Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma

Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated. Upregulation of WNT/beta-catenin signaling induces changes in key metabolic enzyme that modify their thermodynamics behavior. This leads to activation pyruvate dehydrogenase kinase 1(PDK-1) and monocarboxylate lactate transporter 1 (MCT-1). Consequently, phosphorylation of PDK-1 inhibits pyruvate dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot be converted into acetyl-CoA in mitochondria and in TCA (tricarboxylic acid) cycle. This leads to aerobic glycolysis despite the availability of oxygen, named Warburg effect. Cytoplasmic pyruvate is, in major part, converted into lactate. The WNT/beta-catenin pathway induces also the transcription of genes involved in cell proliferation, cell invasiveness, nucleotide synthesis, tumor growth, and angiogenesis, such as c-Myc, cyclin D1, PDK. In addition, in gliomas cells, PPAR gamma is downregulated, leading to a decrease in insulin sensitivity and an increase in neuroinflammation. Moreover, PPAR gamma contributes to regulate some key circadian genes. Abnormalities in the regulation of circadian rhythms and dysregulation in circadian clock genes are observed in gliomas. Circadian rhythms are dissipative structures, which play a key role in far-from-equilibrium thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR gamma. In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly interrelated

Output error methods for robot identification

Industrial robot identification is usually based on the inverse dynamic model (IDIM) that comes from Newton’s laws and has the advantage of being linear with respect to the parameters. Building the IDIM from the measurement signals allows the use of linear regression techniques like the least-squares (LS) or the instrumental variable (IV) for instance. Nonetheless, this involves a careful preprocessing to deal with sensor noise. An alternative in system identification is to consider an output error approach where the model’s parameters are iteratively tuned in order to match the simulated model’s output and the measured system’s output. This paper proposes an extensive comparison of three different output error approaches in the context of robot identification. One of the main outcomes of this work is to show that choosing the input torque as target identification signal instead of the output position may lead to a gain in robustness versus modeling errors and noise and in computational time. Theoretical developments are illustrated on a six degrees-of-freedom rigid robo

Lower function, quality of life, and survival rate after total knee arthroplasty for posttraumatic arthritis than for primary arthritis

International audienceBackground and purpose - Total knee arthroplasty (TKA) for treatment of end-stage posttraumatic arthritis (PTA) has specific technical difficulties and complications. We compared clinical outcome, postoperative quality of life (QOL), and survivorship after TKA done for PTA with those after TKA performed for primary arthritis (PA). Patients and methods - We retrospectively reviewed patients who were operated on at our institution for PTA between 1998 and 2005 (33 knees), and compared them to a matched group of patients who were operated on for PA during the same period (407 knees). Clinical outcomes and postoperative QOL were compared in the 2 groups using Knee Society score (KSS), range of motion (ROM) of the knee, and the knee osteoarthritis outcomes score (KOOS). Implant survival rate was calculated using Kaplan-Meier analysis. Results - At a mean follow-up of 11 (5-15) years, KSS knee increased from mean 39 (SD 18) to 87 (SD 16) in the PA group (p = 0.003), and from 31 (SD 11) to 77 (SD 15) in the PTA group (p = 0.003). KSS function increased from 55 (12) to 89 (25) in the PA group (p = 0.008) and from 44 (SD 14) to 81 (SD 10) in the PTA group (p = 0.008). Postoperative ROM also improved in both groups, from 83 degrees to 108 degrees in the PTA group (p < 0.001) as opposed to 116 degrees to 127 degrees in the PA group (p = 0.001), with lower results in the PTA group (p < 0.001). KOOS was lower in the PTA group (p < 0.001). The survival rate of TKA at 10 years with an endpoint defined as "any surgery on the operated knee" showed better results in the PA group (99%, CI: 98-100 vs. 79%, CI: 69-89; p < 0.001). Interpretation - Patients and surgeons should be aware that clinical outcome and implant survival after TKA for PTA are lower than after TKA done for P

Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein

We have previously reported that the CDX1 homeoprotein interacts with the TATA-box binding protein (TBP) on the promoter of the glucose-6-phosphatase (G6Pase) gene. We show here that CDX1 interacts with TBP via the homeodomain and that the transcriptional activity additionally requires the N-terminal domain upstream of the homeodomain. CDX1 interacting with TBP is connected to members of the TFIID and Mediator complexes, two major elements of the general transcriptional machinery. Transcription luciferase assays performed using an altered-specificity mutant of TBP provide evidence for the functionality of the interaction between CDX1 and TBP. Unlike CDX1, CDX2 does not interact with TBP nor does it transactivate the G6Pase promoter. Swapping experiments between the domains of CDX1 and CDX2 indicate that, despite opposite functional effects of the homeoproteins on the G6Pase promoter, the N-terminal domains and homeodomains of both CDX1 and CDX2 have the intrinsic ability to activate transcription and to interact with TBP. However, the carboxy domains define the specificity of CDX1 and CDX2. Thus, intra-molecular interactions control the activity and partner recruitment of CDX1 and CDX2, leading to different molecular functions

Mesenchymal Stem Cells in Systemic Sclerosis: Allogenic or Autologous Approaches for Therapeutic Use?

Systemic sclerosis (SSc) is a rare autoimmune disease, which is potentially lethal. The physiopathology of the disease is still incompletely elucidated although the role of fibroblasts, endothelial cells (ECs), immune cells. and the environment (i.e., oxidative stress) has been demonstrated. This is an intractable disease with an urgent need to provide better therapeutic options to patients. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach thanks to the number of trophic and pleiotropic properties they exert. Among these, MSCs display anti-fibrotic, angiogenic, and immunomodulatory capacities that might be of interest in the treatment of SSc by acting on different processes that are dysregulated in the disease. In the recent years, the therapeutic effectiveness of MSCs has been demonstrated in different preclinical animal models and is being investigated in phase I clinical trials. Both allogenic and autologous transplantation of MSCs isolated from bone marrow or adipose tissue is being evaluated. The rationale for using allogenic MSCs in SSc, as well as in other autoimmune diseases, is based on the possibility that autologous MSCs might be altered in these diseases. In SSc, reports from the literature are controversial. Nevertheless, the role of the oxidative environment and of the crosstalk with neighboring cells (fibroblasts and ECs) on the functional properties of MSCs has been reported. Here, we review the preclinical and clinical data reporting the interest of MSC-based treatment in SSc and question the use of autologous or allogeneic MSCs in perspective of clinical applications

Preliminary Experiments on Unsupervised Word Discovery in Mboshi

International audienceThe necessity to document thousands of endangered languages encourages the collaboration between linguists and computer scientists in order to provide the documentary linguistics community with the support of automatic processing tools. The French-German ANR-DFG project Breaking the Unwritten Language Barrier (BULB) aims at developing such tools for three mostly unwritten African languages of the Bantu family. For one of them, Mboshi, a language originating from the " Cu-vette " region of the Republic of Congo, we investigate unsuper-vised word discovery techniques from an unsegmented stream of phonemes. We compare different models and algorithms, both monolingual and bilingual, on a new corpus in Mboshi and French, and discuss various ways to represent the data with suitable granularity. An additional French-English corpus allows us to contrast the results obtained on Mboshi and to experiment with more data

Une plateforme pour l'analyse de matériaux par faisceaux d'ions à ARRONAX : Etude de l'effet d'humidité sur les échantillons

International audienceQuantification of soil pollution with method based on X-ray detection like X-Ray Fluorescence(XRF) suffers of multiple bias (moisture, surface state) especially when it's used for insituanalysis using portable-XRF. In order to study the effect of moisture on the results of ananalysis performed using X-Ray, we have performed studies using high energy PIXE/PIGE atthe ARRONAX. Samples were made of sand of different type. High energy PIXE/PIGE allowsus to avoid bias from surface state and to focus on moisture effect. It also allows to assessthe chemical composition of the sample. Results show a different behavior for each elementpresent in volcanic sand.</p