Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p\u3c0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure

Cx43 and mechanotransduction in bone

Bone adaptation to changes in mechanical stimuli occurs by adjusting bone formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone mass. Osteocytes coordinate the actions of these cells on the bone surface by sensing mechanical forces and producing cytokines that increase or prevent osteoblast and osteoclast differentiation and function. Channels formed by connexins (Cxs) and, in particular, connexin 43 (Cx43) in osteoblasts and osteocytes are central part of this mechanism to control bone mass. Cx43 hemichannels are opened by fluid flow and mediate the anti-apoptotic effect of mechanical stimulation in vitro, suggesting that Cx43 participates in mechanotransduction. However, mice lacking Cx43 in osteoblasts and/or osteocytes show an increased anabolic response to loading and decreased catabolic response to unloading. This evidence suggests that Cx43 channels expressed in osteoblastic cells are not required for the response to mechanical stimulation, but mediate the consequence of lack thereof. The molecular basis of these unexpected responses to mechanical stimulation is currently under investigation

Nanotopographic Cell Culture Substrate: Polymer-Demixed Nanotextured Films Under Cell Culture Conditions

Modulating physical cell culture environments via nanoscale substrate topographic modification has recently been of significant interest in regenerative medicine. Many studies have utilized a polymer-demixing technique to produce nanotextured films and showed that cellular adhesion, proliferation, and differentiation could be regulated by the shape and scale of the polymer-demixed nanotopographies. However, little attention has been paid to the topographic fidelity of the polymer-demixed films when exposed to cell culture conditions. In this brief article, two polymer-demixing systems were employed to assess topographic changes in polymer-demixed films after fibronectin (FN) extracellular matrix protein adsorption and after incubation in phosphate-buffered saline at 37◦C. We showed that FN adsorption induced very small variations ( \u3c 2 nm) to the polystyrene/polybromostyrene (PS/PBrS)-demixed nanoisland textures, not substantially altering the nanotopographies given by the polymer demixing. In addition, poly(L-lactic acid)/PS (PLLA/PS)-demixed nanoisland topographies using PLLA with Mw = 50 x 103 did not show notable degradation up to day 24

No planet for HD 166435

The G0V star HD166435 has been observed by the fiber-fed spectrograph ELODIE as one of the targets in the large extra-solar planet survey that we are conducting at the Observatory of Haute-Provence. We detected coherent, low-amplitude, radial-velocity variations with a period of 3.7987days, suggesting a possible close-in planetary companion. Subsequently, we initiated a series of high-precision photometric observations to search for possible planetary transits and an additional series of CaII H and K observations to measure the level of surface magnetic activity and to look for possible rotational modulation. Surprisingly, we found the star to be photometrically variable and magnetically active. A detailed study of the phase stability of the radial-velocity signal revealed that the radial-velocity variability remains coherent only for durations of about 30days. Analysis of the time variation of the spectroscopic line profiles using line bisectors revealed a correlation between radial velocity and line-bisector orientation. All of these observations, along with a one-quarter cycle phase shift between the photometric and the radial-velocity variationss, are well explained by the presence of dark photospheric spots on HD166435. We conclude that the radial-velocity variations are not due to gravitational interaction with an orbiting planet but, instead, originate from line-profile changes stemming from star spots on the surface of the star. The quasi-coherence of the radial-velocity signal over more than two years, which allowed a fair fit with a binary model, makes the stability of this star unusual among other active stars. It suggests a stable magnetic field orientation where spots are always generated at about the same location on the surface of the star.Comment: 9 pages, 8 figures, Accepted for publication in A&

Constraints on Primordial Nongaussiantiy from the High-Redshift Cluster MS1054--03

