PPAR Gamma Activity and Control of Bone Mass in Skeletal Unloading

Bone loss occuring with unloading is associated with decreased osteoblastogenesis and increased bone marrow adipogenesis, resulting in bone loss and decreased bone formation. Here, we review the present knowledge on the role of PPARγ in the control of osteoblastogenesis and bone mass in skeletal unloading. We showed that PPARγ positively promotes adipogenesis and negatively regulates osteoblast differentiation of bone marrow stromal cells in unloading, resulting in bone loss. Manipulation of PPARγ2 expression by exogenous TGF-β2 inhibits the exaggerated adipogenesis and corrects the balance between osteoblastogenesis and adipogenesis induced by unloading, leading to prevention of bone loss. This shows that PPARγ plays an important role in the control of bone mass in unloaded bone. Moreover, this opens the possibility that manipulation of PPARγ may correct the balance between osteoblastogenesis and adipogenesis and prevent bone loss, which may have potential implications in the treatment of bone loss in clinical conditions

Retour sur la première expérience de l’hybridation par le solaire PV des centrales de production d’électricité conventionnelles alimentant les Réseaux Insulaires du Grand Sud Algérien

The Algerian electric system consists of the northern interconnected grid, the “Pôle In Salah – Adrar – Timimoun” regional grid and many mini-grids supplying dispersed localities in the Great Algerian South. Although these mini-grids share, as of end-2018, only 4% of the whole country power generation capacity, the huge renewable energies, mainly solar PV, potential availability stimulates, in the framework of the efforts deployed towards a low-carbon energy transition, to integrate PV to existing fossil fuels-based power plants. In this context, this paper presents the first attempt achieved by SKTM, a subsidiary of Sonelgaz, by the integration of PV power plants to the power generation systems supplying Tamanrasset, Tindouf and Djanet localities. Positive outcomes in terms of fuel saving and CO2 emissions reduction which would be retrieved from this first experience are highlighted

Abrogation of Cbl–PI3K Interaction Increases Bone Formation and Osteoblast Proliferation

Cbl is an adaptor protein and E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and phosphorylated by Src family kinases. Phosphorylated CblY737 creates a binding site for the p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) that also plays an important role in the regulation of bone homeostasis. To investigate the role of Cbl–PI3K interaction in bone homeostasis, we examined knock-in mice in which the PI3K binding site on Cbl was ablated due to the substitution of tyrosine 737 to phenylalanine (CblYF/YF, YF mice). We previously reported that bone volume in these mice is increased due to decreased osteoclast function (Adapala et al., J Biol Chem 285:36745–36758, 19). Here, we report that YF mice also have increased bone formation and osteoblast numbers. In ex vivo cultures bone marrow-derived YF osteoblasts showed increased Col1A expression and their proliferation was also significantly augmented. Moreover, proliferation of MC3T3-E1 cells was increased after treatment with conditioned medium generated by culturing YF bone marrow stromal cells. Expression of stromal derived factor-1 (SDF-1) was increased in YF bone marrow stromal cells compared to wild type. Increased immunostaining of SDF-1 and CXCR4 was observed in YF bone marrow stromal cells compared to wild type. Treatment of YF condition medium with neutralizing anti-SDF-1 and anti-CXCR4 antibodies attenuated MC3T3-E1 cell proliferation. Cumulatively, these results show that abrogation of Cbl–PI3K interaction perturbs bone homeostasis, affecting both osteoclast function and osteoblast proliferation

A formal classification of the Lygeum spartum vegetation of the Mediterranean Region

Aims We examined local and regional contribution on the grasslands dominated by Lygeum spartum from Southern Europe and North Africa to produce a formalised classification of this vegetation and to identify main factors driving its plant species composition. Location Mediterranean Basin and Iberian Peninsula. Methods We used a dataset of 728 relevés, which were resampled to reduce unbalanced sampling effort, resulting in a dataset of 568 relevés and 846 taxa. We classified the plots by TWINSPAN, interpreted the resulting pools, and used them to develop formal definitions of phytosociological alliances characterised by L. spartum vegetation. The definitions were included in an expert system to assist automatic vegetation classification. We related the alliances to climatic factors and described their biogeographical features and ecological preferences. The floristic relationships between these alliances were analysed and visualised using distance‐based redundancy analysis. Results We defined eleven alliances of L. spartum vegetation, including the newly described Launaeo laniferae‐Lygeion sparti from SW Morocco and the Noaeo mucronatae‐Lygeion sparti from the Algerian highlands and NE Morocco. Biogeographical, climatic, and edaphic factors were revealed as putatively driving the differentiation between the alliances. The vegetation of clayey slopes and inland salt basins displayed higher variability in comparison with those of coastal salt marshes. Main conclusions The most comprehensive formal classification, accompanied by an expert system, of the L. spartum vegetation was formulated. The expert system, containing the formal definitions of the phytosociological alliances, will assist in identification of syntaxonomic position of new datasets

