Smad4 regulates growth plate matrix production and chondrocyte polarity.

Smad4 is an intracellular effector of the TGFβ family that has been implicated in Myhre syndrome, a skeletal dysplasia characterized by short stature, brachydactyly and stiff joints. The TGFβ pathway also plays a critical role in the development, organization and proliferation of the growth plate, although the exact mechanisms remain unclear. Skeletal phenotypes in Myhre syndrome overlap with processes regulated by the TGFβ pathway, including organization and proliferation of the growth plate and polarity of the chondrocyte. We used in vitro and in vivo models of Smad4 deficiency in chondrocytes to test the hypothesis that deregulated TGFβ signaling leads to aberrant extracellular matrix production and loss of chondrocyte polarity. Specifically, we evaluated growth plate chondrocyte polarity in tibiae of Col2-Cre+/-;Smad4fl/fl mice and in chondrocyte pellet cultures. In vitro and in vivo, Smad4 deficiency decreased aggrecan expression and increased MMP13 expression. Smad4 deficiency disrupted the balance of cartilage matrix synthesis and degradation, even though the sequential expression of growth plate chondrocyte markers was intact. Chondrocytes in Smad4-deficient growth plates also showed evidence of polarity defects, with impaired proliferation and ability to undergo the characteristic changes in shape, size and orientation as they differentiated from resting to hypertrophic chondrocytes. Therefore, we show that Smad4 controls chondrocyte proliferation, orientation, and hypertrophy and is important in regulating the extracellular matrix composition of the growth plate

Phonon and crystal field excitations in geometrically frustrated rare earth titanates

The phonon and crystal field excitations in several rare earth titanate pyrochlores are investigated. Magnetic measurements on single crystals of Gd2Ti2O7, Tb2Ti2O7, Dy2Ti2O7 and Ho2Ti2O7 are used for characterization, while Raman spectroscopy and terahertz time domain spectroscopy are employed to probe the excitations of the materials. The lattice excitations are found to be analogous across the compounds over the whole temperature range investigated (295-4 K). The resulting full phononic characterization of the R2Ti2O7 pyrochlore structure is then used to identify crystal field excitations observed in the materials. Several crystal field excitations have been observed in Tb2Ti2O7 in Raman spectroscopy for the first time, among which all of the previously reported excitations. The presence of additional crystal field excitations, however, suggests the presence of two inequivalent Tb3+ sites in the low temperature structure. Furthermore, the crystal field level at approximately 13 cm-1 is found to be both Raman and dipole active, indicating broken inversion symmetry in the system and thus undermining its current symmetry interpretation. In addition, evidence is found for a significant crystal field-phonon coupling in Tb2Ti2O7. These findings call for a careful reassessment of the low temperature structure of Tb2Ti2O7, which may serve to improve its theoretical understanding.Comment: 13 pages, 7 figure

Loss of α-Synuclein Does Not Affect Mitochondrial Bioenergetics in Rodent Neurons.

Increased α-synuclein (αsyn) and mitochondrial dysfunction play central roles in the pathogenesis of Parkinson's disease (PD), and lowering αsyn is under intensive investigation as a therapeutic strategy for PD. Increased αsyn levels disrupt mitochondria and impair respiration, while reduced αsyn protects against mitochondrial toxins, suggesting that interactions between αsyn and mitochondria influences the pathologic and physiologic functions of αsyn. However, we do not know if αsyn affects normal mitochondrial function or if lowering αsyn levels impacts bioenergetic function, especially at the nerve terminal where αsyn is enriched. To determine if αsyn is required for normal mitochondrial function in neurons, we comprehensively evaluated how lowering αsyn affects mitochondrial function. We found that αsyn knockout (KO) does not affect the respiration of cultured hippocampal neurons or cortical and dopaminergic synaptosomes, and that neither loss of αsyn nor all three (α, β and γ) syn isoforms decreased mitochondria-derived ATP levels at the synapse. Similarly, neither αsyn KO nor knockdown altered the capacity of synaptic mitochondria to meet the energy requirements of synaptic vesicle cycling or influenced the localization of mitochondria to dopamine (DA) synapses in vivo. Finally, αsyn KO did not affect overall energy metabolism in mice assessed with a Comprehensive Lab Animal Monitoring System. These studies suggest either that αsyn has little or no significant physiological effect on mitochondrial bioenergetic function, or that any such functions are fully compensated for when lost. These results implicate that αsyn levels can be reduced in neurons without impairing (or improving) mitochondrial bioenergetics or distribution

