Interfering with TGFβ-induced Smad3 nuclear accumulation differentially affects TGFβ-dependent gene expression

BACKGROUND: Transforming growth factor-β (TGFβ) plays an important role in late-stage carcinogenesis by stimulating invasive behavior of cancer cells, promoting neo-angiogenesis and by helping cancer cells to escape surveillance by the immune system. It also supports colonization of the bone by metastatic breast cancer cells by increasing expression of osteolytic parathyroid hormone-related protein (PTHrP). Interfering with TGFβ signalling may thus weaken the malignant properties of cancer cells. We investigated to what extent two inhibitors, SB-202190 and SB-203580, interfere with TGFβ-signalling in invasive MDA-MB-231 breast cancer cells. These compounds, formerly used as p38-MAPK-specific inhibitors, were recently also demonstrated to inhibit TGFβ type I receptor kinase. RESULTS: Our results show that these inhibitors delay the onset of TGFβ-induced nuclear accumulation of Smad3 and reduces its amplitude. This effect was accompanied by a strong reduction in TGFβ-responsivess of the slow-responder genes pthrp, pai-1 and upa, while the reactivity of the fast-responder gene smad7 to TGFβ remained almost unchanged. Neither was the TGFβ response of the fast-responder ese-1/esx gene, whose expression we found to be strongly downregulated by TGFβ, affected by the inhibitors. CONCLUSION: The data show that SB-202190 and SB-203580 suppress TGFβ-dependent activation of genes that are important for the acquisition of invasive behavior, while having no effect on the expression of the natural TGFβ inhibitor Smad7. This suggests that these compounds are potent inhibitors of malignant behavior of cancer cells

Huge enhancement of electronmechanical responses in compositionally modulated PZT

Monte Carlo simulations based on a first-principles-derived Hamiltonian are conducted to study the properties of PZT alloys compositionally modulated along the [100] pseudocubic direction near the morphotropic phase boundary (MPB). It is shown that compositional modulation causes the polarization to continuously rotate away from the modulation direction, resulting in the unusual triclinic and C-type monoclinic ground states and huge enhancement of electromechanical responses (the peak of piezoelectric coefficient is as high as 30000 pC/N). The orientation dependence of dipole-dipole interaction in modulated structure is revealed as the microscopic mechanism to be responsible for these anomalies.Comment: 5 pages, 4 figure

Superconductivity and crystalline electric field effects in the filled skutterudite series Pr(Os1−x_{1-x}Rux_x)4_4Sb12_{12}

X-ray powder diffraction, magnetic susceptibility $\chi(T)$, and electrical resistivity $\rho(T)$ measurements were made on single crystals of the filled skutterudite series Pr(Os$_{1-x}$Ru$_x$)$_4$Sb$_{12}$. One end of the series ($x = 0$) is a heavy fermion superconductor with a superconducting critical temperature $T_{c} = 1.85$ K, while the other end ($x = 1$) is a conventional superconductor with $T_{c} \approx 1$ K. The lattice constant $a$ decreases approximately linearly with increasing Ru concentration $x$. As Ru (Os) is substituted for Os (Ru), $T_{c}$ decreases nearly linearly with substituent concentration and exhibits a minimum with a value of $T_{c} = 0.75$ K at $x = 0.6$, suggesting that the two types of superconductivity compete with one another. Crystalline electric field (CEF) effects in $\chi_\mathrm{dc}(T)$ and $\rho(T)$ due to the splitting of the Pr$^{3+}$ nine-fold degenerate Hund's rule $J = 4$ multiplet are observed throughout the series, with the splitting between the ground state and the first excited state increasing monotonically as $x$ increases. The fits to the $\chi_\mathrm{dc}(T)$ and $\rho(T)$ data are consistent with a $\Gamma_{3}$ doublet ground state for all values of x, although reasonable fits can be obtained for a $\Gamma_{1}$ ground state for $x$ values near the end member compounds ($x = 0$ or $x = 1$).Comment: 10 pages, 8 figures, submitted to Phys. Rev.

Space-time versus particle-hole symmetry in quantum Enskog equations

The non-local scattering-in and -out integrals of the Enskog equation have reversed displacements of colliding particles reflecting that the -in and -out processes are conjugated by the space and time inversions. Generalisations of the Enskog equation to Fermi liquid systems are hindered by a request of the particle-hole symmetry which contradicts the reversed displacements. We resolve this problem with the help of the optical theorem. It is found that space-time and particle-hole symmetry can only be fulfilled simultaneously for the Bruckner-type of internal Pauli-blocking while the Feynman-Galitskii form allows only for particle-hole symmetry but not for space-time symmetry due to a stimulated emission of Bosons

