxy Evolution, and Exotic Stellar Deaths with Rapid GRB Follow-Up Observations

NASA Astrophysics Data System (ADS)

Berger, Edo; Cenko, Stephen; Schmidt, Brian; Perley, Daniel; Berger, Edo; Fox, Derek; Fruchter, Andrew; Bloom, Joshua; Prochaska, Jason X.; Lopez, Sebastian; Cobb, Bethany; Roth, Kathy; Levan, Andrew; Tanvir, Nial; Rapoport, Sharon; Yuan, Fang; Chornock, Ryan; Wen-Fai, Fong; Morgan, Adam; Wiersema, Klaas; Cucchiara, Antonino

2013-08-01

The study of gamma-ray burst (GRB) afterglows, host galaxies, and associated supernovae (SNe) sheds light on a wide range of open questions in astrophysics, ranging from the deaths of massive stars to cosmic chemical enrichment and the reionization epoch, and soon, the electromagnetic (EM) counterparts of gravitational wave (GW) sources. Over the past decade, Gemini has played a leading role in all aspects of GRB science through its combination of rapid-response spectroscopy and imaging coupled with deep late-time host galaxy, afterglow, and GRB-SN follow-up. Here, we propose to step forward in our long-standing program of ToO observations, with this proposal focusing on "Rapid ToO" science, observations at t <˜ 1 day. In conjunction with an array of multi-wavelength EM facilities, we focus on three key science topics: (1) Identification, characterization, and exploitation of high-redshift GRBs in order to study the evolving IGM and galaxy populations at these redshifts; (2) Studies of short GRB afterglows and their environments to yield insight into the nature of their progenitor population, for connection with forthcoming GW facilities; and (3) Observation of exceptionally energetic bursts detected by the Fermi-LAT instrument, to test models of burst engines and enable their use as testbeds for quantum gravity effects.

Exploring the Cosmic Dawn, Galaxy Evolution, and Exotic Stellar Deaths with Rapid GRB Follow-Up Observations

NASA Astrophysics Data System (ADS)

Berger, Edo; Fox, Derek; Chornock, Ryan; Fong, Wen-Fai; Cobb, Bethany; Cenko, Brad; Perley, Daniel; Bloom, Joshua; Prochaska, Jason X.; Morgan, Adam; Cucchiara, Antonino; Levan, Andrew; Tanvir, Nial; Fruchter, Andrew; Lopez, Sebastian; Wiersema, Klaas; Roth, Kathy

2014-02-01

The study of gamma-ray burst (GRB) afterglows, host galaxies, and associated supernovae (SNe) sheds light on a wide range of open questions in astrophysics, ranging from the deaths of massive stars to cosmic chemical enrichment and the reionization epoch, and soon, the electromagnetic (EM) counterparts of gravitational wave (GW) sources. Over the past decade, Gemini has played a leading role in all aspects of GRB science through its combination of rapid-response spectroscopy and imaging coupled with deep late-time host galaxy, afterglow, and GRB-SN follow-up. Here, we propose to step forward in our long-standing program of ToO observations, with this proposal focusing on "Rapid ToO" science, observations at t <˜ 1 day. In conjunction with an array of multi-wavelength EM facilities, we focus on three key science topics: (1) Identification, characterization, and exploitation of high-redshift GRBs in order to study the evolving IGM and galaxy populations at these redshifts; (2) Studies of short GRB afterglows and their environments to yield insight into the nature of their progenitor population, for connection with forthcoming GW facilities; and (3) Observation of exceptionally energetic bursts detected by the Fermi-LAT instrument, to test models of burst engines and enable their use as testbeds for quantum gravity effects.

Implications for the Origin of GRB 051103 from LIGO Observations

NASA Technical Reports Server (NTRS)

Bizouard, M. A.; Dietz, A.; Guidi, G. M.; Was, M.; Camp, J. B.; Cannizzo, J.; Stroeer, A. S.; Blackburn, L.

2012-01-01

We present the results of a LIGO search for gravitational waves (GWs) associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst whose electromagnetically determined sky position is coincident with the spiral galaxy M81, which is 3.6Mpc from Earth. Possible progenitors for short-hard GRBs include compact object mergers and soft gamma repeater (SGR) giant flares. A merger progenitor would produce a characteristic GW signal that should be detectable at the distance of M81, while GW emission from an SGR is not expected to be detectable at that distance. We found no evidence of a GW signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission with a jet semi-angle of 30. we exclude a binary neutron star merger in M81 as the progenitor with a confidence of 98%. Neutron star-black hole mergers are excluded with > 99% confidence. If the event occurred in M81 our findings support the hypothesis that GRB 051103 was due to an SGR giant flare, making it the most distant extragalactic magnetar observed to date.

MAGIC upper limits on the GRB 090102 afterglow

DOE PAGES

Aleksic, J.; Ansoldi, S.; Antonelli, L. A.; ...

2013-12-09

Indications of a GeV component in the emission from gamma-ray bursts (GRBs) are known since the Energetic Gamma-Ray Experiment Telescope observations during the 1990s and they have been confirmed by the data of the Fermi satellite. Our results have, however, shown that our understanding of GRB physics is still unsatisfactory. The new generation of Cherenkov observatories and in particular the MAGIC telescope, allow for the first time the possibility to extend the measurement of GRBs from several tens up to hundreds of GeV energy range. Both leptonic and hadronic processes have been suggested to explain the possible GeV/TeV counterpart ofmore » GRBs. Observations with ground-based telescopes of very high energy (VHE) photons (E > 30 GeV) from these sources are going to play a key role in discriminating among the different proposed emission mechanisms, which are barely distinguishable at lower energies. MAGIC telescope observations of the GRB 090102 (z = 1.547) field and Fermi Large Area Telescope data in the same time interval are analysed to derive upper limits of the GeV/TeV emission. We compare these results to the expected emissions evaluated for different processes in the framework of a relativistic blastwave model for the afterglow. Simultaneous upper limits with Fermi and a Cherenkov telescope have been derived for this GRB observation. We obtained results compatible with the expected emission although the difficulties in predicting the HE and VHE emission for the afterglow of this event makes it difficult to draw firmer conclusions. Nonetheless, MAGIC sensitivity in the energy range of overlap with space-based instruments (above about 40 GeV) is about one order of magnitude better with respect to Fermi. This makes evident the constraining power of ground-based observations and shows that the MAGIC telescope has reached the required performance to make possible GRB multiwavelength studies in the VHE range.« less

Adapter reagents for protein site specific dye labeling.

PubMed

Thompson, Darren A; Evans, Eric G B; Kasza, Tomas; Millhauser, Glenn L; Dawson, Philip E

2014-05-01

Chemoselective protein labeling remains a significant challenge in chemical biology. Although many selective labeling chemistries have been reported, the practicalities of matching the reaction with appropriately functionalized proteins and labeling reagents is often a challenge. For example, we encountered the challenge of site specifically labeling the cellular form of the murine Prion protein with a fluorescent dye. To facilitate this labeling, a protein was expressed with site specific p-acetylphenylalanine. However, the utility of this acetophenone reactive group is hampered by the severe lack of commercially available aminooxy fluorophores. Here we outline a general strategy for the efficient solid phase synthesis of adapter reagents capable of converting maleimido-labels into aminooxy or azide functional groups that can be further tuned for desired length or solubility properties. The utility of the adapter strategy is demonstrated in the context of fluorescent labeling of the murine Prion protein through an adapted aminooxy-Alexa dye. © 2014 Wiley Periodicals, Inc.

Adapter Reagents for Protein Site Specific Dye Labeling

PubMed Central

Thompson, Darren A.; Evans, Eric G. B.; Kasza, Tomas; Millhauser, Glenn L.; Dawson, Philip E.

2016-01-01

Chemoselective protein labeling remains a significant challenge in chemical biology. Although many selective labeling chemistries have been reported, the practicalities of matching the reaction with appropriately functionalized proteins and labeling reagents is often a challenge. For example, we encountered the challenge of site specifically labeling the cellular form of the murine Prion protein with a fluorescent dye. To facilitate this labeling, a protein was expressed with site specific p-acetylphenylalanine. However, the utility of this aceto-phenone reactive group is hampered by the severe lack of commercially available aminooxy fluorophores. Here we outline a general strategy for the efficient solid phase synthesis of adapter reagents capable of converting maleimido-labels into aminooxy or azide functional groups that can be further tuned for desired length or solubility properties. The utility of the adapter strategy is demonstrated in the context of fluorescent labeling of the murine Prion protein through an adapted aminooxy-Alexa dye. PMID:24599728

The Origin of the Optical Flashes: The Case Study of GRB 080319B and GRB 130427A

NASA Astrophysics Data System (ADS)

Fraija, N.; Veres, P.

2018-05-01

Correlations between optical flashes and gamma-ray emissions in gamma-ray bursts (GRBs) have been searched in order to clarify the question of whether these emissions occur at internal and/or external shocks. Among the most powerful GRBs ever recorded are GRB 080319B and GRB 130427A, which at early phases presented bright optical flashes possibly correlated with γ-ray components. Additionally, both bursts were fortuitously located within the field of view of the TeV γ-ray Milagro and HAWC observatories, and although no statistically significant excess of counts were collected, upper limits were placed on the GeV–TeV emission. Considering the synchrotron self-Compton emission from internal shocks and requiring the GeV–TeV upper limits, we found that the optical flashes and the γ-ray components are produced by different electron populations. Analyzing the optical flashes together with the multiwavelength afterglow observation, we found that these flashes can be interpreted in the framework of the synchrotron reverse shock model when outflows have arbitrary magnetizations.

GRB 091127: The Cooling Break Race on Magnetic Fuel

NASA Technical Reports Server (NTRS)

Filgas, R.; Greiner, J.; Schady, P.; Kruhler, T.; Updike, A. C.; Klose, S.; Nardini, M.; Kann, D. A.; Rossi, A.; Sudilovsky, V.;

BATSE analysis techniques for probing the GRB spatial and luminosity distributions

NASA Technical Reports Server (NTRS)

Hakkila, Jon; Meegan, Charles A.

1992-01-01

The Burst And Transient Source Experiment (BATSE) has measured homogeneity and isotropy parameters from an increasingly large sample of observed gamma-ray bursts (GRBs), while also maintaining a summary of the way in which the sky has been sampled. Measurement of both of these are necessary for any study of the BATSE data statistically, as they take into account the most serious observational selection effects known in the study of GRBs: beam-smearing and inhomogeneous, anisotropic sky sampling. Knowledge of these effects is important to analysis of GRB angular and intensity distributions. In addition to determining that the bursts are local, it is hoped that analysis of such distributions will allow boundaries to be placed on the true GRB spatial distribution and luminosity function. The technique for studying GRB spatial and luminosity distributions is direct. Results of BATSE analyses are compared to Monte Carlo models parameterized by a variety of spatial and luminosity characteristics.

Differential protein expression during colonic adaptation in ultra-short bowel rats

PubMed Central

Jiang, Hai-Ping; Chen, Tao; Yan, Guang-Rong; Chen, Dan

2011-01-01

AIM: To investigate the proteins involved in colonic adaptation and molecular mechanisms of colonic adaptation in rats with ultra-short bowel syndrome (USBS). METHODS: Sprague Dawley rats were randomly assigned to three groups: USBS group (10 rats) undergoing an approximately 90%-95% small bowel resection; sham-operation group (10 rats) undergoing small bowel transaction and anastomosis; and control group (ten normal rats). Colon morphology and differential protein expression was analyzed after rats were given post-surgical enteral nutrition for 21 d. Protein expression in the colonic mucosa was analyzed by two-dimensional electrophoresis (2-DE) in all groups. Differential protein spots were detected by ImageMaster 2D Platinum software and were further analyzed with matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometric (MALDI-TOF/TOF-MS) analysis. RESULTS: The colonic mucosal thickness significantly increased in the USBS group compared with the control group (302.1 ± 16.9 μm vs 273.7 ± 16.0 μm, P < 0.05). There was no statistically significant difference between the sham-operation group and control group (P > 0.05). The height of colon plica markedly improved in USBS group compared with the control group (998.4 ± 81.2 μm vs 883.4 ± 39.0 μm, P < 0.05). There was no statistically significant difference between the sham-operation and control groups (P > 0.05). A total of 141 differential protein spots were found in the USBS group. Forty-nine of these spots were down-regulated while 92 protein spots were up-regulated by over 2-folds. There were 133 differential protein spots in USBS group. Thirty of these spots were down-regulated and 103 were up-regulated. There were 47 common differential protein spots among the three groups, including 17 down-regulated protein spots and 30 up-regulated spots. Among 47 differential spots, eight up-regulated proteins were identified by MALDI-TOF/TOF-MS. These proteins were previously

Differential protein expression during colonic adaptation in ultra-short bowel rats.

PubMed

Jiang, Hai-Ping; Chen, Tao; Yan, Guang-Rong; Chen, Dan

2011-05-28

To investigate the proteins involved in colonic adaptation and molecular mechanisms of colonic adaptation in rats with ultra-short bowel syndrome (USBS). Sprague Dawley rats were randomly assigned to three groups: USBS group (10 rats) undergoing an approximately 90%-95% small bowel resection; sham-operation group (10 rats) undergoing small bowel transaction and anastomosis; and control group (ten normal rats). Colon morphology and differential protein expression was analyzed after rats were given post-surgical enteral nutrition for 21 d. Protein expression in the colonic mucosa was analyzed by two-dimensional electrophoresis (2-DE) in all groups. Differential protein spots were detected by ImageMaster 2D Platinum software and were further analyzed with matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometric (MALDI-TOF/TOF-MS) analysis. The colonic mucosal thickness significantly increased in the USBS group compared with the control group (302.1 ± 16.9 μm vs 273.7 ± 16.0 μm, P < 0.05). There was no statistically significant difference between the sham-operation group and control group (P > 0.05). The height of colon plica markedly improved in USBS group compared with the control group (998.4 ± 81.2 μm vs 883.4 ± 39.0 μm, P < 0.05). There was no statistically significant difference between the sham-operation and control groups (P > 0.05). A total of 141 differential protein spots were found in the USBS group. Forty-nine of these spots were down-regulated while 92 protein spots were up-regulated by over 2-folds. There were 133 differential protein spots in USBS group. Thirty of these spots were down-regulated and 103 were up-regulated. There were 47 common differential protein spots among the three groups, including 17 down-regulated protein spots and 30 up-regulated spots. Among 47 differential spots, eight up-regulated proteins were identified by MALDI-TOF/TOF-MS. These proteins were previously reported to be involved in

Membrane Targeting of Grb2-associated Binder-1 (Gab1) Scaffolding Protein through Src Myristoylation Sequence Substitutes for Gab1 Pleckstrin Homology Domain and Switches an Epidermal Growth Factor Response to an Invasive Morphogenic Program

PubMed Central

Maroun, Christiane R.; Naujokas, Monica A.; Park, Morag

2003-01-01

The hepatocyte growth factor receptor tyrosine kinase Met promotes cell dissociation and the inherent morphogenic program of epithelial cells. In a search for substrates downstream from Met, we have previously identified the Grb2-associated binder-1 (Gab1) as critical for the morphogenic program. Gab1 is a scaffold protein that acts to diversify the signal downstream from the Met receptor through its ability to couple with multiple signal transduction pathways. Gab1 contains a pleckstrin homology (PH) domain with specificity for phosphatidylinositol 3,4,5-trisphosphate. The phospholipid binding capacity of the Gab1 PH domain is required for the localization of Gab1 at sites of cell-cell contact in colonies of epithelial cells and for epithelial morphogenesis, suggesting that PH domain-dependent subcellular localization of Gab1 is a prerequisite for function. We have investigated the requirement for membrane localization of Gab1 for biological activity. We show that substitution of the Gab1 PH domain with the myristoylation signal from the c-Src protein is sufficient to replace the Gab1 PH domain for epithelial morphogenesis. The membrane targeting of Gab1 enhances Rac activity in the absence of stimulation and switches a nonmorphogenic noninvasive response to epidermal growth factor to a morphogenic invasive program. These results suggest that the subcellular localization of Gab1 is a critical determinant for epithelial morphogenesis and invasiveness. PMID:12686619

Relativistic Hydrodynamics and Spectral Evolution of GRB Jets

NASA Astrophysics Data System (ADS)

Cuesta-Martínez, C.

