4,422 research outputs found
MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.
Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor-MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet-induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases
Congenital bipartite lunate presenting as a misdiagnosed lunate fracture: a case report
<p>Abstract</p> <p>Introduction</p> <p>A rare case of congenital bipartite lunate in a child is reported. Carpal variants are very uncommon as independent entities, with only three previous reports of this condition in the English literature.</p> <p>Case presentation</p> <p>An 11-year-old Caucasian boy presented with pain in the left wrist after a fall. Radiographs in the emergency department demonstrated a lunate that was divided into palmar and dorsal parts, causing a misdiagnosis of fractured lunate. Magnetic resonance imaging was then used to differentiate between the two diagnoses.</p> <p>Conclusion</p> <p>Very few cases of bipartite lunate have been reported in the literature, and unless awareness is raised about congenital anomalies such as this variant, confusion may arise.</p
Accumulation of uPA – PAI-1 complexes inside the tumour cells is associated with axillary nodal invasion in progesterone-receptor-positive early breast cancer
Vortex State and Field-Angle Resolved Specific Heat Oscillation for H // ab in d-Wave Superconductors
When magnetic field is applied parallel to the ab plane in d_{x^2-y^2}-wave
superconductors, the transition of stable vortex lattice structure, spatial
structure of local density of states, and specific heat oscillation by rotation
of magnetic field orientation are investigated by quantitative calculations
based on the selfconsistent Eilenberger theory. We estimate how the vortex
state changes depending on the relative angle between the node-direction of the
superconducting gap and magnetic field orientation. To reproduce the
sign-change of specific heat oscillation observed in CeCoIn_5, our study is
done by including strong paramagnetic effect. The quantitative theoretical
calculations give decisive information to analyze the experimental data on the
field-angle dependence, and establish the angle-resolved specific heat
experiment as a spectroscopic means to identify the node-position of the
superconducting gap.Comment: 9 pages, 13 figure
Solar-type dynamo behaviour in fully convective stars without a tachocline
In solar-type stars (with radiative cores and convective envelopes), the
magnetic field powers star spots, flares and other solar phenomena, as well as
chromospheric and coronal emission at ultraviolet to X-ray wavelengths. The
dynamo responsible for generating the field depends on the shearing of internal
magnetic fields by differential rotation. The shearing has long been thought to
take place in a boundary layer known as the tachocline between the radiative
core and the convective envelope. Fully convective stars do not have a
tachocline and their dynamo mechanism is expected to be very different,
although its exact form and physical dependencies are not known. Here we report
observations of four fully convective stars whose X-ray emission correlates
with their rotation periods in the same way as in Sun-like stars. As the X-ray
activity - rotation relationship is a well-established proxy for the behaviour
of the magnetic dynamo, these results imply that fully convective stars also
operate a solar-type dynamo. The lack of a tachocline in fully convective stars
therefore suggests that this is not a critical ingredient in the solar dynamo
and supports models in which the dynamo originates throughout the convection
zone.Comment: 6 pages, 1 figure. Accepted for publication in Nature (28 July 2016).
Author's version, including Method
Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling
Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio
Ligand binding site superposition and comparison based on Atomic Property Fields: identification of distant homologues, convergent evolution and PDB-wide clustering of binding sites
A new binding site comparison algorithm using optimal superposition of the continuous pharmacophoric property distributions is reported. The method demonstrates high sensitivity in discovering both, distantly homologous and convergent binding sites. Good quality of superposition is also observed on multiple examples. Using the new approach, a measure of site similarity is derived and applied to clustering of ligand binding pockets in PDB
Whole Body Mechanics of Stealthy Walking in Cats
The metabolic cost associated with locomotion represents a significant part of an animal's metabolic energy budget. Therefore understanding the ways in which animals manage the energy required for locomotion by controlling muscular effort is critical to understanding limb design and the evolution of locomotor behavior. The assumption that energetic economy is the most important target of natural selection underlies many analyses of steady animal locomotion, leading to the prediction that animals will choose gaits and postures that maximize energetic efficiency. Many quadrupedal animals, particularly those that specialize in long distance steady locomotion, do in fact reduce the muscular contribution required for walking by adopting pendulum-like center of mass movements that facilitate exchange between kinetic energy (KE) and potential energy (PE) [1]–[4]. However, animals that are not specialized for long distance steady locomotion may face a more complex set of requirements, some of which may conflict with the efficient exchange of mechanical energy. For example, the “stealthy” walking style of cats may demand slow movements performed with the center of mass close to the ground. Force plate and video data show that domestic cats (Felis catus, Linnaeus, 1758) have lower mechanical energy recovery than mammals specialized for distance. A strong negative correlation was found between mechanical energy recovery and diagonality in the footfalls and there was also a negative correlation between limb compression and diagonality of footfalls such that more crouched postures tended to have greater diagonality. These data show a previously unrecognized mechanical relationship in which crouched postures are associated with changes in footfall pattern which are in turn related to reduced mechanical energy recovery. Low energy recovery was not associated with decreased vertical oscillations of the center of mass as theoretically predicted, but rather with posture and footfall pattern on the phase relationship between potential and kinetic energy. An important implication of these results is the possibility of a tradeoff between stealthy walking and economy of locomotion. This potential tradeoff highlights the complex and conflicting pressures that may govern the locomotor choices that animals make
The siRNA targeted to mdr1b and mdr1a mRNAs in vivo sensitizes murine lymphosarcoma to chemotherapy
Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+
The COMPASS experiment at the CERN SPS has studied the diffractive
dissociation of negative pions into the pi- pi- pi+ final state using a 190
GeV/c pion beam hitting a lead target. A partial wave analysis has been
performed on a sample of 420000 events taken at values of the squared
4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances
a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data
show a significant natural parity exchange production of a resonance with
spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The
resonant nature of this wave is evident from the mass-dependent phase
differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a
resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2
is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged;
version 3 updated authors, text shortened, data unchange
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