2,430 research outputs found
Infrapatellar fat pad adipose-derived stem cells co-cultured with articular chondrocytes from osteoarthritis patients exhibit increased chondrogenic gene expression.
AIM: The variable results in clinical trials of adipose tissue-derived stem cells (ASCs) for chondral defects may be due to the different ex vivo culture conditions of the ASCs which are implanted to treat the lesions. We sought to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression in a novel co-culture combination. METHODS: In our study, we utilized an in vitro autologous co-culture of IFPD ASCs and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic human knee joints at ASC-to-chondrocyte seeding log ratios of 1:1, 10:1, and 100:1. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenic gene expression. RESULTS: The chondrogenic gene expression profiles from co-cultures were greater than would be expected from an expression profile modeled from chondrocyte and ASC-only monocultures. Additionally, chondrogenic gene expression decreased with increasing ASC-to-chondrocyte seeding ratios. CONCLUSIONS: These findings provide insight into the mechanisms underlying clinical ASC therapies and signifies that IFPD ASCs pre-conditioned by chondrocyte co-culture may have improved chondrogenic potential for cartilage repair. This model can help further understand IFPD ASCs in chondral and osteochondral repair and the chondrogenic pathways involved. Video Abstract
Spin-Orbit-Induced Orbital Excitations in Sr2RuO4 and Ca2RuO4: A Resonant Inelastic X-ray Scattering Study
High-resolution resonant inelastic X-ray scattering (RIXS) at the oxygen
K-edge has been used to study the orbital excitations of Ca2RuO4 and Sr2RuO4.
In combination with linear dichroism X-ray absorption spectroscopy, the
ruthenium 4d-orbital occupation and excitations were probed through their
hybridization with the oxygen p-orbitals. These results are described within a
minimal model, taking into account crystal field splitting and a spin-orbit
coupling \lambda_{so}=200~meV. The effects of spin-orbit interaction on the
electronic structure and implications for the Mott and superconducting ground
states of (Ca,Sr)2RuO4 are discussed.Comment: accepted in PRB 201
Rare earth contributions to the X-ray magnetic circular dichroism at the Co K edge in rare earth-cobalt compounds investigated by multiple-scattering calculations
The X-ray magnetic circular dichroism (XMCD) has been measured at the Co K
edge in Co-hcp and R-Co compounds (R=La, Tb, Dy). The structure of the
experimental XMCD spectra in the near-edge region has been observed to be
highly sensitive to the magnetic environment of the absorbing site.
Calculations of the XMCD have been carried out at the Co K edge in Co metal,
LaCo and TbCo within the multiple-scattering framework including the
spin-orbit coupling. In the three systems, the XMCD spectra in the near-edge
region are well reproduced. The possibility to separate and quantitatively
estimate the local effects from those due to the neighboring atoms in the XMCD
cross section makes possible a more physical understanding of the spectra. The
present results emphasize the major role played by the states of the Tb
ions in the XMCD spectrum at the Co K edge in the TbCo compound.Comment: 34 pages, revtex, 10 eps figures included with epsf, after referee
revie
Quantum oscillations in quasi-one-dimensional metals with spin-density-wave ground states
We consider the magnetoresistance oscillation phenomena in the Bechgaard salts (TMTSF)(2)X, where X = ClO4, PF6, and AsF6 in pulsed magnetic fields to 51 T. Of particular importance is the observation of a new magnetoresistance oscillation for X = ClO4 in its quenched state. In the absence of any Fermi-surface reconstruction due to anion order at low temperatures, all three materials exhibit nonmonotonic temperature dependence of the oscillation amplitude in the spin-density-wave (SDW) state. We discuss a model where, below a characteristic temperature T* within the SDW state, a magnetic breakdown gap opens. [S0163-1829(99)00904-2]
Magnetic topology of active regions and coronal holes: implications for coronal outflows and the solar wind
During 2-18 January 2008 a pair of low-latitude opposite-polarity coronal holes (CHs) were observed on the Sun with two active regions (ARs) and the heliospheric plasma sheet located between them. We use the Hinode/EUV Imaging Spectrometer (EIS) to locate AR-related outflows and measure their velocities. Solar-Terrestrial Relations Observatory (STEREO) imaging is also employed, as are the Advanced Composition Explorer (ACE) in-situ observations, to assess the resulting impacts on the solar wind (SW) properties. Magnetic-field extrapolations of the two ARs confirm that AR plasma outflows observed with EIS are co-spatial with quasi-separatrix layer locations, including the separatrix of a null point. Global potential-field source-surface modeling indicates that field lines in the vicinity of the null point extend up to the source surface, enabling a part of the EIS plasma upflows access to the SW. We find that similar upflow properties are also observed within closed-field regions that do not reach the source surface. We conclude that some of plasma upflows observed with EIS remain confined along closed coronal loops, but that a fraction of the plasma may be released into the slow SW. This suggests that ARs bordering coronal holes can contribute to the slow SW. Analyzing the in-situ data, we propose that the type of slow SW present depends on whether the AR is fully or partially enclosed by an overlying streamer. © 2012 Springer Science+Business Media B.V
SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1
BACKGROUND
We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown.