2017-09-01

In this thesis we study the progenitor systems of long gamma-ray bursts (GRBs) using numerical models of their dynamics and the electromagnetic emission. Of all the possible classes of events, we focus on those showing a prominent component of thermal emission, which might be generated due to the interaction of a relativistic jet with the medium into which it is propagating. The main part of the thesis is devoted to modelling GRBs from two different clases of progenitors: ultra-long GRBs dominated by blackbody emission and GRBs associated with core-collapse supernovae (SNe). The study of GRB jets and their radiative emission has been basically divided into two steps. First, the dynamical evolution of relativistic jets can be simulated by means of multidimensional special relativistic hydrodynamic simulations which have been performed with the MRGENESIS code. Second, the synthetic emission from such jets is computed with the relativistic radiative transfer code SPEV in a post-processing stage assuming different radiative processes in which we follow the temporal and spectral evolution of the emitted radiation. An instrumental part of this project consisted in extending SPEV to include thermal processes, such as thermal bremsstrahlung, in order to account for the thermal signal that may arise in some GRBs. In the first part of this thesis, we extend an existing theoretical model to explain the class of blackbody-dominated GRBs (BBD-GRBs), i.e., long lasting events characterized by the presence of a notable thermal component trailing the GRB prompt emission, and a rather weak traditional afterglow. GRB 101225A, the "Christmas burst", is the most prominent member of this class. It has been suggested that BBD-GRBs could result from the merger of a binary system formed by a neutron star and the Helium core of an evolved, massive star. We model in 2D the propagation of ultrarelativistic jets through the environments created by such mergers. We outline the most relevant

GRB 060505: A Possible Short-Duration Gamma-Ray Burst in a Star Forming Region at Redshift of 0.09

NASA Technical Reports Server (NTRS)

Ofek, E. O.; Cenko, S. B.; Gal-Yam, A.; Fox, D. B.; Nakar, E.; Rau, A.; Frail, D. A.; Kullkarni, S. R.; Price, P. A.; Schmidt, B. P.;

Adaptive evolution of centromere proteins in plants and animals.

PubMed

Talbert, Paul B; Bryson, Terri D; Henikoff, Steven

2004-01-01

Centromeres represent the last frontiers of plant and animal genomics. Although they perform a conserved function in chromosome segregation, centromeres are typically composed of repetitive satellite sequences that are rapidly evolving. The nucleosomes of centromeres are characterized by a special H3-like histone (CenH3), which evolves rapidly and adaptively in Drosophila and Arabidopsis. Most plant, animal and fungal centromeres also bind a large protein, centromere protein C (CENP-C), that is characterized by a single 24 amino-acid motif (CENPC motif). Whereas we find no evidence that mammalian CenH3 (CENP-A) has been evolving adaptively, mammalian CENP-C proteins contain adaptively evolving regions that overlap with regions of DNA-binding activity. In plants we find that CENP-C proteins have complex duplicated regions, with conserved amino and carboxyl termini that are dissimilar in sequence to their counterparts in animals and fungi. Comparisons of Cenpc genes from Arabidopsis species and from grasses revealed multiple regions that are under positive selection, including duplicated exons in some grasses. In contrast to plants and animals, yeast CENP-C (Mif2p) is under negative selection. CENP-Cs in all plant and animal lineages examined have regions that are rapidly and adaptively evolving. To explain these remarkable evolutionary features for a single-copy gene that is needed at every mitosis, we propose that CENP-Cs, like some CenH3s, suppress meiotic drive of centromeres during female meiosis. This process can account for the rapid evolution and the complexity of centromeric DNA in plants and animals as compared to fungi.

In vivo functional mapping of the conserved protein domains within murine Themis1.

PubMed

Zvezdova, Ekaterina; Lee, Jan; El-Khoury, Dalal; Barr, Valarie; Akpan, Itoro; Samelson, Lawrence; Love, Paul E

2014-09-01

Thymocyte development requires the coordinated input of signals that originate from numerous cell surface molecules. Although the majority of thymocyte signal-initiating receptors are lineage-specific, most trigger 'ubiquitous' downstream signaling pathways. T-lineage-specific receptors are coupled to these signaling pathways by lymphocyte-restricted adapter molecules. We and others recently identified a new putative adapter protein, Themis1, whose expression is largely restricted to the T lineage. Mice lacking Themis1 exhibit a severe block in thymocyte development and a striking paucity of mature T cells revealing a critical role for Themis1 in T-cell maturation. Themis1 orthologs contain three conserved domains: a proline-rich region (PRR) that binds to the ubiquitous cytosolic adapter Grb2, a nuclear localization sequence (NLS), and two copies of a novel cysteine-containing globular (CABIT) domain. In the present study, we evaluated the functional importance of each of these motifs by retroviral reconstitution of Themis1(-/-) progenitor cells. The results demonstrate an essential requirement for the PRR and NLS motifs but not the conserved CABIT cysteines for Themis1 function.

Time-dependent Optical Spectroscopy of GRB 010222: Clues to the Gamma-Ray Burst Environment

NASA Astrophysics Data System (ADS)

Mirabal, N.; Halpern, J. P.; Kulkarni, S. R.; Castro, S.; Bloom, J. S.; Djorgovski, S. G.; Galama, T. J.; Harrison, F. A.; Frail, D. A.; Price, P. A.; Reichart, D. E.; Ebeling, H.; Bunker, A.; Dawson, S.; Dey, A.; Spinrad, H.; Stern, D.

2002-10-01

We present sequential optical spectra of the afterglow of GRB 010222 obtained 1 day apart using the Low-Resolution Imaging Spectrometer (LRIS) and the Echellette Spectrograph and Imager (ESI) on the Keck Telescopes. Three low-ionization absorption systems are spectroscopically identified at z1=1.47688, z2=1.15628, and z3=0.92747. The higher resolution ESI spectrum reveals two distinct components in the highest redshift system at z1a=1.47590 and z1b=1.47688. We interpret the z1b=1.47688 system as an absorption feature of the disk of the host galaxy of GRB 010222. The best-fitted power-law optical continuum and [Zn/Cr] ratio imply low dust content or a local gray dust component near the burst site. In addition, we do not detect strong signatures of vibrationally excited states of H2. If the gamma-ray burst took place in a superbubble or young stellar cluster, there are no outstanding signatures of an ionized absorber either. Analysis of the spectral time dependence at low resolution shows no significant evidence for absorption-line variability. This lack of variability is confronted with time-dependent photoionization simulations designed to apply the observed flux from GRB 010222 to a variety of assumed atomic gas densities and cloud radii. The absence of time dependence in the absorption lines implies that high-density environments are disfavored. In particular, if the GRB environment was dust free, its density was unlikely to exceed nHI=102 cm-3. If depletion of metals onto dust is similar to Galactic values or less than solar abundances are present, then nHI>=2×104 cm-3 is probably ruled out in the immediate vicinity of the burst. Based on data obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA and was made possible with the generous financial support of the W. M. Keck Foundation.

THE UNUSUAL RADIO AFTERGLOW OF THE ULTRA-LONG GAMMA-RAY BURST GRB 130925A

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

Horesh, Assaf; Cenko, S. Bradley; Perley, Daniel A.

2015-10-10

GRB 130925A is one of the recent additions to the growing family of ultra-long gamma-ray bursts (GRBs; T90 ≳1000 s). While the X-ray emission of ultra-long GRBs have been studied extensively in the past, no comprehensive radio data set has been obtained so far. We report here the early discovery of an unusual radio afterglow associated with the ultra-long GRB 130925A. The radio emission peaks at low-frequencies (∼7 GHz) at early times, only 2.2 days after the burst occurred. More notably, the radio spectrum at frequencies above 10 GHz exhibits a rather steep cut-off, compared to other long GRB radiomore » afterglows. This cut-off can be explained if the emitting electrons are either mono-energetic or originate from a rather steep, dN/dE ∝ E{sup −4}, power-law energy distribution. An alternative electron acceleration mechanism may be required to produce such an electron energy distribution. Furthermore, the radio spectrum exhibits a secondary underlying and slowly varying component. This may hint that the radio emission we observed is comprised of emission from both a reverse and a forward shock. We discuss our results in comparison with previous works that studied the unusual X-ray spectrum of this event and discuss the implications of our findings on progenitor scenarios.« less

Engineering of Bispecific Affinity Proteins with High Affinity for ERBB2 and Adaptable Binding to Albumin

PubMed Central

Nilvebrant, Johan; Åstrand, Mikael; Georgieva-Kotseva, Maria; Björnmalm, Mattias; Löfblom, John; Hober, Sophia

2014-01-01

The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein. PMID:25089830

The Ultra-long GRB 111209A. II. Prompt to Afterglow and Afterglow Properties

NASA Astrophysics Data System (ADS)

Stratta, G.; Gendre, B.; Atteia, J. L.; Boër, M.; Coward, D. M.; De Pasquale, M.; Howell, E.; Klotz, A.; Oates, S.; Piro, L.

2013-12-01

The "ultra-long" gamma-ray burst GRB 111209A at redshift z = 0.677 is the longest GRB ever observed thus far, with a rest frame prompt emission duration of ~4 hr. In order to explain the burst exceptional longevity, a low-metallicity blue supergiant progenitor was invoked. In this article we further constrain the phenomenology and progenitor properties of this peculiar GRB by performing a multiband temporal and spectral analysis of both the prompt and the afterglow emission. We use proprietary and publicly available data from Swift, Konus WIND, XMM-Newton, and TAROT, as well as from other ground-based optical and radio telescopes. We find some peculiar properties that are possibly connected to the exceptional nature of this burst, namely: (1) an unprecedented large optical delay of 410 ± 50 s between the peak time in gamma-rays and the peak time in the optical of a marked multiwavelength flare; (2) multiwavelength prompt emission spectral modeling requires a certain amount of dust in the circumburst environment. The dust produces a rest frame visual extinction of AV = 0.3-1.5 mag, and may undergo destruction at late times; and (3) we detect the presence of a hard spectral extra power-law component at the end of the X-ray steep steep decay phase and before the start of the X-ray afterglow, which has never been revealed thus far in past GRBs. The optical afterglow shows more usual properties; it has a flux power-law decay with an index of 1.6 ± 0.1 and a late rebrightening feature observed at ~1.1 the day after the first Burst Alert Telescope trigger. We discuss our findings in the context of several possible interpretations that have been given thus far of the complex multiband GRB phenomenology and propose a binary channel formation for the blue supergiant progenitor.

GRB 110715A: the peculiar multiwavelength evolution of the first afterglow detected by ALMA

NASA Astrophysics Data System (ADS)

Sánchez-Ramírez, R.; Hancock, P. J.; Jóhannesson, G.; Murphy, Tara; de Ugarte Postigo, A.; Gorosabel, J.; Kann, D. A.; Krühler, T.; Oates, S. R.; Japelj, J.; Thöne, C. C.; Lundgren, A.; Perley, D. A.; Malesani, D.; de Gregorio Monsalvo, I.; Castro-Tirado, A. J.; D'Elia, V.; Fynbo, J. P. U.; Garcia-Appadoo, D.; Goldoni, P.; Greiner, J.; Hu, Y.-D.; Jelínek, M.; Jeong, S.; Kamble, A.; Klose, S.; Kuin, N. P. M.; Llorente, A.; Martín, S.; Nicuesa Guelbenzu, A.; Rossi, A.; Schady, P.; Sparre, M.; Sudilovsky, V.; Tello, J. C.; Updike, A.; Wiersema, K.; Zhang, B.-B.

2017-02-01

We present the extensive follow-up campaign on the afterglow of GRB 110715A at 17 different wavelengths, from X-ray to radio bands, starting 81 s after the burst and extending up to 74 d later. We performed for the first time a GRB afterglow observation with the ALMA observatory. We find that the afterglow of GRB 110715A is very bright at optical and radio wavelengths. We use the optical and near-infrared spectroscopy to provide further information about the progenitor's environment and its host galaxy. The spectrum shows weak absorption features at a redshift z = 0.8225, which reveal a host-galaxy environment with low ionization, column density, and dynamical activity. Late deep imaging shows a very faint galaxy, consistent with the spectroscopic results. The broad-band afterglow emission is modelled with synchrotron radiation using a numerical algorithm and we determine the best-fitting parameters using Bayesian inference in order to constrain the physical parameters of the jet and the medium in which the relativistic shock propagates. We fitted our data with a variety of models, including different density profiles and energy injections. Although the general behaviour can be roughly described by these models, none of them are able to fully explain all data points simultaneously. GRB 110715A shows the complexity of reproducing extensive multiwavelength broad-band afterglow observations, and the need of good sampling in wavelength and time and more complex models to accurately constrain the physics of GRB afterglows.

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

PubMed

Hursel, Rick; Martens, Eveline A P; Gonnissen, Hanne K J; Hamer, Henrike M; Senden, Joan M G; van Loon, Luc J C; Westerterp-Plantenga, Margriet S

2015-01-01

Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0

GRB110721A: An Extreme Peak Energy and Signatures of the Photosphere

NASA Technical Reports Server (NTRS)

Axelsson, M.; Baldini, L.; Barbiellini, G.; Baring, M. G.; Bellazzini, R.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Caliandro, G. A.;

PLD2 has both enzymatic and cell proliferation-inducing capabilities, that are differentially regulated by phosphorylation and dephosphorylation

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

Henkels, Karen M.; Short, Stephen; Peng, Hong-Juan

2009-11-13

Phospholipase D2 (PLD2) overexpression in mammalian cells results in cell transformation. We have hypothesized that this is due to an increase of de novo DNA synthesis. We show here that overexpression of PLD2-WT leads to an increased DNA synthesis, as measured by the expression levels of the proliferation markers PCNA, p27{sup KIP1} and phospho-histone-3. The enhancing effect was even higher with phosphorylation-deficient PLD2-Y179F and PLD2-Y511F mutants. The mechanism for this did not involve the enzymatic activity of the lipase, but, rather, the presence of the protein tyrosine phosphatase CD45, as silencing with siRNA for CD45 abrogated the effect. The twomore » Y{yields}F mutants had in common a YxN consensus site that, in the phosphorylated counterparts, could be recognized by SH2-bearing proteins, such as Grb2. Even though Y179F and Y511F cannot bind Grb2, they could still find other protein partners, one of which, we have reasoned, could be CD45 itself. Affinity purified PLD2 is indeed activated by Grb2 and deactivated by CD45 in vitro. We concluded that phosphorylated PLD2, aided by Grb2, mediates lipase activity, whereas dephosphorylated PLD2 mediates an induction of cell proliferation, and the specific residues involved in this newly discovered regulation of PLD2 are Y{sup 179} and Y{sup 511}.« less

Adaptive evolution of centromere proteins in plants and animals

PubMed Central

Talbert, Paul B; Bryson, Terri D; Henikoff, Steven

2004-01-01

Background Centromeres represent the last frontiers of plant and animal genomics. Although they perform a conserved function in chromosome segregation, centromeres are typically composed of repetitive satellite sequences that are rapidly evolving. The nucleosomes of centromeres are characterized by a special H3-like histone (CenH3), which evolves rapidly and adaptively in Drosophila and Arabidopsis. Most plant, animal and fungal centromeres also bind a large protein, centromere protein C (CENP-C), that is characterized by a single 24 amino-acid motif (CENPC motif). Results Whereas we find no evidence that mammalian CenH3 (CENP-A) has been evolving adaptively, mammalian CENP-C proteins contain adaptively evolving regions that overlap with regions of DNA-binding activity. In plants we find that CENP-C proteins have complex duplicated regions, with conserved amino and carboxyl termini that are dissimilar in sequence to their counterparts in animals and fungi. Comparisons of Cenpc genes from Arabidopsis species and from grasses revealed multiple regions that are under positive selection, including duplicated exons in some grasses. In contrast to plants and animals, yeast CENP-C (Mif2p) is under negative selection. Conclusions CENP-Cs in all plant and animal lineages examined have regions that are rapidly and adaptively evolving. To explain these remarkable evolutionary features for a single-copy gene that is needed at every mitosis, we propose that CENP-Cs, like some CenH3s, suppress meiotic drive of centromeres during female meiosis. This process can account for the rapid evolution and the complexity of centromeric DNA in plants and animals as compared to fungi. PMID:15345035

GRB 170817A Associated with GW170817: Multi-frequency Observations and Modeling of Prompt Gamma-Ray Emission

NASA Astrophysics Data System (ADS)

Pozanenko, A. S.; Barkov, M. V.; Minaev, P. Yu.; Volnova, A. A.; Mazaeva, E. D.; Moskvitin, A. S.; Krugov, M. A.; Samodurov, V. A.; Loznikov, V. M.; Lyutikov, M.