The implications of the massive, X-ray selected cluster of galaxies MS1054--03 at $z=0.83$ are discussed in light of the hypothesis that the primordial density fluctuations may be nongaussian. We generalize the Press-Schechter (PS) formalism to the nongaussian case, and calculate the likelihood that a cluster as massive as MS1054 would appear in the EMSS. The probability of finding an MS1054-like cluster depends only on \omegam and the extent of primordial nongaussianity. We quantify the latter by adopting a specific functional form for the PDF, denoted $\psi_\lambda,$ which tends to Gaussianity for $\lambda\gg 1,$ and show how $\lambda$ is related to the more familiar statistic $T,$ the probability of $\ge 3\sigma$ fluctuations for a given PDF relative to a Gaussian. We find that Gaussian initial density fluctuations are consistent with the data on MS1054 only if \omegam\simlt 0.2. For \omegam\ge 0.25 a significant degree of nongaussianity is required, unless the mass of MS1054 has been substantially overestimated by X-ray and weak lensing data. The required amount of nongaussianity is a rapidly increasing function of \omegam for 0.25 \le \omegam \le 0.45, with $\lambda \le 1$ (T \simgt 7) at the upper end of this range. For a fiducial \omegam=0.3, \omegal=0.7 universe, favored by several lines of evidence we obtain an upper limit $\lambda \le 10,$ corresponding to a $T\ge 3.$ This finding is consistent with the conclusions of Koyama, Soda, & Taruya (1999), who applied the generalized PS formalism to low (z\simlt 0.1) and intermediate (z\simlt 0.6) redshift cluster data sets.Comment: 15 pages, 11 figures, submitted to the Astrophysical Journal, uses emulateapj.st

YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK

While yes-associated protein (YAP) is now recognized as a potent mechanosensitive transcriptional regulator to affect cell growth and differentiation including the osteogenic transcription of mesenchymal stem cells (MSCs), most studies have reported the YAP mechanosensing of static mechanophysical cues such as substrate stiffness. We tested MSC response to dynamic loading, i.e., cyclic mechanical stretching, and assessed YAP mechanosensing and resultant MSC osteogenesis. We showed that cyclic stretching at 10% strain and 1 Hz frequency triggered YAP nuclear import in MSCs. YAP phosphorylation at S127 and S397, which is required for YAP cytoplasmic retention, was suppressed by cyclic stretch. We also observed that anti-YAP-regulatory Hippo pathway, LATS phosphorylation, was significantly decreased by stretch. We confirmed the stretch induction of MSC osteogenic transcription and differentiation, and this was impaired under YAP siRNA suggesting a key role of YAP dynamic mechanosensing in MSC osteogenesis. As an underlying mechanism, we showed that the YAP nuclear transport by cyclic stretch was abrogated by ROCK inhibitor, Y27632. ROCK inhibitor also impaired the stretch induction of F-actin formation and MSC osteogenesis, thus implicating the role of the ROCK-F-actin cascade in stretch-YAP dynamic mechanosensing-MSC osteogenesis. Our results provide insight into bone tissue engineering and skeletal regenerative capacity of MSCs especially as regards the role of dynamic mechanical loading control of YAPmediated MSC osteogenic transcription

Coronal activity cycles in nearby G and K stars - XMM-Newton monitoring of 61 Cygni and Alpha Centauri

We use X-ray observations of the nearby binaries 61 Cyg A/B (K5V and K7V) and Alpha Cen A/B (G2V and K1V) to study the long-term evolution of magnetic activity in weakly to moderately active G + K dwarfs over nearly a decade. Specifically we search for X-ray activity cycles and related coronal changes and compare them to the solar behavior. For 61 Cyg A we find a regular coronal activity cycle analog to its 7.3 yr chromospheric cycle. The X-ray brightness variations are with a factor of three significantly lower than on the Sun, yet the changes of coronal properties resemble the solar behavior with larger variations occurring in the respective hotter plasma components. 61 Cyg B does not show a clear cyclic coronal trend so far, but the X-ray data matches the more irregular chromospheric cycle. Both Alpha Cen stars exhibit significant long-term X-ray variability. Alpha Cen A shows indications for cyclic variability of an order of magnitude with a period of about 12-15 years; the Alpha Cen B data suggests an X-ray cycle with an amplitude of about six to eight and a period of 8-9 years. The sample stars exhibit X-ray luminosities ranging between Lx < 1x10^26 - 3x10^27 erg s^-1 in the 0.2-2.0 keV band and have coronae dominated by cool plasma with variable average temperatures of around 1.0-2.5 MK. We find that coronal activity cycles are apparently a common phenomenon in older, slowly rotating G and K stars. The spectral changes of the coronal X-ray emission over the cycles are solar-like in all studied targets.Comment: 11 pages, 9 figures, accepted by Astronomy and Astrophysic

NoSOCS in SDSS. II. Mass Calibration of Low Redshift Galaxy Clusters with Optical and X-ray Properties