Kinetic Properties of a Bose-Einstein Gas at Finite Temperature

We study, in the framework of the Boltzmann-Nordheim equation (BNE), the kinetic properties of a boson gas above the Bose-Einstein transition temperature $T_c$. The BNE is solved numerically within a new algorithm, that has been tested with exact analytical results for the collision rate of an homogeneous system in thermal equilibrium. In the classical regime ($T > 6~ T_c$), the relaxation time of a quadrupolar deformation in momentum space is proportional to the mean free collision time $\tau_{relax} \sim T^{-1/2}$. Approaching the critical temperature ($T_c < T < 2.7~ T_c$), quantum statistic effects in BNE become dominant, and the collision rate increases dramatically. Nevertheless, this does not affect the relaxation properties of the gas that depend only on the spontaneous collision term in BNE. The relaxation time $\tau_{relax}$ is proportional to $(T - T_c)^{-1/2}$, exhibiting a critical slowing down. These phenomena can be experimentally confirmed looking at the damping properties of collective motions induced on trapped atoms. The possibility to observe a transition from collisionless (zero-sound) to hydrodynamic (first-sound) is finally discussed.Comment: RevTeX, 5 figures. Submitted to Phys. Rev.

Observations of a Solar Energetic Particle Event From Inside and Outside the Coma of Comet 67P

Publisher Copyright: ©2022. The Authors.We analyze observations of a solar energetic particle (SEP) event at Rosetta's target comet 67P/Churyumov-Gerasimenko during 6–10 March 2015. The comet was 2.15 AU from the Sun, with the Rosetta spacecraft approximately 70 km from the nucleus placing it deep inside the comet's coma and allowing us to study its response. The Eastern flank of an interplanetary coronal mass ejection (ICME) also encountered Rosetta on 6 and 7 March. Rosetta Plasma Consortium data indicate increases in ionization rates, and cometary water group pickup ions exceeding 1 keV. Increased charge exchange reactions between solar wind ions and cometary neutrals also indicate increased upstream neutral populations consistent with enhanced SEP induced surface activity. In addition, the most intense parts of the event coincide with observations interpreted as an infant cometary bow shock, indicating that the SEPs may have enhanced the formation and/or intensified the observations. These solar transient events may also have pushed the cometopause closer to the nucleus. We track and discuss characteristics of the SEP event using remote observations by SOHO, WIND, and GOES at the Sun, in situ measurements at Solar Terrestrial Relations Observatory Ahead, Mars and Rosetta, and ENLIL modeling. Based on its relatively prolonged duration, gradual and anisotropic nature, and broad angular spread in the heliosphere, we determine the main particle acceleration source to be a distant ICME which emerged from the Sun on 6 March 2015 and was detected locally in the Martian ionosphere but was never encountered by 67P directly. The ICME's shock produced SEPs for several days which traveled to the in situ observation sites via magnetic field line connections.Peer reviewe

Is long-bout sedentary behaviour associated with long-term glucose levels 3 months after acute ischaemic stroke? A prospective observational cohort study

Background and purpose Sedentary behaviour is a risk factor for vascular disease and stroke patients are more sedentary than their age-matched peers. The association with glucose levels, as a potential mediator, is unclear, and we have investigated the association between long-bout sedentary behaviour and long-term glucose levels in stroke survivors. Methods This study uses data from the Norwegian Cognitive Impairment After Stroke study, a multicentre cohort study. The patients were recruited at hospital admission for acute stroke, and the follow-up was done at the outpatient clinic. Sedentary behaviour—being in a sitting or reclining position—was registered 3 months after stroke using position transition data from the body-worn sensor activPAL attached to the unaffected thigh. A MATLAB script was developed to extract activity data from 08:00 to 10:00 for 4 days and to categorise the data into four bout-length categories. The primary outcome was glycated haemoglobin (HbA1c), analysed at 3 months. Regression models were used to analyse the association between HbA1c and sedentary behaviour in the whole population and stratified based on a diagnosis of diabetes mellitus (DM). Age, body mass index and the use of antidiabetic drugs were added as covariates into the models. Results From a total of 815 included patients, 379 patients fulfilled the inclusion criteria for this study. We found no association between time in sedentary behaviour and HbA1c in the whole stroke population. We found time in sedentary behaviour in bouts of ≥90 min to be associated with a higher HbA1c in patients with DM. Conclusion Long-bout sedentary time is associated with a higher HbA1c in patients with DM 3 months after ischaemic stroke. Future research should investigate the benefit of breaking up sedentary time as a secondary preventive measure.publishedVersio

Detection of a strongly negative surface potential at Saturn's moon Hyperion

On 26 September 2005, Cassini conducted its only close targeted flyby of Saturn's small, irregularly shaped moon Hyperion. Approximately 6 min before the closest approach, the electron spectrometer (ELS), part of the Cassini Plasma Spectrometer (CAPS) detected a field-aligned electron population originating from the direction of the moon's surface. Plasma wave activity detected by the Radio and Plasma Wave instrument suggests electron beam activity. A dropout in energetic electrons was observed by both CAPS-ELS and the Magnetospheric Imaging Instrument Low-Energy Magnetospheric Measurement System, indicating that the moon and the spacecraft were magnetically connected when the field-aligned electron population was observed. We show that this constitutes a remote detection of a strongly negative (~ −200 V) surface potential on Hyperion, consistent with the predicted surface potential in regions near the solar terminator