2018-01-01

We present our observations of electromagnetic transients associated with GW170817/GRB 170817A using optical telescopes of Chilescope observatory and Big Scanning Antenna (BSA) of Pushchino Radio Astronomy Observatory at 110 MHz. The Chilescope observatory detected an optical transient of ∼19m on the third day in the outskirts of the galaxy NGC 4993; we continued observations following its rapid decrease. We put an upper limit of 1.5 × 104 Jy on any radio source with a duration of 10–60 s, which may be associated with GW170817/GRB 170817A. The prompt gamma-ray emission consists of two distinctive components—a hard short pulse delayed by ∼2 s with respect to the LIGO signal and softer thermal pulse with T ∼ 10 keV lasting for another ∼2 s. The appearance of a thermal component at the end of the burst is unusual for short GRBs. Both the hard and the soft components do not satisfy the Amati relation, making GRB 170817A distinctively different from other short GRBs. Based on gamma-ray and optical observations, we develop a model for the prompt high-energy emission associated with GRB 170817A. The merger of two neutron stars creates an accretion torus of ∼10‑2 M ⊙, which supplies the black hole with magnetic flux and confines the Blandford–Znajek-powered jet. We associate the hard prompt spike with the quasispherical breakout of the jet from the disk wind. As the jet plows through the wind with subrelativistic velocity, it creates a radiation-dominated shock that heats the wind material to tens of kiloelectron volts, producing the soft thermal component.

SWIFT OBSERVATIONS OF GAMMA-RAY BURST PULSE SHAPES: GRB PULSE SPECTRAL EVOLUTION CLARIFIED

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

Hakkila, Jon; Lien, Amy; Sakamoto, Takanori

Isolated Swift gamma-ray burst (GRB) pulses, like their higher-energy BATSE counterparts, emit the bulk of their pulsed emission as a hard-to-soft component that can be fitted by the Norris et al. empirical pulse model. This signal is overlaid by a fainter, three-peaked signal that can be modeled by the residual fit of Hakkila and Preece: the two fits combine to reproduce GRB pulses with distinctive three-peaked shapes. The precursor peak appears on or before the pulse rise and is often the hardest component, the central peak is the brightest, and the decay peak converts exponentially decaying emission into a long,more » soft, power-law tail. Accounting for systematic instrumental differences, the general characteristics of the fitted pulses are remarkably similar. Isolated GRB pulses are dominated by hard-to-soft evolution; this is more pronounced for asymmetric pulses than for symmetric ones. Isolated GRB pulses can also exhibit intensity tracking behaviors that, when observed, are tied to the timing of the three peaks: pulses with the largest maximum hardnesses are hardest during the precursor, those with smaller maximum hardnesses are hardest during the central peak, and all pulses can re-harden during the central peak and/or during the decay peak. Since these behaviors are essentially seen in all isolated pulses, the distinction between “hard-to-soft and “intensity-tracking” pulses really no longer applies. Additionally, the triple-peaked nature of isolated GRB pulses seems to indicate that energy is injected on three separate occasions during the pulse duration: theoretical pulse models need to account for this.« less

Mammalian Per-Arnt-Sim proteins in environmental adaptation.

PubMed

McIntosh, Brian E; Hogenesch, John B; Bradfield, Christopher A

2010-01-01

The Per-Arnt-Sim (PAS) domain is conserved across the kingdoms of life and found in an ever-growing list of proteins. This domain can bind to and sense endogenous or xenobiotic small molecules such as molecular oxygen, cellular metabolites, or polyaromatic hydrocarbons. Members of this family are often found in pathways that regulate responses to environmental change; in mammals these include the hypoxia, circadian, and dioxin response pathways. These pathways function in development and throughout life to regulate cellular, organ, and whole-organism adaptive responses. Remarkably, in the case of the clock, this adaptation includes anticipation of environmental change. In this review, we summarize the roles of PAS domain-containing proteins in mammals. We provide structural evidence that functionally classifies both known and unknown biological roles. Finally, we discuss the role of PAS proteins in anticipation of and adaptation to environmental change.

GRB Diversity vs. Utility as Cosmological Probes

NASA Technical Reports Server (NTRS)

Norris, J. P.; Scargle, J. D.; Bonnell, J. T.; Nemiroff, R. J.; Young, Richard E. (Technical Monitor)

1997-01-01

Recent detections of apparent gamma-ray burst (GRB) counterparts in optical and radio wavebands strongly favor the cosmological distance scale, at least for some GRBs, opening the possibility of GRBs serving as cosmological probes. But GRBs exhibit great diversity: in total duration; in number, width and pulse configuration; and in pulse and overall spectral evolution. However, it is possible that a portion of this behavior reflects a luminosity distribution, and possible that evolution of with cosmic time introduces dispersion into the average GRB characteristics -- issues analogous to those encountered with quasars. The temporal domain offers a rich avenue to investigate this problem. When corrected for assumed spectral redshift, time dilation of event durations, pulse widths, and intervals between pulses must yield the same time-dilation factor as a function of peak flux, or else a luminosity distribution may be the cause of observed time dilation effects. We describe results of burst analysis using an automated, Bayesian-based algorithm to determine burst temporal characteristics for different peak flux groups, and derived constraints on any physical process that would introduce a luminosity distribution.

A Unified Model for GRB Prompt Emission from Optical to Gamma-Rays; Exploring GRBs as Standard Candles

NASA Technical Reports Server (NTRS)

Guiriec, S.; Kouveliotou, C.; Hartmann, D. H.; Granot, J.; Asano, K.; Meszaros, P.; Gill, R.; Gehrels, N.; McEnery, J.

2016-01-01

The origin of prompt emission from gamma-ray bursts (GRBs) remains to be an open question. Correlated prompt optical and gamma-ray emission observed in a handful of GRBs strongly suggests a common emission region, but failure to adequately fit the broadband GRB spectrum prompted the hypothesis of different emission mechanisms for the low- and high-energy radiations. We demonstrate that our multi-component model for GRB -ray prompt emission provides an excellent fit to GRB 110205A from optical to gamma-ray energies. Our results show that the optical and highest gamma-ray emissions have the same spatial and spectral origin, which is different from the bulk of the X- and softest gamma-ray radiation. Finally, our accurate redshift estimate for GRB 110205A demonstrates promise for using GRBs as cosmological standard candles.

GRB 091127: The cooling break race on magnetic fuel

NASA Astrophysics Data System (ADS)

Filgas, R.; Greiner, J.; Schady, P.; Krühler, T.; Updike, A. C.; Klose, S.; Nardini, M.; Kann, D. A.; Rossi, A.; Sudilovsky, V.; Afonso, P. M. J.; Clemens, C.; Elliott, J.; Nicuesa Guelbenzu, A.; Olivares E., F.; Rau, A.

2011-11-01

Aims: Using high-quality, broad-band afterglow data for GRB 091127, we investigate the validity of the synchrotron fireball model for gamma-ray bursts (GRBs), and infer physical parameters of the ultra-relativistic outflow. Methods: We used multi-wavelength (NIR to X-ray) follow-up observations obtained with GROND simultaneously in the g'r'i'z'JH filters and the XRT onboard the Swift satellite in the 0.3 to 10 keV energy range. The resulting afterglow light curve is of excellent accuracy with relative photometric errors as low as 1%, and the spectral energy distribution (SED) is well-sampled over 5 decades in energy. These data present one of the most comprehensive observing campaigns for a single GRB afterglow and allow us to test several proposed emission models and outflow characteristics in unprecedented detail. Results: Both the multi-color light curve and the broad-band SED of the afterglow of GRB 091127 show evidence of a cooling break moving from high to lower energies. The early light curve is well described by a broken power-law, where the initial decay in the optical/NIR wavelength range is considerably flatter than at X-rays. Detailed fitting of the time-resolved SED shows that the break is very smooth with a sharpness index of 2.2 ± 0.2, and evolves towards lower frequencies as a power-law with index - 1.23 ± 0.06. These are the first accurate and contemporaneous measurements of both the sharpness of the spectral break and its time evolution. Conclusions: The measured evolution of the cooling break (νc ∝ t~-1.2) is not consistent with the predictions of the standard model, wherein νc ∝ t~-0.5 is expected. A possible explanation for the observed behavior is a time dependence of the microphysical parameters, in particular the fraction of the total energy in the magnetic field ɛB. This conclusion provides further evidence that the standard fireball model is too simplistic, and time-dependent micro-physical parameters may be required to model the

SWIFT Detects a remarkable Gamma-ray Burst, GRB 060514, that introduces a New Classification Scheme

NASA Technical Reports Server (NTRS)

Gehrels, N.; Norris, J. P.; Mangano, V.; Barthelmy, S. D.; Burrows, D. N.; Granot, J.; Kaneko, Y.; Kouveliotou, C.; Markwardt, C. B.; Meszaros, P.;

Photospheric Emission in the Joint GBM and Konus Prompt Spectra of GRB 120323A

NASA Technical Reports Server (NTRS)

Guiriec, S.; Gehrels, N.; McEnery, J.; Kouveliotou, C.; Hartmann, D. H.

2017-01-01

GRB 120323A is a very intense short gamma-ray burst (GRB) detected simultaneously during its prompt gamma-ray emission phase with the Gamma-Ray Burst Monitor (GBM) on board the Fermi Gamma-Ray Space Telescope and the Konus experiment on board the Wind satellite. GBM and Konus operate in the kiloelectronvolt - megaelectronvolt regime; however, the GBM range is broader toward both the low and the high parts of the gamma-ray spectrum. Analyses of such bright events provide a unique opportunity to check the consistency of the data analysis as well as cross-calibrate the two instruments. We performed time-integrated and coarse time-resolved spectral analysis of GRB 120323A prompt emission. We conclude that the analyses of GBM and Konus data are only consistent when using a double-hump spectral shape for both data sets; in contrast, the single hump of the empirical Band function, traditionally used to fit GRB prompt emission spectra, leads to significant discrepancies between GBM and Konus analysis results. Our two-hump model is a combination of a thermal-like and a non-thermal component. We interpret the first component as a natural manifestation of the jet photospheric emission.

The Signature of the Central Engine in the Weakest Relativistic Explosions: GRB 100316D

NASA Astrophysics Data System (ADS)

Margutti, R.; Soderberg, A. M.; Wieringa, M. H.; Edwards, P. G.; Chevalier, R. A.; Morsony, B. J.; Barniol Duran, R.; Sironi, L.; Zauderer, B. A.; Milisavljevic, D.; Kamble, A.; Pian, E.

2013-11-01

We present late-time radio and X-ray observations of the nearby sub-energetic gamma-ray burst (GRB)100316D associated with supernova (SN) 2010bh. Our broad-band analysis constrains the explosion properties of GRB 100316D to be intermediate between highly relativistic, collimated GRBs and the spherical, ordinary hydrogen-stripped SNe. We find that ~1049 erg is coupled to mildly relativistic (Γ = 1.5-2), quasi-spherical ejecta, expanding into a medium previously shaped by the progenitor mass-loss with a rate of \\dot{M}\\, {\\sim }\\, 10^{-5}\\,M_{\\odot }\\,yr^{-1} (for an assumed wind density profile and wind velocity vw = 1000 km s-1). The kinetic energy profile of the ejecta argues for the presence of a central engine and identifies GRB 100316D as one of the weakest central-engine-driven explosions detected to date. Emission from the central engine is responsible for an excess of soft X-ray radiation that dominates over the standard afterglow at late times (t > 10 days). We connect this phenomenology with the birth of the most rapidly rotating magnetars. Alternatively, accretion onto a newly formed black hole might explain the excess of radiation. However, significant departure from the standard fall-back scenario is required.

High-yield cell-free synthesis of human EGFR by IRES-mediated protein translation in a continuous exchange cell-free reaction format

PubMed Central

Quast, Robert B.; Sonnabend, Andrei; Stech, Marlitt; Wüstenhagen, Doreen A.; Kubick, Stefan

2016-01-01

Cell-free protein synthesis systems derived from eukaryotic sources often provide comparatively low amounts of several μg per ml of de novo synthesized membrane protein. In order to overcome this, we herein demonstrate the high-yield cell-free synthesis of the human EGFR in a microsome-containing system derived from cultured Sf21 cells. Yields were increased more than 100-fold to more than 285 μg/ml by combination of IRES-mediated protein translation with a continuous exchange cell-free reaction format that allowed for prolonged reaction lifetimes exceeding 24 hours. In addition, an orthogonal cell-free translation system is presented that enabled the site-directed incorporation of p-Azido-L-phenylalanine by amber suppression. Functionality of cell-free synthesized receptor molecules is demonstrated by investigation of autophosphorylation activity in the absence of ligand and interaction with the cell-free synthesized adapter molecule Grb2. PMID:27456041

GRB 050717: A Long, Short-Lag Burst Observed by Swift and Konus

NASA Technical Reports Server (NTRS)

Krimm, H. A.; Hurkett, C.; Pal'shin, V.; Norris, J. P.; Zhang, B.; Barthelmy, S. D.; Burrows, D. N.; Gehrels, N.; Golenetskii, S.; Osborne, J. P.;

Sulfate production depicts fed-state adaptation to protein restriction in humans.

PubMed

Hamadeh, M J; Schiffrin, A; Hoffer, L J

2001-08-01

One feature of the adaptation to dietary protein restriction is reduced urea production over the hours after consumption of a test meal of fixed composition. This adaptation is impaired in conventionally treated insulin-dependent diabetes mellitus (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol Endocrinol Metab 272: E59--E67, 1997). We have now tested the response to a test meal containing less protein and included as a main outcome variable the production of sulfate, a specific indicator of sulfur amino acid catabolism. Six normal men consumed a mixed test meal containing 0.25 g protein/kg and 10 kcal/kg while adapted to high (1.5 g x kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They followed the identical protocol twice. Six subjects with insulin-dependent diabetes consumed the test meal while adapted to their customary high-protein diet. Adaptation to protein restriction reproducibly reduced 9-h cumulative postmeal urea N and S production by 22--29% and 49--52%, respectively (both P < 0.05). Similar results were obtained for a postmeal collection period of 6 h. The response of the diabetic subjects was normal. We conclude that reductions in postmeal urea and sulfate production after protein restriction are reproducible and are evident using a postmeal collection period as short as 6 h. Sulfate production effectively depicts fed-state adaptation to protein restriction.

