162 WNT-6 INDUCES THE CHONDROGENIC DIFFERENTIATION OF MESENCHYMAL STEM CELLS

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The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

The Potential of microRNAs for Stem Cell-based Therapy for Degenerative Skeletal Diseases

Purpose of review: degenerative skeletal disorders including osteoarthritis (OA) and osteoporosis (OP) are the result of attenuation of tissue regeneration and lead to painful conditions with limited treatment options. Preventative measures to limit the onset of OA and OP remain a significant unmet clinical need. MicroRNAs (miRNAs) are known to be involved in the differentiation of stem cells, and in combination with stem cell therapy could induce skeletal regeneration and potentially prevent OA and OP onset.Recent findings: the combination of stem cells and miRNA has been successful at regenerating the bone and cartilage in vivo. MiRNAs, including miR-146b known to be involved in chondrogenic differentiation, could provide innovative targets for stem cell-based therapy, for the repair of articular cartilage defects forestalling the onset of OA or in the generation of a stem cell-based therapy for OP.Summary: this review discusses the combination of skeletal stem cells (SSCs) and candidate miRNAs for application in a cell-based therapy approach for skeletal regenerative medicine

Thickness of Fluvial Deposits Records Climate Oscillations

Fluvial deposits offer Earth’s best‐preserved geomorphic record of past climate change over geological timescales. However, quantitatively extracting this information remains challenging in part due to the complexity of erosion, sediment transport and deposition processes and how each of them responds to climate. Furthermore, sedimentary basins have the potential to temporarily store sediments, and rivers subsequently rework those sediments. This may introduce time lags into sedimentary signals and obscure any direct correlation with climate forcing. Here, using a numerical model that combines all three processes—and a new analytical solution—we show that the thickness of fluvial deposits at the outlet of a mountain river can be linked to the amplitude and period of rainfall oscillations but is modulated by the mountain uplift rate. For typical uplift rates of a few mm/yr, climate oscillations at Milankovitch periods lead to alluvial sediment thickness of tens of meters as observed in nature. We also explain the time lag of the order of 20%–25% of the forcing period that is commonly observed between the timing of maximum rainfall and erosion. By comparing to field datasets, our predictions for the thickness and time lag of fluvial deposits are broadly consistent with observations despite the simplicity of our modeling approach. These findings provide a new theoretical framework for quantitatively extracting information on past rainfall variations from fluvial deposits.Plain Language Summary: Climate influences the evolution of terrestrial landscapes through the amount of precipitation, which provides water to erode rocks and transport sediment in rivers. At the outlets of mountain ranges, rivers can deposit part of their sediment load; the shape of the deposits is influenced by the amount of flow in the rivers. If the climate changes such that the precipitation rate increases, rivers can cut into their own previous deposits. The remaining deposits are then abandoned above the riverbed. On the contrary, if precipitation decreases, rivers tend to deposit more sediment, leading to increases in the thickness of sediments at the outlets of mountain rivers. Thus, there is a relationship between the amount of precipitations and the thickness of sediments deposited at river outlets. We study this with a computer model that allows us to relate the variations in precipitation rates to variations in thickness of fluvial terrace deposits. This work can be used to better understand how rivers respond to climatic changes, and also to reconstruct climatic variations of the past from observed river deposits.Key Points: We use a numerical model and a new analytical solution to quantify a physical link between fluvial deposits and climate oscillations. Our method provides a theoretical framework for extracting information on past climate variations from fluvial terrace deposits. Our results explain time lag of 20%–25% of forcing period commonly observed between the timing of maximum rainfall and erosion.TOTALMarie Sklodowska‐Curie granthttps://doi.org/10.5281/zenodo.383398

ERPs obtained with the auditory oddball paradigm in coma and altered states of consciousness: clinical relationships, prognostic value, and origin of components.

