905 research outputs found
CCN5/WISP2 and metabolic diseases.
This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s12079-017-0437-zObesity and type 2 diabetes increase worldwide at an epidemic rate. It is expected that by the year 2030 around 500 million people will have diabetes; predominantly type 2 diabetes. The CCN family of proteins has become of interest in both metabolic and other common human diseases because of their effects on mesenchymal stem cell (MSCs) proliferation and differentiation as well as being important regulators of fibrosis. We here review current knowledge of the WNT1 inducible signaling pathway protein 2 (CCN5/WISP2). It has been shown to be an important regulator of both these processes through effects on both the canonical WNT and the TGFÎČ pathways. It is also under normal regulation by the adipogenic commitment factor BMP4, in contrast to conventional canonical WNT ligands, and allows MSCs to undergo normal adipose cell differentiation. CCN5/WISP2 is highly expressed in, and secreted by, MSCs and is an important regulator of MSCs growth. In a transgenic mouse model overexpressing CCN5/WISP2 in the adipose tissue, we have shown that it is secreted and circulating in the blood, the mice develop hypercellular white and brown adipose tissue, have increased lean body mass and enlarged hypercellular hearts. Obese transgenic mice had improved insulin sensitivity. Interestingly, the anti-fibrotic effect of CCN5/WISP2 is protective against heart failure by inhibition of the TGFÎČ pathway. Understanding how CCN5/WISP2 is regulated and signals is important and may be useful for developing new treatment strategies in obesity and metabolic diseases and it can also be a target in regenerative medicine.The studies in the authorsâ laboratory are supported by grants from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement (n° 608765), Henning and Johan Throne- Holstâs foundation for the promotion of scientific research, the Medical Research Council, Torsten Söderberg Foundation, Novo Nordisk Foundation, EFSD, Swedish Diabetes Foundation, Swedish ALF funds, Edgar Sjölund Foundation, Wilhelm and Martina Lundgrenâs Foundation, the Magnus Bergvall Foundation, Lisa and Johan Grönberg Foundation, Göteborgs Diabetesförening, Sigurd and Elsa Goljeâs Foundation, and the EUâs FP7 program (n°607842)
BMP4 gene therapy enhances insulin sensitivity but not adipose tissue browning in obese mice
Bone morphogenetic protein 4 (BMP4) adeno-associated viral vectors of serotype 8 (AAV8) gene therapy targeting the liver prevents the development of obesity in initially lean mice by browning the large subcutaneous white adipose tissue (WAT) and enhancing energy expenditure. Here, we examine whether this approach could also reduce established obesity. Dietary-induced obese C57BL6/N mice received AAV8 BMP4 gene therapy at 17-18 weeks of age. They were kept on a high-fat diet and phenotypically characterized for an additional 10-12 weeks. Following termination, the mice underwent additional characterization in vitro. Surprisingly, we observed no effect on body weight, browning of WAT, or energy expenditure in these obese mice, but whole-body insulin sensitivity and glucose tolerance were robustly improved. Insulin signaling and insulin-stimulated glucose uptake were increased in both adipose cells and skeletal muscle. BMP4 also decreased hepatic glucose production and reduced gluconeogenic enzymes in the liver, but not in the kidney, in addition to enhancing insulin action in the liver. Our findings show that BMP4 prevents, but does not reverse, established obesity in adult mice, while it improves insulin sensitivity independent of weight reduction. The BMP antagonist Noggin was increased in WAT in obesity, which may account for the lack of browning
Differential branching fraction and angular analysis of the decay B0âKâ0ÎŒ+ÎŒâ
The angular distribution and differential branching fraction of the decay B 0â K â0 ÎŒ + ÎŒ â are studied using a data sample, collected by the LHCb experiment in pp collisions at sâ=7 TeV, corresponding to an integrated luminosity of 1.0 fbâ1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
Observation of excited Lambda_b0 baryons
Using pp collision data corresponding to 1.0 fb-1 integrated luminosity
collected by the LHCb detector, two narrow states are observed in the
Lambda_b0pi+pi- spectrum with masses 5911.97 +- 0.12(stat) +- 0.02(syst) +-
0.66(Lambda_b0 mass) MeV/c^2 and 5919.77 +- 0.08(stat) +- 0.02(syst) +-
0.66(Lambda_b0 mass) MeV/c^2. The significances of the observations are 5.2 and
10.2 standard deviations, respectively. These states are interpreted as the
orbitally-excited Lambda_b0 baryons, Lambda_b*0(5912) and Lambda_b*0(5920).Comment: Replaced by version published in Phys. Rev. Lett, modified fit with
better mass resolution treatmen
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
Strong constraints on the rare decays Bs -> mu+ mu- and B0 -> mu+ mu-
A search for Bs -> mu+ mu- and B0 -> mu+ mu- decays is performed using 1.0
fb^-1 of pp collision data collected at \sqrt{s}=7 TeV with the LHCb experiment
at the Large Hadron Collider. For both decays the number of observed events is
consistent with expectation from background and Standard Model signal
predictions. Upper limits on the branching fractions are determined to be BR(Bs
-> mu+ mu-) mu+ mu-) < 1.0 (0.81) x 10^-9 at
95% (90%) confidence level.Comment: 2+6 pages; 4 figures; Accepted for publication in Physical Review
Letter
Measurements of the branching fractions of B+âppK+ decays
The branching fractions of the decay B+ â ppÌK+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component MppÌ < 2.85 GeV/c2 and the branching fractions via the resonant ccÌ states η c(1S) and Ï(2S) relative to the decay via a J/Ï intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained
Search for the decay Bs0âD*âϱ
A search for the decay Bs0âD*âϱ is presented using a data sample corresponding to an integrated luminosity of 1.0ââfb-1 of pp collisions collected by LHCb. This decay is expected to be mediated by a W-exchange diagram, with little contribution from rescattering processes, and therefore a measurement of the branching fraction will help us to understand the mechanism behind related decays such as Bs0âÏ+Ï- and Bs0âDD- . Systematic uncertainties are minimized by using B0âD*âϱ as a normalization channel. We find no evidence for a signal, and set an upper limit on the branching fraction of B(Bs0âD*âϱ)<6.1(7.8)Ă10-6 at 90% (95%) confidence level
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
Measurements of the , , meson and baryon lifetimes
Measurements of -hadron lifetimes are reported using collision data,
corresponding to an integrated luminosity of 1.0fb, collected by the
LHCb detector at a centre-of-mass energy of Tev. Using the exclusive decays
, , ,
and the average decay
times in these modes are measured to be = 0.004 0.003 ps, =
0.006 0.004 ps, = 0.013
0.005 ps, = 0.027
0.006 ps and = 0.011
0.005 ps, where the first uncertainty is statistical and the second is
systematic. These represent the most precise lifetime measurements in these
decay modes. In addition, ratios of these lifetimes, and the ratio of the
decay-width difference, , to the average width, , in
the system, , are
reported. All quantities are found to be consistent with Standard Model
expectations.Comment: 28 pages, 4 figures. Updated reference
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