GRB 161219B/SN 2016jca: A low-redshift gamma-ray burst supernova powered by radioactive heating

NASA Astrophysics Data System (ADS)

Cano, Z.; Izzo, L.; de Ugarte Postigo, A.; Thöne, C. C.; Krühler, T.; Heintz, K. E.; Malesani, D.; Geier, S.; Fuentes, C.; Chen, T.-W.; Covino, S.; D'Elia, V.; Fynbo, J. P. U.; Goldoni, P.; Gomboc, A.; Hjorth, J.; Jakobsson, P.; Kann, D. A.; Milvang-Jensen, B.; Pugliese, G.; Sánchez-Ramírez, R.; Schulze, S.; Sollerman, J.; Tanvir, N. R.; Wiersema, K.

2017-09-01

Since the first discovery of a broad-lined type Ic supernova (SN) with a long-duration gamma-ray burst (GRB) in 1998, fewer than fifty GRB-supernovae (SNe) have been discovered. The intermediate-luminosity Swift GRB 161219B and its associated supernova SN 2016jca, which occurred at a redshift of z = 0.1475, represents only the seventh GRB-SN to have been discovered within 1 Gpc, and hence provides an excellent opportunity to investigate the observational and physical properties of these very elusive and rare type of SN. As such, we present optical to near-infrared photometry and optical spectroscopy of GRB 161219B and SN 2016jca, spanning the first three months since its discovery. GRB 161219B exploded in the disk of an edge-on spiral galaxy at a projected distance of 3.4 kpc from the galactic centre. GRB 161219B itself is an outlier in the Ep,I - Eγ,iso plane, while SN 2016jca had a rest-frame, peak absolute V-band magnitude of MV = - 19.0 ± 0.1, which it reached after 12.3 ± 0.7 rest-frame days. We find that the bolometric properties of SN 2016jca are inconsistent with being powered solely by a magnetar central engine, and demonstrate that it was likely powered exclusively by energy deposited by the radioactive decay of nickel and cobalt into their daughter products, which were nucleosynthesised when its progenitor underwent core collapse. We find that 0.22 ± 0.08M⊙ of nickel is required to reproducethe peak luminosity of SN 2016jca, and we constrain an ejecta mass of 5.8 ± 0.3M⊙ and a kinetic energy of 5.1 ± 0.8 × 1052 erg. Finally, we report on a chromatic, pre-maximum bump in the g-band light curve, and discuss its possible origin.

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates – A Substudy

PubMed Central

Hursel, Rick; Martens, Eveline A. P.; Gonnissen, Hanne K. J.; Hamer, Henrike M.; Senden, Joan M. G.; van Loon, Luc J. C.; Westerterp-Plantenga, Margriet S.

2015-01-01

Background Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. Objective To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. Methods A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. Results After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low

Mutational analysis of the SRC homology 2 domain protein-tyrosine phosphatase Corkscrew.

PubMed

Allard, J D; Herbst, R; Carroll, P M; Simon, M A

1998-05-22

The SRC homology 2 (SH2) domain protein-tyrosine phosphatase, Corkscrew (CSW) is required for signaling by receptor tyrosine kinases, including the Sevenless receptor tyrosine kinase (SEV), which directs Drosophila R7 photoreceptor cell development. To investigate the role of the different domains of CSW, we constructed domain-specific csw mutations and assayed their effects on CSW function. Our results indicate that CSW SH2 domain function is essential, but either CSW SH2 domain can fulfill this requirement. We also found that CSW and activated SEV are associated in vivo in a manner that does not require either CSW SH2 domain function or tyrosine phosphorylation of SEV. In contrast, the interaction between CSW and Daughter of Sevenless, a CSW substrate, is dependent on SH2 domain function. These results suggest that the role of the CSW SH2 domains during SEV signaling is to bind Daughter of Sevenless rather than activated SEV. We also found that although CSW protein-tyrosine phosphatase activity is required for full CSW function, a catalytically inactive CSW is capable of providing partial function. In addition, we found that deletion of either the CSW protein- tyrosine phosphatase insert or the entire CSW carboxyl terminus, which includes a conserved DRK/GRB2 SH2 domain binding sequence, does not abolish CSW function.

How protein materials balance strength, robustness, and adaptability

PubMed Central

Buehler, Markus J.; Yung, Yu Ching

2010-01-01

Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro. We focus on alpha-helix based intermediate filament proteins as a model system to explain why the utilization of hierarchical structural features is vital to their ability to combine strength, robustness, and adaptability. Experimental studies demonstrating the activation of angiogenesis, the growth of new blood vessels, are presented as an example of how adaptability of structure in biological tissue is achieved through changes in gene expression that result in an altered material structure. We analyze the concepts in light of the universality and diversity of the structural makeup of protein materials and discuss the findings in the context of potential fundamental evolutionary principles that control their nanoscale structure. We conclude with a discussion of multiscale science in biology and de novo materials design. PMID:20676305

GRB110721A: An extreme peak energy and signatures of the photosphere

DOE PAGES

Axelsson, M.; Baldini, L.; Barbiellini, G.; ...

2012-09-17

GRB110721A was observed by the Fermi Gamma-ray Space Telescope using its two instruments, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). This burst consisted of one major emission episode which lasted for ~24.5 s (in the GBM) and had a peak flux of (5.7 ± 0.2) × 10 –5 erg s –1 cm –2. The time-resolved emission spectrum is best modeled with a combination of a Band function and a blackbody spectrum. The peak energy of the Band component was initially 15 ± 2 MeV, which is the highest value ever detected in a GRB. We mademore » this measurement by combining GBM/BGO data with LAT Low Energy events to achieve continuous 10-100 MeV coverage. The peak energy later decreased as a power law in time with an index of –1.89 ± 0.10. The temperature of the blackbody component also decreased, starting from ~80 keV, and the decay showed a significant break after ~2 s. The spectrum provides strong constraints on the standard synchrotron model, indicating that alternative mechanisms may give rise to the emission at these energies.« less

The high-redshift gamma-ray burst GRB 140515A. A comprehensive X-ray and optical study

NASA Astrophysics Data System (ADS)

Melandri, A.; Bernardini, M. G.; D'Avanzo, P.; Sánchez-Ramírez, R.; Nappo, F.; Nava, L.; Japelj, J.; de Ugarte Postigo, A.; Oates, S.; Campana, S.; Covino, S.; D'Elia, V.; Ghirlanda, G.; Gafton, E.; Ghisellini, G.; Gnedin, N.; Goldoni, P.; Gorosabel, J.; Libbrecht, T.; Malesani, D.; Salvaterra, R.; Thöne, C. C.; Vergani, S. D.; Xu, D.; Tagliaferri, G.

2015-09-01

High-redshift gamma-ray bursts (GRBs) offer several advantages when studying the distant Universe, providing unique information about the structure and properties of the galaxies in which they exploded. Spectroscopic identification with large ground-based telescopes has improved our knowledge of this kind of distant events. We present the multi-wavelength analysis of the high-zSwift GRB GRB 140515A (z = 6.327). The best estimate of the neutral hydrogen fraction of the intergalactic medium towards the burst is xHI ≤ 0.002. The spectral absorption lines detected for this event are the weakest lines ever observed in GRB afterglows, suggesting that GRB 140515A exploded in a very low-density environment. Its circum-burst medium is characterised by an average extinction (AV ~ 0.1) that seems to be typical of z ≥ 6 events. The observed multi-band light curves are explained either with a very hard injected spectrum (p = 1.7) or with a multi-component emission (p = 2.1). In the second case a long-lasting central engine activity is needed in order to explain the late time X-ray emission. The possible origin of GRB 140515A in a Pop III (or in a Pop II star with a local environment enriched by Pop III) massive star is unlikely. Based on observations collected at the European Southern Observatory, ESO, the VLT/Kueyen telescope, Paranal, Chile (proposal code: 093.A-0069), on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofísica de Canarias (programme 49-008), and on observations made with the Italian 3.6-m Telescopio Nazionale Galileo (TNG), operated by the Fundación Galileo Galilei of the INAF (Instituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofísica de Canarias (programme A26TAC_63).Appendix A is available in electronic form at

Photospheric Emission in the Joint GBM and Konus Prompt Spectra of GRB 120323A

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

Guiriec, S.; Kouveliotou, C.; Gehrels, N.

GRB 120323A is a very intense short gamma -ray burst (GRB) detected simultaneously during its prompt γ -ray emission phase with the Gamma-ray Burst Monitor (GBM) on board the Fermi Gamma-ray Space Telescope and the Konus experiment on board the Wind satellite. GBM and Konus operate in the keV–MeV regime; however, the GBM range is broader toward both the low and the high parts of the γ -ray spectrum. Analyses of such bright events provide a unique opportunity to check the consistency of the data analysis as well as cross-calibrate the two instruments. We performed time-integrated and coarse time-resolved spectralmore » analysis of GRB 120323A prompt emission. We conclude that the analyses of GBM and Konus data are only consistent when using a double-hump spectral shape for both data sets; in contrast, the single hump of the empirical Band function, traditionally used to fit GRB prompt emission spectra, leads to significant discrepancies between GBM and Konus analysis results. Our two-hump model is a combination of a thermal-like and a non-thermal component. We interpret the first component as a natural manifestation of the jet photospheric emission.« less

Behind the dust curtain: the spectacular case of GRB 160623A

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

Pintore, F.; Tiengo, A.; Mereghetti, S.

Here, we report on the X-ray dust-scattering features observed around the afterglow of the gamma-ray burst GRB 160623A. With an XMM–Newton observation carried out ~2 d after the burst, we found evidence of at least six rings, with angular size expanding between ~2 and 9 arcmin, as expected for X-ray scattering of the prompt gamma-ray burst (GRB) emission by dust clouds in our Galaxy. From the expansion rate of the rings, we measured the distances of the dust layers with extraordinary precision: 528.1 ± 1.2, 679.2 ± 1.9, 789.0 ± 2.8, 952 ± 5, 1539 ± 20 and 5079 ±more » 64 pc. A spectral analysis of the ring spectra, based on an appropriate dust-scattering model (BARE-GR-B) and the estimated burst fluence, allowed us to derive the column density of the individual dust layers, which are in the range 7 × 10 20–1.5 × 10 22 cm –2. The farthest dust layer (i.e. the one responsible for the smallest ring) is also the one with the lowest column density and it is possibly very extended, indicating a diffuse dust region. The properties derived for the six dust layers (distance, thickness and optical depth) are generally in good agreement with independent information on the reddening along this line of sight and on the distribution of molecular and atomic gas.« less

Behind the dust curtain: the spectacular case of GRB 160623A

DOE PAGES

Pintore, F.; Tiengo, A.; Mereghetti, S.; ...

2017-08-14

Here, we report on the X-ray dust-scattering features observed around the afterglow of the gamma-ray burst GRB 160623A. With an XMM–Newton observation carried out ~2 d after the burst, we found evidence of at least six rings, with angular size expanding between ~2 and 9 arcmin, as expected for X-ray scattering of the prompt gamma-ray burst (GRB) emission by dust clouds in our Galaxy. From the expansion rate of the rings, we measured the distances of the dust layers with extraordinary precision: 528.1 ± 1.2, 679.2 ± 1.9, 789.0 ± 2.8, 952 ± 5, 1539 ± 20 and 5079 ±more » 64 pc. A spectral analysis of the ring spectra, based on an appropriate dust-scattering model (BARE-GR-B) and the estimated burst fluence, allowed us to derive the column density of the individual dust layers, which are in the range 7 × 10 20–1.5 × 10 22 cm –2. The farthest dust layer (i.e. the one responsible for the smallest ring) is also the one with the lowest column density and it is possibly very extended, indicating a diffuse dust region. The properties derived for the six dust layers (distance, thickness and optical depth) are generally in good agreement with independent information on the reddening along this line of sight and on the distribution of molecular and atomic gas.« less

Behind the dust curtain: the spectacular case of GRB 160623A

NASA Astrophysics Data System (ADS)

Pintore, F.; Tiengo, A.; Mereghetti, S.; Vianello, G.; Salvaterra, R.; Esposito, P.; Costantini, E.; Giuliani, A.; Bosnjak, Z.

2017-12-01

We report on the X-ray dust-scattering features observed around the afterglow of the gamma-ray burst GRB 160623A. With an XMM-Newton observation carried out ∼2 d after the burst, we found evidence of at least six rings, with angular size expanding between ∼2 and 9 arcmin, as expected for X-ray scattering of the prompt gamma-ray burst (GRB) emission by dust clouds in our Galaxy. From the expansion rate of the rings, we measured the distances of the dust layers with extraordinary precision: 528.1 ± 1.2, 679.2 ± 1.9, 789.0 ± 2.8, 952 ± 5, 1539 ± 20 and 5079 ± 64 pc. A spectral analysis of the ring spectra, based on an appropriate dust-scattering model (BARE-GR-B) and the estimated burst fluence, allowed us to derive the column density of the individual dust layers, which are in the range 7 × 1020-1.5 × 1022 cm-2. The farthest dust layer (i.e. the one responsible for the smallest ring) is also the one with the lowest column density and it is possibly very extended, indicating a diffuse dust region. The properties derived for the six dust layers (distance, thickness and optical depth) are generally in good agreement with independent information on the reddening along this line of sight and on the distribution of molecular and atomic gas.

Circular polarization in the optical afterglow of GRB 121024A.

PubMed

Wiersema, K; Covino, S; Toma, K; van der Horst, A J; Varela, K; Min, M; Greiner, J; Starling, R L C; Tanvir, N R; Wijers, R A M J; Campana, S; Curran, P A; Fan, Y; Fynbo, J P U; Gorosabel, J; Gomboc, A; Götz, D; Hjorth, J; Jin, Z P; Kobayashi, S; Kouveliotou, C; Mundell, C; O'Brien, P T; Pian, E; Rowlinson, A; Russell, D M; Salvaterra, R; di Serego Alighieri, S; Tagliaferri, G; Vergani, S D; Elliott, J; Fariña, C; Hartoog, O E; Karjalainen, R; Klose, S; Knust, F; Levan, A J; Schady, P; Sudilovsky, V; Willingale, R

2014-05-08

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

GRB070125: The First Long-Duration Gamma-Ray Burst in a Halo Environment

NASA Technical Reports Server (NTRS)

Bradley, Cenko S.; Fox, Derek B.; Penprase, Brian E.; Kulkarni, Shri R.; Price, Paul A.; Berger, Edo; Kulkarni, Shri R.; Harrison, Fiona A.; Gal-Yam, Avishay; Ofek, Eran O.;

Observation of X-ray lines from a gamma-ray burst (GRB991216): evidence of moving ejecta from the progenitor.