METHODS
A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer.
RESULTS
Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53.
CONCLUSION
Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity
Urinary Extracellular Domain of Neurotrophin Receptor p75 as a Biomarker for Amyotrophic Lateral Sclerosis in a Chinese cohort
To comprehensively assess whether p75ECD in urine could be a candidate biomarker for ALS evaluation. Urine samples were collected from 101 ALS patients, 108 patients with other neurological disease (OND) and 97 healthy controls. 61 ALS patients were followed up with clinical data including ALSFRS-r every 6 to 12 months, 23 ALS patients died and 17 ALS patients lost touch during follow up period. Enzyme-linked immunoassay was employed to determine urine p75ECD concentration. The ALSFRS-r was employed to assess the severity of ALS. The concentration of p75ECD in ALS was significantly higher than that of OND and CTRL (p < 0.001). Additionally, urine p75ECD concentrations in ALS-definite grade patients were significantly higher than that in ALS-probable grade and ALS-possible grade patients (p < 0.001). Higher urine p75ECD concentrations were correlated with increased clinical stage (p = 0.0309); urine p75ECD concentrations and ALSFRS-r were negatively correlated (p = 0.022); and urine p75ECD concentration in the fast-progressing ALS group was significantly higher than that in slow-progression (p = 0.0026). Our finding indicates that urine p75ECD concentration provides additional evidence for patients with clinically suspected ALS, and can be employed to evaluate ALS-severity
Protocol for Physiotherapy OR Tvt Randomised Efficacy Trial (PORTRET): a multicentre randomised controlled trial to assess the cost-effectiveness of the tension free vaginal tape versus pelvic floor muscle training in women with symptomatic moderate to severe stress urinary incontinence
<p>Abstract</p> <p>Background</p> <p>Stress urinary incontinence is a common condition affecting approximately 20% of adult women causing substantial individual (quality of life) and economic (119 million Euro/year spent on incontinence pads in the Netherlands) burden. Pelvic floor muscle training (PFMT) is regarded as first line treatment, but only 15-25% of women will be completely cured. Approximately 65% will report that their condition improved, but long term adherence to treatment is problematic. In addition, at longer term (2-15 years) follow-up 30-50% of patients will end up having surgery. From 1996 a minimal invasive surgical procedure, the Tension-free Vaginal Tape (TVT) has rapidly become the gold standard in surgical treatment of stress urinary incontinence. With TVT 65-95% of women are cured. However, approximately 3-6% of women will develop symptoms of an overactive bladder, resulting in reduced quality of life. Because of its efficacy the TVT appears to be preferable over PFMT but both treatments and their costs have not been compared head-to-head in a randomised clinical trial.</p> <p>Methods/Design</p> <p>A multi-centre randomised controlled trial will be performed for women between 35 - 80 years old with moderate to severe, predominantly stress, urinary incontinence, who have not received specialised PFMT or previous anti-incontinence surgery. Women will be assigned to either PFMT by a specialised physiotherapist for a standard of 9-18 session in a period of 6 months, or TVT(O) surgery. The main endpoint of the study is the subjective improvement of urinary incontinence. As secondary outcome the objective cure will be assessed from history and clinical parameters. Subjective improvement in quality of life will be measured by generic (EQ-5D) and disease-specific (Urinary Distress Inventory and Incontinence Impact Questionnaire) quality of life instruments. The economical endpoint is short term (1 year) incremental cost-effectiveness in terms of costs per additional year free of urinary incontinence and costs per Quality Adjusted Life Years (QALY) gained. Finally, treatment strategy and patient characteristics will be combined in a prediction model, to allow for individual treatment decisions in future patients. Four hundred female patients will be recruited from over 30 hospitals in the Netherlands</p> <p>Trial registration</p> <p>Nederlands trial register: NTR 1248</p
Examining leptogenesis with lepton flavor violation and the dark matter abundance
Within a supersymmetric (SUSY) type-I seesaw framework with flavor-blind
universal boundary conditions, we study the consequences of requiring that the
observed baryon asymmetry of the Universe be explained by either thermal or
non-thermal leptogenesis. In the former case, we find that the parameter space
is very constrained. In the bulk and stop-coannihilation regions of mSUGRA
parameter space (that are consistent with the measured dark matter abundance),
lepton flavor-violating (LFV) processes are accessible at MEG and future
experiments. However, the very high reheat temperature of the Universe needed
after inflation (of about 10^{12} GeV) leads to a severe gravitino problem,
which disfavors either thermal leptogenesis or neutralino dark matter.
Non-thermal leptogenesis in the preheating phase from SUSY flat directions
relaxes the gravitino problem by lowering the required reheat temperature. The
baryon asymmetry can then be explained while preserving neutralino dark matter,
and for the bulk or stop-coannihilation regions LFV processes should be
observed in current or future experiments.Comment: 20 pages, 5 figures, 1 tabl
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