Observation of the algebraic localization-delocalization transition in a 1D disordered potential with a bias force

In a one-dimensional (1D) disordered potential, quantum interferences leading to Anderson lo-calization are ubiquitous, such that all wave-functions are exponentially localized. Moreover, no phase transition toward delocalization is expected in 1D. This behavior is strongly modified in the presence of a bias force. We experimentally study this case, launching a non-interacting 39 K Bose-Einstein condensate in a 1D disordered potential induced by a far-off-resonance laser speckle, while controlling a bias force. In agreement with theoretical predictions, we observe a transition between algebraic localization and delocalization as a function of our control parameter that is the relative strength of the disorder against the bias force. We also demonstrate that the initial velocity of the wave-packet only plays a role through an effective disorder strength due to the correlation of the disorder. Adding a bias force is a quite natural way to probe the transport properties of quantum systems, a subject of broad interest that can be in particular addressed with atomic quantum gases thanks to their high degree of control and versatility [1]. For example, Bloch oscillations has been measured through the addition of a constant force to atoms in periodic potential induced by an optical lattice [2]. A force applied to a harmonic trap is equivalent to a trap displacement. The response to such a displacement permits to reveal the fluid or insulating behavior of atomic systems. In 1D interacting Bose gases, the pinning transition by an optical lattice [3] or the insulating transition in quasi-disordered optical lattice [4, 5] have been studied in this manner. More recently, transport in quantum gases is also studied in junction-type setup more analogous to condensed-matter systems: two reservoirs with different chemical potentials are connected through a constriction. For example, in a gas of fermions, the quantization of conductance through a quantum point contact [6] and the superfluid to normal transition in a disordered thin film have been observed [7]. In our work, we focus on the transport of non-interacting particles in disordered media. Without a bias force, quantum interferences between multiple paths lead to Anderson localization [8] whose signature is an exponential decay in space of single particle wave-function [9]. This phenomenon is ubiquitous in wave/quantum physics and it has been observed in many physical contexts [10] including condensed-matter [11] and ultra-cold atoms [12-14]. One-dimensional truly disordered systems are always localized [15], contrary to the 3D case where a phase transition between localized and extended single particle wave-functions takes place as a function of the disorder strength [16-18]. The localization properties of 1D disordered systems are modified in the presence of a bias force. Theoretical studies predict a transition from algebraic localization to delocalization as a function of a single control non-dimensional parameter α which is the ratio of the force to the disorder strength [19, 20]. Physically, α is the relative energy gain ∆E/E of a particle of energy E when moving over a localization length. Interestingly, in a 1D white noise disorder, this quantity is independent of E as the localization length is proportional to E. If α is small, the force does not considerably change the localization behavior of the particle while for large α its dynamics is severely affected leading to delocalization. This localization-delocalization transition is predicted in the infinite time limit for white noise disorder [20]. In a correlated disorder, as the one produced from a far-off-resonance laser speckle [21], the situation is more complicated. Speckles have no Fourier component beyond a spatial frequency 2k c. As a consequence, back-scattering and localization are not expected in the framework of Born approximation for atoms with wavevectors k > k c [12, 22]. Since localized wave-functions always have a small fraction at long distance corresponding to large energies and momenta in the presence of a bias force, we thus expect correlation-induced delocalization at infinite time. However, signatures of the algebraic localization-delocalization transition are predicted to be observable at transient times [20]. In this paper, we report on the observation of the algebraic localization-delocalization transition with cold-atoms propagating in a one dimensional disordered potential in the presence of a controlled bias force. We experimentally show that the non-dimensional parameter α is the only relevant parameter to describe the transition. We notice that the initial velocity of the quantum wave packet only plays a role through the correlation of the disordered potential, showing that the transition is in-trinsically energy independent. In the localized regime, we demonstrate an algebraic decay of the density and measure the corresponding decay exponent as a function of α. At large disorder strength, a saturation of the exp

Insights from the shell proteome : Biomineralization to adaptation

Acknowledgments This work was supported by funding from the CACHE (Calcium in a Changing Environment) initial training network (ITN) under the European Union Seventh Framework Programme, reference grant agreement number 605051. We acknowledge E. Dufour (UMR 7209, MNHN) for shell sample preparation. We thank G. Bolbach and L. Matheron (IBPS-FR3631, Paris) for proteomic analysis and discussionsPeer reviewedPublisher PD

Beyond production and consumption: using throughflows to untangle the virtual trade of externalities