PubMed

Piro, L; Garmire, G; Garcia, M; Stratta, G; Costa, E; Feroci, M; Mészáros, P; Vietri, M; Bradt, H; Frail, D; Frontera, F; Halpern, J; Heise, J; Hurley, K; Kawai, N; Kippen, R M; Marshall, F; Murakami, T; Sokolov, V V; Takeshima, T; Yoshida, A

2000-11-03

We report on the discovery of two emission features observed in the x-ray spectrum of the afterglow of the gamma-ray burst (GRB) of 16 December 1999 by the Chandra X-ray Observatory. These features are identified with the Ly(alpha) line and the narrow recombination continuum by hydrogenic ions of iron at a redshift z = 1.00 +/- 0.02, providing an unambiguous measurement of the distance of a GRB. Line width and intensity imply that the progenitor of the GRB was a massive star system that ejected, before the GRB event, a quantity of iron approximately 0.01 of the mass of the sun at a velocity approximately 0.1 of the speed of light, probably by a supernova explosion.

RAPTOR: Closed-Loop monitoring of the night sky and the earliest optical detection of GRB 021211

NASA Astrophysics Data System (ADS)

Vestrand, W. T.; Borozdin, K.; Casperson, D. J.; Fenimore, E.; Galassi, M.; McGowan, K.; Starr, D.; White, R. R.; Wozniak, P.; Wren, J.

2004-10-01

We discuss the RAPTOR (Rapid Telescopes for Optical Response) sky monitoring system at Los Alamos National Laboratory. RAPTOR is a fully autonomous robotic system that is designed to identify and make follow-up observations of optical transients with durations as short as one minute. The RAPTOR design is based on Biomimicry of Human Vision. The sky monitor is composed of two identical arrays of telescopes, separated by 38 kilometers, which stereoscopically monitor a field of about 1300 square-degrees for transients. Both monitoring arrays are carried on rapidly slewing mounts and are composed of an ensemble of wide-field telescopes clustered around a more powerful narrow-field telescope called the ``fovea'' telescope. All telescopes are coupled to real-time analysis pipelines that identify candidate transients and relay the information to a central decision unit that filters the candidates to find real celestial transients and command a response. When a celestial transient is found, the system can point the fovea telescopes to any position on the sky within five seconds and begin follow-up observations. RAPTOR also responds to Gamma Ray Burst (GRB) alerts generated by GRB monitoring spacecraft. Here we present RAPTOR observations of GRB 021211 that constitute the earliest detection of optical emission from that event and are the second fastest achieved for any GRB. The detection of bright optical emission from GRB021211, a burst with modest gamma-ray fluence, indicates that prompt optical emission, detectable with small robotic telescopes, is more common than previously thought. Further, the very fast decline of the optical afterglow from GRB 021211 suggests that some so-called ``optically dark'' GRBs were not detected only because of the slow response of the follow-up telescopes.

SN 2013dx associated with GRB 130702A: a detailed photometric and spectroscopic monitoring and a study of the environment

NASA Astrophysics Data System (ADS)

D'Elia, Valerio

2015-08-01

Long duration gamma-ray bursts (GRBs) and broad-line, type Ic supernovae (SNe) are strongly connected. We aim at characterizing SN 2013dx, associated with GRB 130702A, through sensitive and extensive ground-based observational campaigns in the optical-IR band.We monitored the field of the Swift GRB 130702A (redshift z = 0.145) using the 8.2-m VLT, the 3.6-m TNG and the 0.6-m REM telescopes during the time interval between 4 and 40 days after the burst. Photometric and spectroscopic observations revealed the presence of the associated Type Ic SN 2013dx. Our multi-band photometry allowed the construction of a bolometric light curve.The bolometric light curve of SN 2013dx resembles that of 2003dh (associated with GRB 030329), but is ~ 10% faster and ~25% dimmer. From this we infer a synthesized 56Ni mass of ~0.3 solar masses. The multi-epoch optical spectroscopy shows that the SN 2013dx behavior is best matched by SN 1998bw, among the other well-known low-z SNe associated with GRBs and XRFs, and by SN 2010ah, an energetic Type Ic SN not associated with any GRB. The photospheric velocity of the ejected material declines from ~ 2.7 X10^4 km/s at 8 rest frame days from the explosion, to ~3.5X103 km/s at 40 days. These values are extremely close to those of SN1998bw and 2010ah. We deduce for SN 2013dx a kinetic energy of (32 +/- 9)X10^51 erg, and an ejected mass of 7 +/- 1 solar masses. This suggests that the progenitor of SN2013dx had a mass of ~25 solar masses, i.e., 15-20% less massive than that of SN 1998bw.Finally, we perfom a study of the SN 2013dx environment, through spectroscopy of the closeby galaxies. 9 out of the 14 inspected galaxies lie within 0.03 in redshift from z=0.145, indicating that the host of GRB 130702A/SN 2013dx belongs to a group of galaxies, an unprecedented finding for a GRB-associated SN and, to our knowledge, for long GRBs in general.

Prospects for GRB science with the Fermi Large Area Telescope

DOE PAGES

Band, D. L.; Axelsson, M.; Baldini, L.; ...

2009-08-04

The Large Area Telescope (LAT) instrument on the Fermi mission will reveal the rich spectral and temporal gamma-ray burst (GRB) phenomena in the >100 MeV band. The synergy with Fermi's Gamma-ray Burst Monitor detectors will link these observations to those in the well explored 10-1000 keV range; the addition of the >100 MeV band observations will resolve theoretical uncertainties about burst emission in both the prompt and afterglow phases. Trigger algorithms will be applied to the LAT data both onboard the spacecraft and on the ground. Furthermore, the sensitivity of these triggers will differ because of the available computing resourcesmore » onboard and on the ground. Here we present the LAT's burst detection methodologies and the instrument's GRB capabilities.« less

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

NASA Astrophysics Data System (ADS)

Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

2016-02-01

Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

Adaptation in protein fitness landscapes is facilitated by indirect paths

PubMed Central

Wu, Nicholas C; Dai, Lei; Olson, C Anders; Lloyd-Smith, James O; Sun, Ren

2016-01-01

The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20L) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 204 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. DOI: http://dx.doi.org/10.7554/eLife.16965.001 PMID:27391790

The GW170817/GRB 170817A/AT 2017gfo Association: Some Implications for Physics and Astrophysics

NASA Astrophysics Data System (ADS)

Wang, Hao; Zhang, Fu-Wen; Wang, Yuan-Zhu; Shen, Zhao-Qiang; Liang, Yun-Feng; Li, Xiang; Liao, Neng-Hui; Jin, Zhi-Ping; Yuan, Qiang; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

2017-12-01

On 2017 August 17, a gravitational-wave event (GW170817) and an associated short gamma-ray burst (GRB 170817A) from a binary neutron star merger had been detected. The follow-up optical/infrared observations also identified the macronova/kilonova emission (AT 2017gfo). In this work, we discuss some implications of the remarkable GW170817/GRB 170817A/AT 2017gfo association. We show that the ∼1.7 s time delay between the gravitational-wave (GW) and GRB signals imposes very tight constraints on the superluminal movement of gravitational waves (i.e., the relative departure of GW velocity from the speed of light is ≤slant 4.3× {10}-16) or the possible violation of the weak equivalence principle (i.e., the difference of the gamma-ray and GW trajectories in the gravitational field of the galaxy and the local universe should be within a factor of ∼ 3.4× {10}-9). The so-called Dark Matter Emulators and a class of contender models for cosmic acceleration (“Covariant Galileon”) are ruled out as well. The successful identification of lanthanide elements in the macronova/kilonova spectrum also excludes the possibility that the progenitors of GRB 170817A are a binary strange star system. The high neutron star merger rate (inferred from both the local sGRB data and the gravitational-wave data) together with the significant ejected mass strongly suggest that such mergers are the prime sites of heavy r-process nucleosynthesis.

Prompt gamma-ray emission of GRB 170817A associated to GW 170817: A consistent picture

NASA Astrophysics Data System (ADS)

Ziaeepour, Houri

2018-05-01

The short GRB 170817A associated to the first detection of gravitation waves from a Binary Neutron Star (BNS) merger was in many ways unusual. Possible explanations are emission from a cocoon or cocoon break out, off-axis view of a structured or uniform jet, and on-axis ultra-relativistic jet with reduced density and Lorentz factor. Here we use a phenomenological model of shock evolution and synchrotron/self-Compton emission to simulate the prompt emission of GRB 170817A and to test above proposals. We find that synchrotron emission from a mildly relativistic cocoon with a Lorentz factor of 2-3, as considered in the literature, generates a too soft, too long, and too bright prompt emission. Off-axis view of an structured jet with a Lorentz factor of about 10 can reproduce observations, but needs a very efficient transfer of kinetic energy to electrons in internal shocks, which is disfavored by particle in cell simulations. We also comment on cocoon breakout as a mechanism for generation of the prompt gamma-ray. A relativistic jet with a Lorentz factor of about 100 and a density lower than typical short GRBs seems to be the most plausible model and we conclude that GRB 170817A was intrinsically faint. Based on this result and findings of relativistic magnetohydrodynamics simulations of BNS merger in the literature we discuss physical and astronomical conditions, which may lead to such faint short GRBs. We identify small mass difference of progenitor neutron stars, their old age and reduced magnetic field, and anti-alignment of spin-orbit angular momentum induced by environmental gravitational disturbances during the lifetime of the BNS as causes for the faintness of GRB 170817A. We predict that BNS mergers at lower redshifts generate on average fainter GRBs.

Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation.

PubMed

Fragale, Alessandra; Tartaglia, Marco; Wu, Jie; Gelb, Bruce D

2004-03-01

Noonan syndrome is a developmental disorder with dysmorphic facies, short stature, cardiac defects, and skeletal anomalies, which can be caused by missense PTPN11 mutations. PTPN11 encodes Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2 or SHP-2), a protein tyrosine phosphatase that acts in signal transduction downstream to growth factor, hormone, and cytokine receptors. We compared the functional effects of three Noonan syndrome-causative PTPN11 mutations on SHP2's phosphatase activity, interaction with a binding partner, and signal transduction. All SHP2 mutants had significantly increased basal phosphatase activity compared to wild type, but that activity varied significantly between mutants and was further increased after epidermal growth factor stimulation. Cells expressing SHP2 mutants had prolonged extracellular signal-regulated kinase 2 activation, which was ligand-dependent. Binding of SHP2 mutants to Grb2-associated binder-1 was increased and sustained, and tyrosine phosphorylation of both proteins was prolonged. Coexpression of Grb2-associated binder-1-FF, which lacks SHP2 binding motifs, blocked the epidermal growth factor-mediated increase in SHP2's phosphatase activity and resulted in a dramatic reduction of extracellular signal-regulated kinase 2 activation. Taken together, these results document that Noonan syndrome-associated PTPN11 mutations increase SHP2's basal phosphatase activity, with greater activation when residues directly involved in binding at the interface between the N-terminal Src homology 2 and protein tyrosine phosphatase domains are altered. The SHP2 mutants prolonged signal flux through the RAS/mitogen-activated protein kinase (ERK2/MAPK1) pathway in a ligand-dependent manner that required docking through Grb2-associated binder-1 (GAB1), leading to increased cell proliferation. Copyright 2004 Wiley-Liss, Inc.

Co-evolution of proteins and solutions: protein adaptation versus cytoprotective micromolecules and their roles in marine organisms.

PubMed

Yancey, Paul H; Siebenaller, Joseph F

2015-06-01

Organisms experience a wide range of environmental factors such as temperature, salinity and hydrostatic pressure, which pose challenges to biochemical processes. Studies on adaptations to such factors have largely focused on macromolecules, especially intrinsic adaptations in protein structure and function. However, micromolecular cosolutes can act as cytoprotectants in the cellular milieu to affect biochemical function and they are now recognized as important extrinsic adaptations. These solutes, both inorganic and organic, have been best characterized as osmolytes, which accumulate to reduce osmotic water loss. Singly, and in combination, many cosolutes have properties beyond simple osmotic effects, e.g. altering the stability and function of proteins in the face of numerous stressors. A key example is the marine osmolyte trimethylamine oxide (TMAO), which appears to enhance water structure and is excluded from peptide backbones, favoring protein folding and stability and counteracting destabilizers like urea and temperature. Co-evolution of intrinsic and extrinsic adaptations is illustrated with high hydrostatic pressure in deep-living organisms. Cytosolic and membrane proteins and G-protein-coupled signal transduction in fishes under pressure show inhibited function and stability, while revealing a number of intrinsic adaptations in deep species. Yet, intrinsic adaptations are often incomplete, and those fishes accumulate TMAO linearly with depth, suggesting a role for TMAO as an extrinsic 'piezolyte' or pressure cosolute. Indeed, TMAO is able to counteract the inhibitory effects of pressure on the stability and function of many proteins. Other cosolutes are cytoprotective in other ways, such as via antioxidation. Such observations highlight the importance of considering the cellular milieu in biochemical and cellular adaptation. © 2015. Published by The Company of Biologists Ltd.

GRB 080319B: A Naked-Eye Stellar Blast from the Distant Universe

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

Racusin, J. L.; Burrows, D. N.

On behalf of a large international collaboration [1], we present the unprecedented broadband observations of GRB 080319B, whose prompt optical emission peaked at a visual magnitude of 5.3, making it briefly visible with the naked eye. GRB 080319B was discovered by Swift and captured in exquisite detail by ground based wide-field telescopes, imaging the burst location from before the time of the explosion. The combination of these unique optical data with simultaneous {gamma}-ray observations provides powerful diagnostics of the detailed physics of this explosion within seconds of its formation. We show that the prompt optical and {gamma}-ray emissions from thismore » event arise from different spectral components within the same physical region located at a large distance from the source, implying an extremely relativistic outflow. Our observations also provide good evidence for a bright reverse shock component. The chromatic behavior of the broadband afterglow is consistent with viewing the GRB down the very narrow inner core of a two-component jet that is expanding into a wind-like environment consistent with the massive star origin of long GRBs.« less

Tubby family proteins are adapters for ciliary trafficking of integral membrane proteins

PubMed Central

Shimada, Issei S.; Loriot, Evan

2017-01-01

The primary cilium is a paradigmatic organelle for studying compartmentalized signaling; however, unlike soluble protein trafficking, processes targeting integral membrane proteins to cilia are poorly understood. In this study, we determine that the tubby family protein TULP3 functions as a general adapter for ciliary trafficking of structurally diverse integral membrane cargo, including multiple reported and novel rhodopsin family G protein–coupled receptors (GPCRs) and the polycystic kidney disease–causing polycystin 1/2 complex. The founding tubby family member TUB also localizes to cilia similar to TULP3 and determines trafficking of a subset of these GPCRs to neuronal cilia. Using minimal ciliary localization sequences from GPCRs and fibrocystin (also implicated in polycystic kidney disease), we demonstrate these motifs to be sufficient and TULP3 dependent for ciliary trafficking. We propose a three-step model for TULP3/TUB-mediated ciliary trafficking, including the capture of diverse membrane cargo by the tubby domain in a phosphoinositide 4,5-bisphosphate (PI(4,5)P2)-dependent manner, ciliary delivery by intraflagellar transport complex A binding to the TULP3/TUB N terminus, and subsequent release into PI(4,5)P2-deficient ciliary membrane. PMID:28154160

On the Neutrino Non-detection of GRB 130427A

NASA Astrophysics Data System (ADS)

Gao, Shan; Kashiyama, Kazumi; Mészáros, Peter

2013-07-01

The recent gamma-ray burst GRB 130427A has an isotropic electromagnetic energy E iso ~ 1054 erg, suggesting an ample supply of target photons for photo-hadronic interactions, which at its low redshift of z ~ 0.34 would appear to make it a promising candidate for neutrino detection. However, the IceCube collaboration has reported a null result based on a search during the prompt emission phase. We show that this neutrino non-detection can provide valuable information about this gamma-ray burst's (GRB's) key physical parameters such as the emission radius Rd , the bulk Lorentz factor Γ, and the energy fraction converted into cosmic rays epsilon p . The results are discussed both in a model-independent way and in the specific scenarios of an internal shock (IS) model, a baryonic photospheric (BPH) model, and a magnetic photospheric (MPH) model. We find that the constraints are most stringent for the MPH model considered, but the constraints on the IS and the BPH models are fairly modest.

