| 1. |
- Garnier, P., et al.
(författare)
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Mapping 300 eV electrons at Saturn with the Cassini RPWS Langmuir probe
- 2011
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Ingår i: EPSC-DPS Joint Meeting 2011.
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Konferensbidrag (refereegranskat)abstract
- The Cassini Langmuir probe (onboard RPWS experiment) has provided wealth of information about the kronian cold plasma environment since the Saturn Orbit Insertion in 2004. The usage of the Langmuir probe is based on the fitting of the currentvoltage curve which brings information on several plasma parameters in cold and dense plasma regions. The ion part of the I-V curve may however be influenced by energetic particles hitting the probe, leading to an enhanced ion current measured. We report here the influence of 300 eV electrons on the probe current, with a current belt observed between Dione and Rhea.
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| 2. |
- Garnier, P., et al.
(författare)
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The detection of energetic electrons with the Cassini Langmuir probe at Saturn
- 2012
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. A10202-
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Tidskriftsartikel (refereegranskat)abstract
- The Cassini Langmuir probe, part of the Radio and Plasma Wave Science (RPWS) instrument, has provided a wealth of information about the cold and dense plasma in the Saturnian system. The analysis of the ion side current (current for negative potentials) measured by the probe from 2005 to 2008 reveals also a strong sensitivity to energetic electrons (250-450 eV). These electrons impact the surface of the probe, and generate a detectable current of secondary electrons. A broad secondary electrons current region is inferred from the observations in the dipole L Shell range of similar to 6-10, with a peak full width at half maximum (FWHM) at L = 6.4-9.4 (near the Dione and Rhea magnetic dipole L Shell values). This magnetospheric flux tube region, which displays a large day/night asymmetry, is related to the similar structure in the energetic electron fluxes as the one measured by the onboard Electron Spectrometer (ELS) of the Cassini Plasma Spectrometer (CAPS). It corresponds spatially to both the outer electron radiation belt observed by the Magnetosphere Imaging Instrument (MIMI) at high energies and to the low-energy peak which has been observed since the Voyager era. Finally, a case study suggests that the mapping of the current measured by the Langmuir probe for negative potentials can allow to identify the plasmapause-like boundary recently identified at Saturn, and thus potentially identify the separation between the closed and open magnetic field lines regions.
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| 3. |
- Gawlik, Kinga I., et al.
(författare)
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Potent pro-inflammatory and profibrotic molecules, osteopontin and galectin-3, are not major disease modulators of laminin α2 chaindeficient muscular dystrophy
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chaindeficiency. It is characterized with early inflammation and build-up of fibrotic lesions, both in patients and MDC1A mouse models (e.g. dy3K/dy3K). Despite the enormous impact of inflammation on tissue remodelling in disease, the inflammatory response in MDC1A has been poorly described. Consequently, a comprehensive understanding of secondary mechanisms (impaired regeneration, enhanced fibrosis) leading to deterioration of muscle phenotype in MDC1A is missing. We have monitored inflammatory processes in dy3K/dy3K muscle and created mice deficient in laminin α2 chain and osteopontin or galectin-3, two pro-inflammatory and pro-fibrotic molecules drastically increased in dystrophic muscle. Surprisingly, deletion of osteopontin worsened the phenotype of dy3K/dy3K mice and loss of galectin-3 did not reduce muscle pathology. Our results indicate that osteopontin could even be a beneficial immunomodulator in MDC1A. This knowledge is essential for the design of future therapeutic interventions for muscular dystrophies that aim at targeting inflammation, especially that osteopontin inhibition has been suggested for Duchenne muscular dystrophy therapy.
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| 4. |
- Gawlik, Kinga, et al.
(författare)
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Loss of Dystrophin and β-Sarcoglycan, Respectively, Significantly Exacerbates the Phenotype of Laminin α2 Chain-Deficient Animals.
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 184:3, s. 740-752
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion molecule laminin α2 chain interacts with the dystrophin-glycoprotein complex, contributes to normal muscle function, and protects skeletal muscles from damage. Complete loss of the laminin α2 chain in mice results in a severe muscular dystrophy phenotype and death at approximately 3 weeks of age. However, it is not clear if the remaining members of the dystrophin-glycoprotein complex further protect laminin α2 chain-deficient skeletal muscle fibers from degeneration. Hence, we generated mice deficient in laminin α2 chain and dystrophin (dy(3K)/mdx) and mice devoid of laminin α2 chain and β-sarcoglycan (dy(3K)/Sgcb). Severe muscular dystrophy and a lack of nourishment inevitably led to massive muscle wasting and death in double-knockout animals. The dy(3K)/Sgcb mice were generally more severely affected than dy(3K)/mdx mice. However, both double-knockout strains displayed exacerbated muscle degeneration, inflammation, fibrosis, and reduced life span (5 to 13 days) compared with single-knockout animals. However, neither extraocular nor cardiac muscle was affected in double-knockout animals. Our results suggest that, although laminin α2 chain, dystrophin, and β-sarcoglycan are all part of the same adhesion complex, they have complementary, but nonredundant, roles in maintaining sarcolemmal integrity and protecting skeletal muscle fibers from damage. Moreover, the double-knockout mice could potentially serve as models in which to study extremely aggressive muscle-wasting conditions.
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| 5. |
- Holmberg, Johan K, et al.
(författare)
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Laminin-211 in skeletal muscle function.