We use SDSS data to investigate the scaling relations of 127 NoSOCS and 56 CIRS galaxy clusters at low redshift ($z \le 0.10$). We show that richness and both optical and X-ray luminosities are reliable mass proxies. The scatter in mass at fixed observable is $\sim$ 40%, depending on the aperture, sample and observable considered. For example, for the massive CIRS systems $\sigma_{lnM500|N500}$ = 0.33 $\pm$ 0.05 and $\sigma_{lnM500|Lx}$ = 0.48 $\pm$ 0.06. For the full sample $\sigma_{lnM500|N500}$ = 0.43 $\pm$ 0.03 and $\sigma_{lnM500|Lx}$ = 0.56 $\pm$ 0.06. We estimate substructure using two and three dimensional optical data, verifying that substructure has no significant effect on the cluster scaling relations (intercepts and slopes), independent of which substructure test we use. For a subset of twenty-one clusters, we estimate masses from the M-T$_X$ relation using temperature measures from BAX. The scaling relations derived from the optical and X-ray masses are indeed very similar, indicating that our method consistently estimates the cluster mass and yields equivalent results regardless of the wavelength from which we measure mass. For massive systems, we represent the mass-richness relation by a function with the form ${\rm ln (M_{200}) = A + B \times ln(N_{200}/60)}$, with M$_{200}$ being expressed in units of 10$^{14}$ M$_{\odot}$. Using the virial mass, for CIRS clusters, we find A = (1.39 $\pm$ 0.07) and B = (1.00 $\pm$ 0.11). The relations based on the virial mass have a scatter of $\sigma_{lnM200|N200}$ = 0.37 $\pm$ 0.05, while $\sigma_{lnM200|N200}$ = 0.77 $\pm$ 0.22 for the caustic mass and $\sigma_{lnM200|N200}$ = 0.34 $\pm$ 0.08 for the temperature based mass (abridged).Comment: 27 pages, 22 figures, 12 tables, Accepted to MNRA

Chandra detection of the intracluster medium around 3C294 at z=1.786

We present a Chandra observation of the powerful radio galaxy 3C294 showing clear evidence for a surrounding intracluster medium. At a redshift of 1.786 this is the most distant cluster of galaxies yet detected in X-rays. The radio core is detected as a point source, which has a spectrum consistent with a heavily-absorbed power law implying an intrinsic 2-10 keV luminosity of ~10^45 erg/s. A small excess of emission is associated with the southern radio hotspots. The soft, diffuse emission from the intracluster medium is centred on the radio source. It has an hour-glass shape in the N-S direction, extending to radii of at least 100 kpc, well beyond the radio source. The X-ray spectrum of this extended component is fit by a thermal model with temperature ~5 keV, or by gas cooling from above 7 keV at rates of ~400-700 Msolar/yr. The rest-frame 0.3-10 keV luminosity of the cluster is ~4.5x10^44 erg/s. The existence of such a cluster is consistent with a low density universe.Comment: 5 pages, 6 figures, accepted by MNRA

Mg II h + k emission lines as stellar activity indicators of main sequence F-K stars

The main purpose of this study is to use the IUE spectra in the analysis of magnetic activity of main sequence F-K stars. Combining IUE observations of MgII and optical spectroscopy of Ca II, the registry of ctivity of stars can be extended in time. We retrieved all the high-resolution spectra of F, G, and K main sequence stars observed by IUE (i.e. 1623 spectra of 259 F to K dwarf stars). We obtained the continuum surface flux near the Mg II h+k lines near 2800 \AA and the MgII line-core surface flux from the IUE spectra. We obtained a relation between the mean continuum flux near the MgII lines with the colour $B-V$ of the star. For a set of 117 nearly simultaneous observations of Mg II and Ca II fluxes of 21 F5 to K3 main sequence stars, we obtained a colour dependent relation between the Mount Wilson CaII S-index and the MgII emission line-core flux. As an application of this calibration, we computed the Mount Wilson index for all the dF to dK stars which have high resolution IUE spectra. For some of the most frequently observed main sequence stars, we analysed the Mount Wilson index S from the IUE spectra, together with the ones derived from visible spectra. We confirm the cyclic chromospheric activity of epsilon Eri (HD 22049) and beta Hydri (HD 2151), and we find a magnetic cycle in alpha Cen B (HD 128621). Complete abstract in the paper.Comment: 10 pages, accepted for publication in Astronomy and Astrophysic