VizieR Online Data Catalog: Fermi/GBM GRB time-resolved spectral catalog (Yu+, 2016)

NASA Astrophysics Data System (ADS)

Yu, H.-F.; Preece, R. D.; Greiner, J.; Bhat, P. N.; Bissaldi, E.; Briggs, M. S.; Cleveland, W. H.; Connaughton, V.; Goldstein, A.; von Kienlin; A.; Kouveliotou, C.; Mailyan, B.; Meegan, C. A.; Paciesas, W. S.; Rau, A.; Roberts, O. J.; Veres, P.; Wilson-Hodge, C.; Zhang, B.-B.; van Eerten, H. J.

2016-01-01

Time-resolved spectral analysis results of BEST models: for each spectrum GRB name using the Fermi GBM trigger designation, spectrum number within individual burst, start time Tstart and end time Tstop for the time bin, BEST model, best-fit parameters of the BEST model, value of CSTAT per degrees of freedom, 10keV-1MeV photon and energy flux are given. Ep evolutionary trends: for each burst GRB name, number of spectra with Ep, Spearman's Rank Correlation Coefficients between Ep_ and photon flux and 90%, 95%, and 99% confidence intervals, Spearman's Rank Correlation Coefficients between Ep and energy flux and 90%, 95%, and 99% confidence intervals, Spearman's Rank Correlation Coefficient between Ep and time and 90%, 95%, and 99% confidence intervals, trends as determined by computer for 90%, 95%, and 99% confidence intervals, trends as determined by human eyes are given. (2 data files).

GRB 980425 host: [C II], [O I], and CO lines reveal recent enhancement of star formation due to atomic gas inflow

NASA Astrophysics Data System (ADS)

Michałowski, M. J.; Castro Cerón, J. M.; Wardlow, J. L.; Karska, A.; Messias, H.; van der Werf, P.; Hunt, L. K.; Baes, M.; Castro-Tirado, A. J.; Gentile, G.; Hjorth, J.; Le Floc'h, E.; Pérez-Martínez, R.; Nicuesa Guelbenzu, A.; Rasmussen, J.; Rizzo, J. R.; Rossi, A.; Sánchez-Portal, M.; Schady, P.; Sollerman, J.; Xu, D.

2016-11-01

Context. Accretion of gas from the intergalactic medium is required to fuel star formation in galaxies. We have recently suggested that this process can be studied using host galaxies of gamma-ray bursts (GRBs). Aims: Our aim is to test this possibility by studying in detail the properties of gas in the closest galaxy hosting a GRB (980425). Methods: We obtained the first ever far-infrared (FIR) line observations of a GRB host, namely Herschel/PACS resolved [C II] 158 μm and [O I] 63 μm spectroscopy, and an APEX/SHeFI CO(2-1) line detection and ALMA CO(1-0) observations of the GRB 980425 host. Results: The GRB 980425 host has elevated [C II]/FIR and [O I]/FIR ratios and higher values of star formation rates (SFR) derived from line ([C II], [O I], Hα) than from continuum (UV, IR, radio) indicators. [C II] emission exhibits a normal morphology, peaking at the galaxy centre, whereas [O I] is concentrated close to the GRB position and the nearby Wolf-Rayet region. The high [O I] flux indicates that there is high radiation field and high gas density at these positions, as derived from modelling of photo-dissociation regions. The [C II]/CO luminosity ratio of the GRB 980425 host is close to the highest values found for local star-forming galaxies. Indeed, its CO-derived molecular gas mass is low given its SFR and metallicity, but the [C II]-derived molecular gas mass is close to the expected value. Conclusions: The [O I] and H I concentrations and the high radiation field and density close to the GRB position are consistent with the hypothesis of a very recent (at most a few tens of Myr ago) inflow of atomic gas triggering star formation. In this scenario dust has not had time to build up (explaining high line-to-continuum ratios). Such a recent enhancement of star formation activity would indeed manifest itself in high SFRline/SFRcontinuum ratios because the line indicators are sensitive only to recent (≲10 Myr) activity, whereas the continuum indicators measure

THE SWIFT GRB HOST GALAXY LEGACY SURVEY. II. REST-FRAME NEAR-IR LUMINOSITY DISTRIBUTION AND EVIDENCE FOR A NEAR-SOLAR METALLICITY THRESHOLD

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

Perley, D. A.; Tanvir, N. R.; Hjorth, J.

2016-01-20

We present rest-frame near-IR (NIR) luminosities and stellar masses for a large and uniformly selected population of gamma-ray burst (GRB) host galaxies using deep Spitzer Space Telescope imaging of 119 targets from the Swift GRB Host Galaxy Legacy Survey spanning 0.03 < z < 6.3, and we determine the effects of galaxy evolution and chemical enrichment on the mass distribution of the GRB host population across cosmic history. We find a rapid increase in the characteristic NIR host luminosity between z ∼ 0.5 and z ∼ 1.5, but little variation between z ∼ 1.5 and z ∼ 5. Dust-obscured GRBs dominate the massive host population but are only rarely seen associated withmore » low-mass hosts, indicating that massive star-forming galaxies are universally and (to some extent) homogeneously dusty at high redshift while low-mass star-forming galaxies retain little dust in their interstellar medium. Comparing our luminosity distributions with field surveys and measurements of the high-z mass–metallicity relation, our results have good consistency with a model in which the GRB rate per unit star formation is constant in galaxies with gas-phase metallicity below approximately the solar value but heavily suppressed in more metal-rich environments. This model also naturally explains the previously reported “excess” in the GRB rate beyond z ≳ 2; metals stifle GRB production in most galaxies at z < 1.5 but have only minor impact at higher redshifts. The metallicity threshold we infer is much higher than predicted by single-star models and favors a binary progenitor. Our observations also constrain the fraction of cosmic star formation in low-mass galaxies undetectable to Spitzer to be small at z < 4.« less

Concluding Remarks: The Current Status and Future Prospects for GRB Astronomy

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2009-01-01

We are in a remarkable period of discovery in GRB astronomy. The current satellites including Swift, Fermi. AGILE and INTEGRAL are detecting and observing bursts of all varieties. Increasing capabilities for follow-up observations on the ground and in space are leading to rapid and deep coverage across the electromagnetic spectrum, The future will see continued operation of the current experiments and with future missions like SVOM plus possible rni_Ssions like JANUS and EXIST. An exciting expansion of capabilities is occurring in areas of gravitational waves and neutrinos that could open new windows on the GRB phenomenon. Increased IR capabilities on the ground and with missions like JWST will enable further exploration of high redshift bursts. The future is bright.

The Nature of the Remarkable Transient GRB 110328A

NASA Astrophysics Data System (ADS)

Fruchter, Andrew

2010-09-01

One orbit was approved for GO/DD 12447. The PI was given permission to use time under his related approved GRB program, 12370, for subsequent observations of this GRB. To allow the second visit to go forward quickly, it was kept on the schedule as GO/DD 12447, but the orbit was charged to GO 12370. As a result, THE SECOND VISIT OF 12447 HAS THE PROPRIETARY PERIOD ASSOCIATED WITH 12370. We apologize for the confusion caused by this change. However, it was done to allow rapid observations of an unusual astrophysical object.We propose HST observations of the extraordinary transient, GRB 110328A. This object triggered the Swift automatic burst detection twice over the course of about ninety minutes, and has continued to be a bright X-ray source for the two days since. While this behavior might typically suggest a Galactic source, the high Galactic latitude of the object, and its coincidence with a star-forming galaxy at z=0.35 instead suggests a new type of extragalactic transient. WFC3 imaging in the optical and NIR will allow us to search for a varying point source to far greater depth than could be done from the ground, given the presence of an apparent host, and the use of the F160W filter may allow us to pierce enshrouding dust, if extinction is the reason for the present lack of a detection in the optical. While we do not yet know the astrophysical source of this transient, it appears unique among the hundreds of transients so far detected by Swift. This alone should provide strong grounds for HST observations of this unusual and potentially important object.

Anti-apoptotic Role of Caspase-cleaved GAB1 Adaptor Protein in Hepatocyte Growth Factor/Scatter Factor-MET Receptor Protein Signaling*

PubMed Central

Le Goff, Arnaud; Ji, Zongling; Leclercq, Bérénice; Bourette, Roland P.; Mougel, Alexandra; Guerardel, Cateline; de Launoit, Yvan; Vicogne, Jérôme; Goormachtigh, Gautier; Fafeur, Véronique

2012-01-01

The GRB2-associated binder 1 (GAB1) docking/scaffold protein is a key mediator of the MET-tyrosine kinase receptor activated by hepatocyte growth factor/scatter factor (HGF/SF). Activated MET promotes recruitment and tyrosine phosphorylation of GAB1, which in turn recruits multiple proteins and mediates MET signaling leading to cell survival, motility, and morphogenesis. We previously reported that, without its ligand, MET is a functional caspase target during apoptosis, allowing the generation of a p40-MET fragment that amplifies apoptosis. In this study we established that GAB1 is also a functional caspase target by evidencing a caspase-cleaved p35-GAB1 fragment that contains the MET binding domain. GAB1 is cleaved by caspases before MET, and the resulting p35-GAB1 fragment is phosphorylated by MET upon HGF/SF binding and can interact with a subset of GAB1 partners, PI3K, and GRB2 but not with SHP2. This p35-GAB1 fragment favors cell survival by maintaining HGF/SF-induced MET activation of AKT and by hindering p40-MET pro-apoptotic function. These data demonstrate an anti-apoptotic role of caspase-cleaved GAB1 in HGF/SF-MET signaling. PMID:22915589

Lessons from the Short GRB 170817A: The First Gravitational-wave Detection of a Binary Neutron Star Merger

NASA Astrophysics Data System (ADS)

Granot, Jonathan; Guetta, Dafne; Gill, Ramandeep

2017-12-01

The first, long-awaited, detection of a gravitational-wave (GW) signal from the merger of a binary neutron star (NS-NS) system was finally achieved (GW170817) and was also accompanied by an electromagnetic counterpart—the short-duration gamma-ray burst (GRB) 170817A. It occurred in the nearby (D≈ 40 Mpc) elliptical galaxy NGC 4993 and showed optical, IR, and UV emission from half a day up to weeks after the event, as well as late-time X-ray (at ≥slant 8.9 days) and radio (at ≥slant 16.4 days) emission. There was a delay of {{Δ }}t≈ 1.74 {{s}} between the GW merger chirp signal and the prompt GRB emission onset, and an upper limit of {θ }{obs}< 28^\\circ was set on the viewing angle w.r.t the jet’s symmetry axis from the GW signal. In this letter we examine some of the implications of these groundbreaking observations. The delay {{Δ }}t sets an upper limit on the prompt GRB emission radius, {R}γ ≲ 2c{{Δ }}t/{({θ }{obs}-{θ }0)}2, for a jet with sharp edges at an angle {θ }0< {θ }{obs}. GRB 170817A’s relatively low isotropic equivalent γ-ray energy output may suggest a viewing angle slightly outside the jet’s sharp edge, {θ }{obs}-{θ }0˜ {(0.05-0.1)({{Γ }}/100)}-1, but its peak ν {F}ν photon energy and afterglow emission suggest instead that the jet does not have sharp edges and the prompt emission was dominated by less energetic material along our line of sight, at {θ }{obs}≳ 2{θ }0. Finally, we consider the type of remnant that is produced by the NS-NS merger and find that a relatively long-lived (> 2 s) massive NS is strongly disfavored, while a hyper-massive NS of lifetime ˜ 1 {{s}} appears to be somewhat favored over the direct formation of a black hole.

Domain requirements for the Dock adapter protein in growth- cone signaling

PubMed Central

Rao, Yong; Zipursky, S. Lawrence

1998-01-01

Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons. PMID:9482841

Domain requirements for the Dock adapter protein in growth- cone signaling.

PubMed

Rao, Y; Zipursky, S L

1998-03-03

Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression

PubMed Central

Peter, Daniel; Weber, Ramona; Sandmeir, Felix; Wohlbold, Lara; Helms, Sigrun; Bawankar, Praveen; Valkov, Eugene; Igreja, Cátia; Izaurralde, Elisa

2017-01-01

The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5′ cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine–tyrosine–phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP–GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity. PMID:28698298

MITSuME Telescope Observation of GRB080506

NASA Astrophysics Data System (ADS)

Mori, Y. A.; Kawai, N.; Arimoto, M.; Yoshida, M.; Ohta, K.

2009-05-01

We report the multicolor early afterglow observation of a 200 s-long GRB080506 with the 50 cm MITSuME Telescopes at Akeno and Okayama, Japan. We started observations of the afterglow at 117 s after the trigger at Akeno when the prompt emission was still ongoing, and 253 s after the trigger at Okayama. We find no counterpart for the X-ray flare in the optical light curve, implying that the X-ray and optical emission in the early afterglow have different origins. We also found a temporal break at about 1000 s in the optical light curve, which we interpret as the passing of the spectral peak at νm and derive constraints on the physical parameters based on the synchrotron shock model. The SED in the optical band suggests a significant absorption in the host galaxy, well fitted with the LMC dust model with E(B-V)~0.2 and redshift z~2.2.

MONSTER IN THE DARK: THE ULTRALUMINOUS GRB 080607 AND ITS DUSTY ENVIRONMENT

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

Perley, D. A.; Morgan, A. N.; Miller, A. A.

2011-02-15

We present early-time optical through infrared photometry of the bright Swift gamma-ray burst (GRB) 080607, starting only 6 s following the initial trigger in the rest frame. Complemented by our previously published spectroscopy, this high-quality photometric data set allows us to solve for the extinction properties of the redshift 3.036 sightline, giving perhaps the most detailed information to date on the ultraviolet continuum absorption properties of any sightline outside our Local Group. The extinction properties are not adequately modeled by any ordinary extinction template (including the average Milky Way, Large Magellanic Cloud, and Small Magellanic Cloud curves), partially because themore » 2175 A feature (while present) is weaker by about a factor of two than when seen under similar circumstances locally. However, the spectral energy distribution is exquisitely fitted by the more general Fitzpatrick and Massa parameterization of Local-Group extinction, putting it in the same family as some peculiar Milky Way extinction curves. After correcting for this (considerable, A{sub V} = 3.3 {+-} 0.4 mag) extinction, GRB 080607 is revealed to have been among the most optically luminous events ever observed, comparable to the naked-eye burst GRB 080319B. Its early peak time (t{sub rest} < 6 s) indicates a high initial Lorentz factor ({Gamma}>600), while the extreme luminosity may be explained in part by a large circumburst density. Only because of its early high luminosity could the afterglow of GRB 080607 be studied in such detail in spite of the large attenuation and great distance, making this burst an excellent prototype for the understanding of other highly obscured extragalactic objects, and of the class of 'dark' GRBs in particular.« less

[Quasi-adaptive response to alkylating agents in Escherichia coli and Ada-protein functions].