- 2012
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Ingår i: Cell Adhesion and Migration. - 1933-6918. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- A chain is no stronger than its weakest link is an old idiom that holds true for muscle biology. As the name implies, skeletal muscle's main function is to move the bones. However, for a muscle to transmit force and withstand the stress that contractions give rise to, it relies on a chain of proteins attaching the cytoskeleton of the muscle fiber to the surrounding extracellular matrix. The importance of this attachment is illustrated by a large number of muscular dystrophies caused by interruption of the cytoskeletal-extracellular matrix interaction. One of the major components of the extracellular matrix is laminin, a heterotrimeric glycoprotein and a major constituent of the basement membrane. It has become increasingly apparent that laminins are involved in a multitude of biological functions, including cell adhesion, differentiation, proliferation, migration and survival. This review will focus on the importance of laminin-211 for normal skeletal muscle function.
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| 6. |
- Holmberg, Johan K, et al.
(författare)
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Laminin α2 Chain-Deficiency is Associated with microRNA Deregulation in Skeletal Muscle and Plasma.
- 2014
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 6:Jul 3
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Tidskriftsartikel (refereegranskat)abstract
- microRNAs (miRNAs) are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A). MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.
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| 7. |
- Holmberg, Madeleine K. G., et al.
(författare)
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Ion densities and velocities in the inner plasma torus of Saturn
- 2012
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 73:1, s. 151-160
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Tidskriftsartikel (refereegranskat)abstract
- We present plasma data from the Cassini Radio and Plasma Wave Science (RPWS) Langmuir probe (LP), mapping the ion density and velocity of Saturn's inner plasma torus. Data from 129 orbits, recorded during the period from the 1st of February 2005 to the 27th of June 2010, are used to map the extension of the inner plasma torus. The dominant part of the plasma torus is shown to be located in between 2.5 and 8 Saturn radii (1 RS=60,268 km) from the planet, with a north-southward extension of ±2RS. The plasma disk ion density shows a broad maximum in between the orbits of Enceladus and Tethys. Ion density values vary between 20 and 125 cm-3 at the location of the density maximum, indicating considerable dynamics of the plasma disk. The equatorial density structure, |z|<0.5RS, shows a slower decrease away from the planet than towards. The outward decrease, from 5 R S, is well described by the relation neq=2.2×10 4(1/R)3.63. The plume of the moon Enceladus is clearly visible as an ion density maximum of 105 cm-3, only present at the south side of the ring plane. A less prominent density peak, of 115 cm-3, is also detected at the orbit of Tethys, at ∼4.9 RS. No density peaks are recorded at the orbits of the moons Mimas, Dione, and Rhea. The presented ion velocity vi,θ shows a clear general trend in the region between 3 and 7 RS, described by vi, θ=1.5R2-8.7R+39. The average vi,θ starts to deviate from corotation at around 3 RS, reaching ∼68% of corotation close to 5 RS.
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| 8. |
- Häger, Mattias, et al.
(författare)
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Cib2 binds integrin a7Bb1D and is reduced in laminin a2 chain deficient muscular dystrophy
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:36, s. 24760-24769
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the gene encoding laminin alpha 2 chain cause congenital muscular dystrophy type 1A. In skeletal muscle, laminin alpha 2 chain binds at least two receptor complexes: the dystrophin-glycoprotein complex and integrin alpha 7 beta 1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin alpha 2 chain-deficient mouse limb muscle. One of the down-regulated genes encodes a protein called Cib2 (calcium-and integrin-binding protein 2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin alpha IIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin alpha 7 beta 1-binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle, Cib2 colocalizes with the integrin alpha 7B subunit at the sarcolemma and at the neuromuscular and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium-binding protein that interacts with integrin alpha 7B beta 1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin alpha 7B beta 1D signaling in skeletal muscle.
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| 9. |
- Körner, Zandra, et al.
(författare)
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Bortezomib Partially Improves Laminin α2 Chain-Deficient Muscular Dystrophy.
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 184:5, s. 1518-1528
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Tidskriftsartikel (refereegranskat)abstract
- Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted.
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| 10. |
- Moreira Soares Oliveira, Bernardo, et al.
(författare)
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Absence of microRNA-21 does not reduce muscular dystrophy in mouse models of LAMA2-CMD
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are short non-coding RNAs that modulate gene expression post-transcriptionally. Current evidence suggests that miR-21 plays a significant role in the progression of fibrosis in muscle diseases. Laminin-deficient congenital muscular dystrophy (LAMA2-CMD) is a severe form of congenital muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. Mouse models dy3K/dy3K and dy2J/dy2J, respectively, adequately mirror severe and milder forms of LAMA2-CMD. Both human and mouse LAMA2-CMD muscles are characterized by extensive fibrosis and considering that fibrosis is the final step that destroys muscle during the disease course, anti-fibrotic therapies may be effective strategies for prevention of LAMA2-CMD. We have previously demonstrated a significant up-regulation of the pro-fibrotic miR-21 in dy3K/dy3K and dy2J/dy2J skeletal muscle. Hence, the objective of this study was to explore if absence of miR-21 reduces fibrogenesis and improves the phenotype of LAMA2-CMD mice. Thus, we generated dy3K/dy3K and dy2J/dy2J mice devoid of miR-21 (dy3K/miR-21 and dy2J/miR-21 mice, respectively). However, the muscular dystrophy phenotype of dy3K/miR-21 and dy2J/miR-21 double knock-out mice was not improved compared to dy3K/dy3K or dy2J/dy2J mice, respectively. Mice displayed the same body weight, dystrophic muscles (with fibrosis) and impaired muscle function. These data indicate that miR-21 may not be involved in the development of fibrosis in LAMA2-CMD.
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