33 research outputs found
Characterisation of expression patterns and functional role of Cactin in early zebrafish development
The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts
sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines
and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that
plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in
different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule
is involved in specific developmental events. In the present study we employ zebrafish as a model
to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development.
Cactin was first characterised in Drosophila as a new member of the Rel pathway that could
affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin
in zebrafish, we initially investigated its expression pattern and functional role during early embryonic
developmental stages. We detect Cactin expression at all stages of early development and knockdown
of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested
by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly
conserved during evolution and plays a key role in early embryonic development
Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10
TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five
intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene
expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR
adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information
on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing
activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4
ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase
2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on
Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated
factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor
SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38
MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of
MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream
regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen
Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10
TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five
intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene
expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR
adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information
on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing
activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4
ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase
2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on
Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated
factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor
SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38
MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of
MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream
regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen
Characterisation of expression patterns and functional role of Cactin in early zebrafish development
The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts
sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines
and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that
plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in
different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule
is involved in specific developmental events. In the present study we employ zebrafish as a model
to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development.
Cactin was first characterised in Drosophila as a new member of the Rel pathway that could
affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin
in zebrafish, we initially investigated its expression pattern and functional role during early embryonic
developmental stages. We detect Cactin expression at all stages of early development and knockdown
of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested
by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly
conserved during evolution and plays a key role in early embryonic development
The Gaia mission
Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai
Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10
TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five
intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene
expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR
adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information
on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing
activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4
ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase
2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on
Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated
factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor
SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38
MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of
MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream
regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen
Characterisation of expression patterns and functional role of Cactin in early zebrafish development
The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts
sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines
and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that
plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in
different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule
is involved in specific developmental events. In the present study we employ zebrafish as a model
to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development.
Cactin was first characterised in Drosophila as a new member of the Rel pathway that could
affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin
in zebrafish, we initially investigated its expression pattern and functional role during early embryonic
developmental stages. We detect Cactin expression at all stages of early development and knockdown
of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested
by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly
conserved during evolution and plays a key role in early embryonic development
Characterisation of expression patterns and functional role of Cactin in early zebrafish development
The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts
sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines
and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that
plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in
different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule
is involved in specific developmental events. In the present study we employ zebrafish as a model
to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development.
Cactin was first characterised in Drosophila as a new member of the Rel pathway that could
affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin
in zebrafish, we initially investigated its expression pattern and functional role during early embryonic
developmental stages. We detect Cactin expression at all stages of early development and knockdown
of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested
by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly
conserved during evolution and plays a key role in early embryonic development