PubMed

Vasil'eva, S V; Moshkovskaia, E Iu; Terekhov, A S; Mikoian, V D; Vanin, A F

2008-01-01

In 2005 we have described in exponentially growing E. coli cells a new fundamental genetic phenomenon,--quasi-adaptive response to alkylating compounds (quasi-Ada). Phenotypic expression of quasi-Ada is similar to the true Ada response. However, in contrast to the letter, it develops in the course of pretreatment of the cells by a sublethal dose of nonalkylating agent, an NO-containing dinitrosyl iron complex with glutathione (DNICglu). To reveal the mechanisms of quasi-adaptation and its association with the function of the Ada regulatory protein, here we used a unique property of dual gene expression regulation of aidB1 gene, a part of the Ada-regulon, namely its relative independence from Ada protein in anaerobic conditions. Based on the results of aidB1 gene expression analysis an EPR spectra of E. coli MV2176 cells (aidB1::lacZ) in aerobic and anaerobic conditions after the corresponding treatments, we conclude that the function and the spatial structure of meAda and [(Cys-)2Fe+(NO+)2]Ada are identical and thus the nitrosylated protein represents a regulator of the Ada regulon gene expression during quasi-adaptation development.

A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance.

PubMed

Clemens, J C; Ursuliak, Z; Clemens, K K; Price, J V; Dixon, J E

1996-07-19

We have used the yeast two-hybrid system to isolate a novel Drosophila adapter protein, which interacts with the Drosophila protein-tyrosine phosphatase (PTP) dPTP61F. Absence of this protein in Drosophila causes the mutant photoreceptor axon phenotype dreadlocks (dock) (Garrity, P. A., Rao, Y., Salecker, I., and Zipursky, S. L.(1996) Cell 85, 639-650). Dock is similar to the mammalian oncoprotein Nck and contains three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain. The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments. A sequence containing five PXXP motifs from the non-catalytic domain of the PTP is sufficient for interaction with Dock. This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock. Immune precipitations of Dock also co-precipitate two tyrosine-phosphorylated proteins having molecular masses of 190 and 145 kDa. Interactions between Dock and these tyrosine-phosphorylated proteins are likely mediated by the Dock SH2 domain. These findings identify potential signal-transducing partners of Dock and propose a role for dPTP61F and the unidentified phosphoproteins in axonal guidance.

FERMI Observations of GRB 090902B: A Distinct Spectral Component in the Prompt and Delayed Emission

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-11-03

Here, we report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. This was one of the brightest GRBs to have been observed by the LAT, which detected several hundred photons during the prompt phase. With a redshift of z = 1.822, this burst is among the most luminous detected by Fermi. Time-resolved spectral analysis reveals a significant power-law component in the LAT data that is distinct from the usual Band model emission that is seen in the sub-MeV energy range.more » This power-law component appears to extrapolate from the GeV range to the lowest energies and is more intense than the Band component, both below ~50 keV and above 100 MeV. The Band component undergoes substantial spectral evolution over the entire course of the burst, while the photon index of the power-law component remains constant for most of the prompt phase, then hardens significantly toward the end. After the prompt phase, power-law emission persists in the LAT data as late as 1 ks post-trigger, with its flux declining as t –1.5. The LAT detected a photon with the highest energy so far measured from a GRB, 33.4 +2.7 –3.5 GeV. This event arrived 82 s after the GBM trigger and ~50 s after the prompt phase emission had ended in the GBM band. In conclusion, we discuss the implications of these results for models of GRB emission and for constraints on models of the extragalactic background light.« less

Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes.

PubMed

Sonntag, Yonathan; Musgaard, Maria; Olesen, Claus; Schiøtt, Birgit; Møller, Jesper Vuust; Nissen, Poul; Thøgersen, Lea

2011-01-01

The structural elucidation of membrane proteins continues to gather pace, but we know little about their molecular interactions with the lipid environment or how they interact with the surrounding bilayer. Here, with the aid of low-resolution X-ray crystallography, we present direct structural information on membrane interfaces as delineated by lipid phosphate groups surrounding the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) in its phosphorylated and dephosphorylated Ca(2+)-free forms. The protein-lipid interactions are further analysed using molecular dynamics simulations. We find that SERCA adapts to membranes of different hydrophobic thicknesses by inducing local deformations in the lipid bilayers and by undergoing small rearrangements of the amino-acid side chains and helix tilts. These mutually adaptive interactions allow smooth transitions through large conformational changes associated with the transport cycle of SERCA, a strategy that may be of general nature for many membrane proteins.

Structural flexibility and protein adaptation to temperature: Molecular dynamics analysis of malate dehydrogenases of marine molluscs.

PubMed

Dong, Yun-Wei; Liao, Ming-Ling; Meng, Xian-Liang; Somero, George N

2018-02-06

Orthologous proteins of species adapted to different temperatures exhibit differences in stability and function that are interpreted to reflect adaptive variation in structural "flexibility." However, quantifying flexibility and comparing flexibility across proteins has remained a challenge. To address this issue, we examined temperature effects on cytosolic malate dehydrogenase (cMDH) orthologs from differently thermally adapted congeners of five genera of marine molluscs whose field body temperatures span a range of ∼60 °C. We describe consistent patterns of convergent evolution in adaptation of function [temperature effects on K M of cofactor (NADH)] and structural stability (rate of heat denaturation of activity). To determine how these differences depend on flexibilities of overall structure and of regions known to be important in binding and catalysis, we performed molecular dynamics simulation (MDS) analyses. MDS analyses revealed a significant negative correlation between adaptation temperature and heat-induced increase of backbone atom movements [root mean square deviation (rmsd) of main-chain atoms]. Root mean square fluctuations (RMSFs) of movement by individual amino acid residues varied across the sequence in a qualitatively similar pattern among orthologs. Regions of sequence involved in ligand binding and catalysis-termed mobile regions 1 and 2 (MR1 and MR2), respectively-showed the largest values for RMSF. Heat-induced changes in RMSF values across the sequence and, importantly, in MR1 and MR2 were greatest in cold-adapted species. MDS methods are shown to provide powerful tools for examining adaptation of enzymes by providing a quantitative index of protein flexibility and identifying sequence regions where adaptive change in flexibility occurs.

f (T ) gravity after GW170817 and GRB170817A

NASA Astrophysics Data System (ADS)

Cai, Yi-Fu; Li, Chunlong; Saridakis, Emmanuel N.; Xue, Ling-Qin

2018-05-01

The combined observation of GW170817 and its electromagnetic counterpart GRB170817A reveals that gravitational waves propagate at the speed of light in high precision. We apply the standard analysis of cosmological perturbations, as well as the effective field theory approach, to investigate the experimental consequences for the theory of f (T ) gravity. Our analysis verifies for the first time that the speed of gravitational waves within f (T ) gravity is equal to the light speed, and hence, the constraints from GW170817 and GRB170817A are trivially satisfied. Nevertheless, by examining the dispersion relation and the frequency of cosmological gravitational waves, we observe a deviation from the results of general relativity, quantified by a new parameter. Although its value is relatively small in viable f (T ) models, its possible future measurement in advancing gravitational-wave astronomy would be the smoking gun of testing this type of modified gravity.

A Correlated Optical and Gamma Emission from GRB 081126A

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

Gendre, B.; Klotz, A.; CESR, Observatoire Midi-Pyrenees, CNRS, Universite de Toulouse, BP 4346, F-31028-Toulouse Cedex 04

2010-10-15

We present an analysis of time-resolved optical emissions observed from the gamma-ray burst GRB 081126 during the prompt phase. The analysis employed time-resolved photometry using optical data obtained by the TAROT telescope, BAT data from the Swift spacecraft and time-resolved spectroscopy at high energies from the GBM instrument onboard the Fermi spacecraft. The optical emission of GRB 081126 is found to be compatible with the second gamma emission pulse shifted by a positive time-lag of 8.4{+-}3.9 sec. This is the first well resolved observation of a time lag between optical and gamma emissions during a gamma-ray burst. Our observations couldmore » potentially provide new constraints on the fireball model for gamma ray burst early emissions. Furthermore, observations of time-lags between optical and gamma ray photons provides an exciting opportunity to constrain quantum gravity theories.« less

GIANT X-RAY BUMP IN GRB 121027A: EVIDENCE FOR FALL-BACK DISK ACCRETION

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

Wu Xuefeng; Hou Shujin; Lei Weihua, E-mail: xfwu@pmo.ac.cn, E-mail: leiwh@hust.edu.cn

2013-04-20

A particularly interesting discovery in observations of GRB 121027A is that of a giant X-ray bump detected by the Swift/X-Ray Telescope. The X-ray afterglow re-brightens sharply at {approx}10{sup 3} s after the trigger by more than two orders of magnitude in less than 200 s. This X-ray bump lasts for more than 10{sup 4} s. It is quite different from typical X-ray flares. In this Letter we propose a fall-back accretion model to interpret this X-ray bump within the context of the collapse of a massive star for a long-duration gamma-ray burst. The required fall-back radius of {approx}3.5 Multiplication-Sign 10{supmore » 10} cm and mass of {approx}0.9-2.6 M{sub Sun} imply that a significant part of the helium envelope should survive through the mass loss during the last stage of the massive progenitor of GRB 121027A.« less

A possible macronova in the late afterglow of the long-short burst GRB 060614.

PubMed

Yang, Bin; Jin, Zhi-Ping; Li, Xiang; Covino, Stefano; Zheng, Xian-Zhong; Hotokezaka, Kenta; Fan, Yi-Zhong; Piran, Tsvi; Wei, Da-Ming

2015-06-11

Long-duration (>2 s) γ-ray bursts that are believed to originate from the death of massive stars are expected to be accompanied by supernovae. GRB 060614, that lasted 102 s, lacks a supernova-like emission down to very stringent limits and its physical origin is still debated. Here we report the discovery of near-infrared bump that is significantly above the regular decaying afterglow. This red bump is inconsistent with even the weakest known supernova. However, it can arise from a Li-Paczyński macronova--the radioactive decay of debris following a compact binary merger. If this interpretation is correct, GRB 060614 arose from a compact binary merger rather than from the death of a massive star and it was a site of a significant production of heavy r-process elements. The significant ejected mass favours a black hole-neutron star merger but a double neutron star merger cannot be ruled out.

M. tuberculosis-Initiated Human Mannose Receptor Signaling Regulates Macrophage Recognition and Vesicle Trafficking by FcRγ-Chain, Grb2, and SHP-1.

PubMed

Rajaram, Murugesan V S; Arnett, Eusondia; Azad, Abul K; Guirado, Evelyn; Ni, Bin; Gerberick, Abigail D; He, Li-Zhen; Keler, Tibor; Thomas, Lawrence J; Lafuse, William P; Schlesinger, Larry S

2017-10-03

Despite its prominent role as a C-type lectin (CTL) pattern recognition receptor, mannose receptor (MR, CD206)-specific signaling molecules and pathways are unknown. The MR is highly expressed on human macrophages, regulating endocytosis, phagocytosis, and immune responses and mediating Mycobacterium tuberculosis (M.tb) phagocytosis by human macrophages, thereby limiting phagosome-lysosome (P-L) fusion. We identified human MR-associated proteins using phosphorylated and non-phosphorylated MR cytoplasmic tail peptides. We found that MR binds FcRγ-chain, which is required for MR plasma membrane localization and M.tb cell association. Additionally, we discovered that MR-mediated M.tb association triggers immediate MR tyrosine residue phosphorylation and Grb2 recruitment, activating the Rac/Pak/Cdc-42 signaling cascade important for M.tb uptake. MR activation subsequently recruits SHP-1 to the M.tb-containing phagosome, where its activity limits PI(3)P generation at the phagosome and M.tb P-L fusion and promotes M.tb growth. In sum, we identify human MR signaling pathways that temporally regulate phagocytosis and P-L fusion during M.tb infection. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Afterglows and Kilonovae Associated with Nearby Low-luminosity Short-duration Gamma-Ray Bursts: Application to GW170817/GRB 170817A

NASA Astrophysics Data System (ADS)

Xiao, Di; Liu, Liang-Duan; Dai, Zi-Gao; Wu, Xue-Feng

2017-12-01

Very recently, the gravitational-wave (GW) event GW170817 was discovered to be associated with the short gamma-ray burst (GRB) 170817A. Multi-wavelength follow-up observations were carried out, and X-ray, optical, and radio counterparts to GW170817 were detected. The observations undoubtedly indicate that GRB 170817A originates from a binary neutron star merger. However, the GRB falls into the low-luminosity class that could have a higher statistical occurrence rate and detection probability than the normal (high-luminosity) class. This implies the possibility that GRB 170817A is intrinsically powerful, but we are off-axis and only observe its side emission. In this Letter, we provide a timely modeling of the multi-wavelength afterglow emission from this GRB and the associated kilonova signal from the merger ejecta, under the assumption of a structured jet, a two-component jet, and an intrinsically less-energetic quasi-isotropic fireball, respectively. Comparing the afterglow properties with the multi-wavelength follow-up observations, we can distinguish between these three models. Furthermore, a few model parameters (e.g., the ejecta mass and velocity) can be constrained.

Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression.

PubMed

Schaper, F; Gendo, C; Eck, M; Schmitz, J; Grimm, C; Anhuf, D; Kerr, I M; Heinrich, P C

1998-11-01

Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via the IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in the regulation of acute-phase protein genes in liver cells. Ligand binding to the receptor complex leads to tyrosine phosphorylation and activation of Janus kinases (Jak), phosphorylation of the signal transducing subunit gp130, followed by recruitment and phosphorylation of the signal transducer and activator of transcription factors STAT3 and STAT1 and the src homology domain (SH2)-containing protein tyrosine phosphatase (SHP2). The tyrosine phosphorylated STAT factors dissociate from the receptor, dimerize and translocate to the nucleus where they bind to enhancer sequences of IL-6 target genes. Phosphorylated SHP2 is able to bind growth factor receptor bound protein (grb2) and thus might link the Jak/STAT pathway to the ras/raf/mitogen-activated protein kinase pathway. Here we present data on the dose-dependence, kinetics and kinase requirements for SHP2 phosphorylation after the activation of the signal transducer, gp130, of the IL-6-type family receptor complex. When human fibrosarcoma cell lines deficient in Jak1, Jak2 or tyrosine kinase 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only in Jak1-, but not in Jak 2- or Tyk2-deficient cells, SHP2 activation was greatly impaired. It is concluded that Jak1 is required for the tyrosine phosphorylation of SHP2. This phosphorylation depends on Tyr-759 in the cytoplasmatic domain of gp130, since a Tyr-759-->Phe exchange abrogates SHP2 activation and in turn leads to elevated and prolonged STAT3 and STAT1 activation as well as enhanced acute-phase protein gene induction. Therefore, SHP2 plays an important role in acute-phase gene regulation.

Multiband Optical Follow-Up Observations of GRB 020813 AT KISO and Bisei Observatories

NASA Astrophysics Data System (ADS)

Urata, Y.; Nishiura, S.; Miyata, T.; Mito, H.; Kawabata, T.; Nakada, Y.; Aoki, T.; Soyano, T.; Tarusawa, K.; Yoshida, A.; Tamagawa, T.; Makishima, K.

Four color (l B,V,R,I) photometric observations of the optical afterglow of GRB 020813 were obtained from 0.346 to 0.516 days after the burst. In order to investigate the early-time (<1 day) evolution of the afterglow, four-band light curves were produced by analyzing the data taken at these two sites, as well as publicly released data taken by the Magellan Baade telescope. The light curves can be approximated by a broken power law, of which the indices are approximately 0.46 and 1.33 before and after a break at ˜0.2 days, respectively. The optical spectral index stayed approximately constant at ˜0.9 over 0.17--4.07 days after the burst. Since the temporal decay index after the break and the spectral index measured at that time are both consistent with those predicted by a spherical expansion model, the early break is unlikely to be a jet break, but likely to represent the end of an early bump in the light curve as was observed in the optical afterglow of GRB 021004.