OBJECTIVE: To study the event related potentials (ERPs) in coma and altered states of consciousness, their relationship with the clinical status and coma outcome. METHODS: ERPs were recorded with a passive auditory oddball paradigm in 103 patients. Their probability of occurrence and the peak latencies and amplitudes were studied as a function of the Glasgow Coma Score (GCS). Their relationship with outcome was studied in a subset of 83 patients examined within the first 4 days, and expressed in terms of sensitivity, specificity, and negative or positive prognostic values. RESULTS: When present, the ERPs to rare stimuli consisted of a fronto-central negativity (N(endog), mean latency: 330 ms) and a fronto-central positivity (P(endog), mean latency: 431 ms) following the exogenous N100-P200 complex. Both their probability of occurrence and their latencies and amplitudes were related with the GCS in anoxic and traumatic comas. The N(endog) and P(endog) had high sensitivity with a negative predictive value of 70% and 100%, respectively, but a low specificity, with a positive predictive value of 44% and 41%, respectively. CONCLUSIONS: ERPs can be recorded in some comatose patients and are likely to reflect implicit orienting processes rather than preserved consciousness. Their presence implies a good prognosis but no conclusion can be drawn from their absence

Thickness of Fluvial Deposits Records Climate Oscillations

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L'apport diagnostique et pronostique des potentiels évoqués somesthésiques par stimulation tronculaire et dermatomale dans les conflits disco-radiculaires lombaires : A propos de 120 cas opérés

Lower-limb somatosensory evoked potentials (SEPs) of nerve-trunk (peroneal nerve, posterior tibial nerve) and dermatomal (L5 and S1) stimulation were recorded in 120 patients suffering from lumbosacral disk disease. Recordings were performed before surgery and on Days 4 and 50 after surgery. Electromyography was also performed before surgery. Dermatomal SEPs were shown to be sensitive (70 %) and specific in both terms of their lateralizing value and their ability to identify the L5 or S1 level. Moreover, combining SEPs and EMG significantly increased the sensitivity of the electrophysiological testing when compared with each method alone. There was no relationship between SEPs performed before surgery and surgical outcome. Inversely, we demonstrated the prognostic value of SEPs performed on Day 4. SEP normalization at Day 4 was associated with a good outcome at Day 50 in 91.8 % of examined cases, while the persistance of pathological SEPs at Day 4 was associated with poor outcome at Day 50 in 56 % of the cases

Inverse Analysis of Pearl River Source-to-Sink System, South China: Implications for SE Tibetan Uplift and Asian Monsoon Intensities

International audienceThe uplift history of the SE Tibetan Plateau has been a highly debated topic for decades, yet this problem remains of great importance to our understanding of how the crust deforms in response to continental collision, as well as how the solid Earth and climate systems interact. In particular, two contrasting models of crustal deformation have been proposed for SE Tibetan uplift, namely the "rigid-block uplift" (Tapponnier et al., 1981; 2001), and the "crustal-flow uplift" (Royden et al., 1997; Clark and Royden, 2000). This uplift has resulted in the formation of the large Pearl River catchment running from SE Tibet to the South China Sea. Asian monsoonal rain feeds this catchment, modulates sediment transport to the marginal sea, and affects the modern topography of SE Tibet. The sedimentary sequences preserved in the Pearl River Mouth Basin (PRMB) on the northern margin of the South China Sea represent an ideal natural laboratory to understand how tectonic deformation, river erosion and climate interact in this source-to-sink system. Here, we use a new efficient landscape evolution model to undertake an inverse analysis of the Pearl River source-to-sink system since the Middle Eocene (~45 Ma), in an attempt to unravel the history of river erosion (drainage evolution), climate (monsoon intensity), and tectonics (SE Tibetan uplift) that is compatible with the observed geometries of the drainage basin and the PRMB. For this, we use a Bayesian inversion scheme in which the misfit function is constructed by comparing the observed river profile, marine sediment thickness, shelf length and surface slope to those predicted by the model. Our simulations show that the crustal-flow uplift model cannot capture the geomorphic features of the SE Tibetan Plateau, and in particular the present-day profile of the Pearl River. The rigid-block uplift model can reproduce the observed geological and geomorphic features. The best-fitting values indicate that (i) the SE Tibetan Plateau started to uplift at ~15 Ma, and (ii) the monsoon intensity, simulated here by the precipitation rate, must have decreased by a factor of ~1.9 since 10 Ma. Our simulations, consistent with previous interpretations based on provenance data (Gao et al., 2018), show that the Pearl River catchment expanded towards its near-modern configuration in the Early Miocene