Understanding how countries contribute to the generation of externalities globally is important for designing sustainable policies aimed at reducing negative externalities such as carbon emissions. Commonly used approaches focus on either producers or consumers, thereby neglecting the role of intermediates. We here introduce the concept of throughflow to comprehensively quantify upstream externalities generated by the supply chains originating from, passing through or ending in a given country. We define the Throughflow Based Accounting (TBA) framework as the decomposition of the throughflow into local, imported, exported and traversing externalities. We illustrate the strength of the TBA by identifying the CO2 emissions caused by supply chains involving the German economy. We show that Germany could use its position in global value chains to help reduce two times more CO2 emissions than measured with usual production- or consumption-based accounting frameworks.Industrial Ecolog

Nonlinear oscillator with parametric colored noise: some analytical results

The asymptotic behavior of a nonlinear oscillator subject to a multiplicative Ornstein-Uhlenbeck noise is investigated. When the dynamics is expressed in terms of energy-angle coordinates, it is observed that the angle is a fast variable as compared to the energy. Thus, an effective stochastic dynamics for the energy can be derived if the angular variable is averaged out. However, the standard elimination procedure, performed earlier for a Gaussian white noise, fails when the noise is colored because of correlations between the noise and the fast angular variable. We develop here a specific averaging scheme that retains these correlations. This allows us to calculate the probability distribution function (P.D.F.) of the system and to derive the behavior of physical observables in the long time limit

Outbreak of West Nile virus causing severe neurological involvement in children, Nuba Mountains, Sudan, 2002.

An atypical outbreak of West Nile virus (WNV) occurred in Ngorban County, South Kordophan, Sudan, from May to August 2002. We investigated the epidemic and conducted a case-control study in the village of Limon. Blood samples were obtained for cases and controls. Patients with obvious sequelae underwent cerebrospinal fluid (CSF) sampling as well. We used enzyme-linked immunosorbent assay (ELISA) and neutralization tests for laboratory diagnosis and identified 31 cases with encephalitis, four of whom died. Median age was 36 months. Bivariate analysis did not reveal any significant association with the risk factors investigated. Laboratory analysis confirmed presence of IgM antibodies caused by WNV in eight of 13 cases, indicative of recent viral infection. The unique aspects of the WNW outbreak in Sudan, i.e. disease occurrence solely among children and the clinical domination of encephalitis, involving severe neurological sequelae, demonstrate the continuing evolution of WNV virulence. The spread of such a virus to other countries or continents cannot be excluded

Segmentation of the Himalayas as revealed by arc-parallel gravity anomalies

International audienceLateral variations along the Himalayan arc are suggested by an increasing number of studies and carry important information about the orogen’s segmentation. Here we compile the hitherto most complete land gravity dataset in the region which enables the currently highest resolution plausible analysis. To study lateral variations in collisional structure we compute arc-parallel gravity anomalies (APaGA) by subtracting the average arc-perpendicular profile from our dataset; we compute likewise for topography (APaTA). We find no direct correlation between APaGA, APaTA and background seismicity, as suggested in oceanic subduction context. In the Himalayas APaTA mainly reflect relief and erosional effects, whereas APaGA reflect the deep structure of the orogen with clear lateral boundaries. Four segments are outlined and have disparate flexural geometry: NE India, Bhutan, Nepal & India until Dehradun, and NW India. The segment boundaries in the India plate are related to inherited structures, and the boundaries of the Shillong block are highlighted by seismic activity. We find that large earthquakes of the past millennium do not propagate across the segment boundaries defined by APaGA, therefore these seem to set limits for potential rupture of megathrust earthquakes

Suppression of growth by multiplicative white noise in a parametric resonant system

The author studied the growth of the amplitude in a Mathieu-like equation with multiplicative white noise. The approximate value of the exponent at the extremum on parametric resonance regions was obtained theoretically by introducing the width of time interval, and the exponents were calculated numerically by solving the stochastic differential equations by a symplectic numerical method. The Mathieu-like equation contains a parameter $\alpha$ that is determined by the intensity of noise and the strength of the coupling between the variable and the noise. The value of $\alpha$ was restricted not to be negative without loss of generality. It was shown that the exponent decreases with $\alpha$, reaches a minimum and increases after that. It was also found that the exponent as a function of $\alpha$ has only one minimum at $\alpha \neq 0$ on parametric resonance regions of $\alpha = 0$. This minimum value is obtained theoretically and numerically. The existence of the minimum at $\alpha \neq 0$ indicates the suppression of the growth by multiplicative white noise.Comment: The title and the description in the manuscript are change