Missing GRB host galaxies in deep mid-infrared observations: implications on the use of GRBs as star formation tracers

NASA Astrophysics Data System (ADS)

Le Floc'h, Emeric; Charmandaris, Vassilis; Forrest, Bill; Mirabel, Félix; Armus, Lee; Devost, Daniel

2006-05-01

We report on the first mid-infrared observations of 16 GRB host galaxies performed with the Spitzer Space Telescope, and investigate the presence of evolved stellar populations and dust-enshrouded star-forming activity associated with GRBs. Only a very small fraction of our sample is detected by Spitzer, which is not consistent with recent works suggesting the presence of a GRB host population dominated by massive and strongly-starbursting galaxies (SFR >~ 100Msolaryr-1). Should the GRB hosts be representative of star-forming galaxies at high redshift, models of galaxy evolution indicate that >~ 50% of GRB hosts would be easily detected at the depth of our mid-infrared observations. Unless our sample suffers from a strong observational bias which remains to be understood, we infer in this context that the GRBs identified with the current techniques can not be directly used as unbiased probes of the global and integrated star formation history of the Universe.

Aerobic Exercise Training Adaptations Are Increased by Postexercise Carbohydrate-Protein Supplementation

PubMed Central

Ferguson-Stegall, Lisa; McCleave, Erin; Ding, Zhenping; Doerner III, Phillip G.; Liu, Yang; Wang, Bei; Healy, Marin; Kleinert, Maximilian; Dessard, Benjamin; Lassiter, David G.; Kammer, Lynne; Ivy, John L.

2011-01-01

Carbohydrate-protein supplementation has been found to increase the rate of training adaptation when provided postresistance exercise. The present study compared the effects of a carbohydrate and protein supplement in the form of chocolate milk (CM), isocaloric carbohydrate (CHO), and placebo on training adaptations occurring over 4.5 weeks of aerobic exercise training. Thirty-two untrained subjects cycled 60 min/d, 5 d/wk for 4.5 wks at 75–80% of maximal oxygen consumption (VO2 max). Supplements were ingested immediately and 1 h after each exercise session. VO2 max and body composition were assessed before the start and end of training. VO2 max improvements were significantly greater in CM than CHO and placebo. Greater improvements in body composition, represented by a calculated lean and fat mass differential for whole body and trunk, were found in the CM group compared to CHO. We conclude supplementing with CM postexercise improves aerobic power and body composition more effectively than CHO alone. PMID:21773022

Fermi Observations of High-Energy Gamma-Ray Emission from GRB 080916C

DOE PAGES

Abdo, A. A.; Ackermann, M.; Arimoto, M.; ...

2009-02-19

Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. Finally, the known distance of the burstmore » enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.« less

Fermi observations of high-energy gamma-ray emission from GRB 080916C.

PubMed

Abdo, A A; Ackermann, M; Arimoto, M; Asano, K; Atwood, W B; Axelsson, M; Baldini, L; Ballet, J; Band, D L; Barbiellini, G; Baring, M G; Bastieri, D; Battelino, M; Baughman, B M; Bechtol, K; Bellardi, F; Bellazzini, R; Berenji, B; Bhat, P N; Bissaldi, E; Blandford, R D; Bloom, E D; Bogaert, G; Bogart, J R; Bonamente, E; Bonnell, J; Borgland, A W; Bouvier, A; Bregeon, J; Brez, A; Briggs, M S; Brigida, M; Bruel, P; Burnett, T H; Burrows, D; Busetto, G; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Ceccanti, M; Cecchi, C; Celotti, A; Charles, E; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Cominsky, L R; Connaughton, V; Conrad, J; Costamante, L; Cutini, S; Deklotz, M; Dermer, C D; de Angelis, A; de Palma, F; Digel, S W; Dingus, B L; do Couto E Silva, E; Drell, P S; Dubois, R; Dumora, D; Edmonds, Y; Evans, P A; Fabiani, D; Farnier, C; Favuzzi, C; Finke, J; Fishman, G; Focke, W B; Frailis, M; Fukazawa, Y; Funk, S; Fusco, P; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giommi, P; Giordano, F; Glanzman, T; Godfrey, G; Goldstein, A; Granot, J; Greiner, J; Grenier, I A; Grondin, M-H; Grove, J E; Guillemot, L; Guiriec, S; Haller, G; Hanabata, Y; Harding, A K; Hayashida, M; Hays, E; Hernando Morat, J A; Hoover, A; Hughes, R E; Jóhannesson, G; Johnson, A S; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, T; Katagiri, H; Kataoka, J; Kavelaars, A; Kawai, N; Kelly, H; Kennea, J; Kerr, M; Kippen, R M; Knödlseder, J; Kocevski, D; Kocian, M L; Komin, N; Kouveliotou, C; Kuehn, F; Kuss, M; Lande, J; Landriu, D; Larsson, S; Latronico, L; Lavalley, C; Lee, B; Lee, S-H; Lemoine-Goumard, M; Lichti, G G; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Madejski, G M; Makeev, A; Marangelli, B; Mazziotta, M N; McBreen, S; McEnery, J E; McGlynn, S; Meegan, C; Mészáros, P; Meurer, C; Michelson, P F; Minuti, M; Mirizzi, N; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Moretti, E; Morselli, A; Moskalenko, I V; Murgia, S; Nakamori, T; Nelson, D; Nolan, P L; Norris, J P; Nuss, E; Ohno, M; Ohsugi, T; Okumura, A; Omodei, N; Orlando, E; Ormes, J F; Ozaki, M; Paciesas, W S; Paneque, D; Panetta, J H; Parent, D; Pelassa, V; Pepe, M; Perri, M; Pesce-Rollins, M; Petrosian, V; Pinchera, M; Piron, F; Porter, T A; Preece, R; Rainò, S; Ramirez-Ruiz, E; Rando, R; Rapposelli, E; Razzano, M; Razzaque, S; Rea, N; Reimer, A; Reimer, O; Reposeur, T; Reyes, L C; Ritz, S; Rochester, L S; Rodriguez, A Y; Roth, M; Ryde, F; Sadrozinski, H F-W; Sanchez, D; Sander, A; Saz Parkinson, P M; Scargle, J D; Schalk, T L; Segal, K N; Sgrò, C; Shimokawabe, T; Siskind, E J; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Stamatikos, M; Starck, J-L; Stecker, F W; Steinle, H; Stephens, T E; Strickman, M S; Suson, D J; Tagliaferri, G; Tajima, H; Takahashi, H; Takahashi, T; Tanaka, T; Tenze, A; Thayer, J B; Thayer, J G; Thompson, D J; Tibaldo, L; Torres, D F; Tosti, G; Tramacere, A; Turri, M; Tuvi, S; Usher, T L; van der Horst, A J; Vigiani, L; Vilchez, N; Vitale, V; von Kienlin, A; Waite, A P; Williams, D A; Wilson-Hodge, C; Winer, B L; Wood, K S; Wu, X F; Yamazaki, R; Ylinen, T; Ziegler, M

2009-03-27

Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.

First measurement of H I 21 cm emission from a GRB host galaxy indicates a post-merger system

NASA Astrophysics Data System (ADS)

Arabsalmani, Maryam; Roychowdhury, Sambit; Zwaan, Martin A.; Kanekar, Nissim; Michałowski, Michał J.

2015-11-01

We report the detection and mapping of atomic hydrogen in H I 21 cm emission from ESO 184-G82, the host galaxy of the gamma-ray burst 980425. This is the first instance where H I in emission has been detected from a galaxy hosting a gamma-ray burst (GRB). ESO 184-G82 is an isolated galaxy and contains a Wolf-Rayet region close to the location of the GRB and the associated supernova, SN 1998bw. This is one of the most luminous H II regions identified in the local Universe, with a very high inferred density of star formation. The H I 21 cm observations reveal a high H I mass for the galaxy, twice as large as the stellar mass. The spatial and velocity distribution of the H I 21 cm emission reveals a disturbed rotating gas disc, which suggests that the galaxy has undergone a recent minor merger that disrupted its rotation. We find that the Wolf-Rayet region and the GRB are both located in the highest H I column density region of the galaxy. We speculate that the merger event has resulted in shock compression of the gas, triggering extreme star formation activity, and resulting in the formation of both the Wolf-Rayet region and the GRB. The high H I column density environment of the GRB is consistent with the high H I column densities seen in absorption in the host galaxies of high-redshift GRBs.

Extremely Soft X-Ray Flash as the Indicator of Off-axis Orphan GRB Afterglow

NASA Astrophysics Data System (ADS)

Urata, Yuji; Huang, Kuiyun; Yamazaki, Ryo; Sakamoto, Takanori

2015-06-01

We verified the off-axis jet model of X-ray flashes (XRFs) and examined a discovery of off-axis orphan gamma-ray burst (GRB) afterglows. The XRF sample was selected on the basis of the following three factors: (1) a constraint on the lower peak energy of the prompt spectrum {E}{obs}{src}, (2) redshift measurements, and (3) multicolor observations of an earlier (or brightening) phase. XRF 020903 was the only sample selected on the basis of these criteria. A complete optical multicolor afterglow light curve of XRF 020903 obtained from archived data and photometric results in the literature showed an achromatic brightening around 0.7 days. An off-axis jet model with a large observing angle (0.21 rad, which is twice the jet opening half-angle, {θ }{jet}) can naturally describe the achromatic brightening and the prompt X-ray spectral properties. This result indicates the existence of off-axis orphan GRB afterglow light curves. Events with a larger viewing angle (\\gt ∼ 2{θ }{jet}) could be discovered using an 8 m class telescope with wide-field imagers such as the Subaru Hyper-Suprime-Cam and the Large Synoptic Survey Telescope.

SN 2013dx associated with GRB 130702A: a detailed photometric and spectroscopic monitoring and a study of the environment

NASA Astrophysics Data System (ADS)

D'Elia, V.; Pian, E.; Melandri, A.; D'Avanzo, P.; Della Valle, M.; Mazzali, P. A.; Piranomonte, S.; Tagliaferri, G.; Antonelli, L. A.; Bufano, F.; Covino, S.; Fugazza, D.; Malesani, D.; Møller, P.; Palazzi, E.

2015-05-01

Aims: Long-duration gamma-ray bursts (GRBs) and broad-line, type Ic supernovae (SNe) are strongly connected. We aim at characterizing SN 2013dx, which is associated with GRB 130702A, through a sensitive and extensive ground-based observational campaign in the optical-IR band. Methods: We monitored the field of the Swift GRB 130702A (redshift z = 0.145) using the 8.2 m VLT, the 3.6 m TNG and the 0.6 m REM telescopes during the time interval between 4 and 40 days after the burst. Photometric and spectroscopic observations revealed the associated type Ic SN 2013dx. Our multiband photometry allowed constructing a bolometric light curve. Results: The bolometric light curve of SN 2013dx resembles that of 2003dh (associated with GRB 030329), but is ~10% faster and ~25% dimmer. From this we infer a synthesized 56Ni mass of ~0.2 M⊙. The multi-epoch optical spectroscopy shows that the SN 2013dx behavior is best matched by SN 1998bw, among the other well-known low-redshift SNe associated with GRBs and XRFs, and by SN 2010ah, an energetic type Ic SN not associated with any GRB. The photospheric velocity of the ejected material declines from ~2.7 × 104 km s-1 at 8 rest frame days from the explosion, to ~3.5 × 103 km s-1 at 40 days. These values are extremely close to those of SN1998bw and 2010ah. We deduce for SN 2013dx a kinetic energy of ~35 × 1051 erg and an ejected mass of ~7 M⊙. This suggests that the progenitor of SN2013dx had a mass of ~25-30 M⊙, which is 15-20% less massive than that of SN 1998bw. Finally, we studied the SN 2013dx environment through spectroscopy of the closeby galaxies: 9 out of the 14 inspected galaxies lie within 0.03 in redshift from z = 0.145, indicating that the host of GRB 130702A/SN 2013dx belongs to a group of galaxies, an unprecedented finding for a GRB-associated SN and, to our knowledge, for long GRBs in general. Based on observations collected at the Italian 3.6-m Telescopio Nazionale Galileo (TNG), operated on the island of La

Jet or shock breakout? The low-luminosity GRB 060218

NASA Astrophysics Data System (ADS)

Irwin, Christopher M.; Chevalier, Roger A.

2016-08-01

We consider a model for the low-luminosity gamma-ray burst GRB 060218 that plausibly accounts for multiwavelength observations to day 20. The model components are: (1) a long-lived (tj ˜ 3000 s) central engine and accompanying low-luminosity (Lj ˜ 1047 erg s-1), mildly relativistic (γ ˜ 10) jet; (2) a low-mass (˜4 × 10-3 M⊙) envelope surrounding the progenitor star; and (3) a modest amount of dust (AV ˜ 0.1 mag) in the circumstellar or interstellar environment. Blackbody emission from the transparency radius in a low-power jet outflow can fit the prompt thermal X-ray emission, and the non-thermal X-rays and gamma-rays may be produced via Compton scattering of thermal photons from hot leptons in the jet interior or the external shocks. The later mildly relativistic phase of this outflow can produce the radio emission via synchrotron radiation from the forward shock. Meanwhile, interaction of the associated SN 2006aj with a circumstellar envelope extending to ˜1013 cm can explain the early optical emission. The X-ray afterglow can be interpreted as a light echo of the prompt emission from dust at ˜30 pc. Our model is a plausible alternative to that of Nakar, who recently proposed shock breakout of a jet smothered by an extended envelope as the source of prompt emission. Both our results and Nakar's suggest that bursts such as GRB 060218 may originate from unusual progenitors with extended circumstellar envelopes, and that a jet is necessary to decouple the prompt emission from the supernova.

Implications of Lag-Luminosity Relationship for Unified GRB Paradigms

NASA Technical Reports Server (NTRS)

Norris, J. P.; White, Nicholas E. (Technical Monitor)

2002-01-01

Spectral lags (tau(sub lag)) are deduced for 1437 long (T(sub 90) greater than 2 s) BATSE gamma-ray bursts (GRBs) with peak flux F(sub p) greater than 0.25 photons cm(sup -2)/s, near to the BATSE trigger threshold. The lags are modeled to approximate the observed distribution in the F(sub p)-T(sub lag) plane, realizing a noise-free representation. Assuming a two-branch lag-luminosity relationship, the lags are self-consistently corrected for cosmological effects to yield distributions in luminosity, distance, and redshift. The results have several consequences for GRB populations and for unified gamma-ray/afterglow scenarios which would account for afterglow break times and gamma-ray spectral evolution in terms of jet opening angle, viewing angle, or a profiled jet with variable Lorentz factor: A component of the burst sample is identified - those with few, wide pulses, lags of a few tenths to several seconds, and soft spectra - whose Log[N]-Log[F(sub p)] distribution approximates a -3/2 power-law, suggesting homogeneity and thus relatively nearby sources. The proportion of these long-lag bursts increases from negligible among bright BATSE bursts to approx. 50% at trigger threshold. Bursts with very long lags, approx. 1-2 less than tau(sub lag) (S) less than 10, show a tendency to concentrate near the Supergalactic Plane with a quadrupole moment of approx. -0.10 +/- 0.04. GRB 980425 (SN 1998bw) is a member of this subsample of approx. 90 bursts with estimated distances less than 100 Mpc. The frequency of the observed ultra-low luminosity bursts is approx. 1/4 that of SNe Ib/c within the same volume. If truly nearby, the core-collapse events associated with these GRBs might produce gravitational radiation detectable by LIGO-II. Such nearby bursts might also help explain flattening of the cosmic ray spectrum at ultra-high energies, as observed by AGASA.