The Ubiquitin/Proteasome System Mediates Entry and Endosomal Trafficking of Kaposi's Sarcoma-Associated Herpesvirus in Endothelial Cells

Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin β1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin β1, and identify c-Cbl as a potential E3 ligase that facilitates this process

Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit Levels

BACKGROUND: During myogenesis several transcription factors and regulators of protein synthesis and assembly are rapidly degraded by the ubiquitin-proteasome system (UPS). Given the potential role of the deubiquitinating enzyme (DUB) ataxin-3 in the UPS, and the high expression of the murine ataxin-3 homolog in muscle during embryogenesis, we sought to define its role in muscle differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence analysis, we found murine ataxin-3 (mATX3) to be highly expressed in the differentiated myotome of E9.5 mouse embryos. C2C12 myoblasts depleted of mATX3 by RNA interference exhibited a round morphology, cell misalignment, and a delay in differentiation following myogenesis induction. Interestingly, these cells showed a down-regulation of alpha5 and alpha7 integrin subunit levels both by immunoblotting and immunofluorescence. Mouse ATX3 was found to interact with alpha5 integrin subunit and to stabilize this protein by repressing its degradation through the UPS. Proteomic analysis of mATX3-depleted C2C12 cells revealed alteration of the levels of several proteins related to integrin signaling. CONCLUSIONS: Ataxin-3 is important for myogenesis through regulation of integrin subunit levels.This work was financed by the Fundacao para a Ciencia e a Tecnologia (FCT) (POCI/SAU-MMO/60412/2002) and by National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) grant RO1 NS038712 to HLP. MCC, FB, AJR, and RJT were supported by the FCT fellowships (SFRH/BD/9759/2003 and SFRH/BPD/28560/2006), (SFRH/BPD/17368/2004), (SFRH/BD/17066/2004), (SFRH/BD/29947/2006), respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Integrated supply–demand energy management for optimal design of off-grid hybrid renewable energy systems for residential electrification in arid climates

The growing research interest in hybrid renewable energy systems (HRESs) has been regarded as a natural and yet critical response to address the challenge of rural electrification. Based on a Bibliometric analysis performed by authors, it was concluded that most studies simply adopted supply-side management techniques to perform the design optimization of such a renewable energy system. To further advance those studies, this paper presents a novel approach by integrating demand-supply management (DSM) with particle swarm optimization and applying it to optimally design an off-grid hybrid PV-solar-diesel-battery system for the electrification of residential buildings in arid environments, using a typical dwelling in Adrar, Algeria, as a case study. The proposed HRES is first modelled by an in-house MATLAB code based on a multi-agent system concept and then optimized by minimizing the total net present cost (TNPC), subject to reliability level and renewable energy penetration. After validation against the HOMER software, further techno-economic analyses including sensitivity study are undertaken, considering different battery technologies. By integrating the proposed DSM, the results have shown the following improvements: with RF = 100%, the energy demand and TNPC are reduced by 7% and 18%, respectively, compared to the case of using solely supply-side management. It is found that PV-Li-ion represents the best configuration, with TNPC of $23,427 and cost of energy (COE) of 0.23$/kWh. However, with lower RF values, the following reductions are achieved: energy consumption (19%) and fuel consumption or CO 2 emission (57%), respectively. In contrast, the RF is raised from 15% (without DSM) to 63% (with DSM). It is clear that the optimal configuration consists of wind-diesel, with COE of 0.21 $/kWh, smaller than that obtained with a stand-alone diesel generator system. The outcomes of this work can provide valuable insights into the successful design and deployment of HRES in Algeria and surrounding regions

Les groupements vegetaux de la region de Bou Saada (Algerie); essai de synthese sur la vegetation steppique du Maghreb

SIGLEINIST T 73176 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Contribution à l'optimisation du dimensionnement de générateur photovoltaïque et de banc de batteries dans un système hybride de production d'électricité (éolien - photovoltaïque) totalement autonome

95 p. : ill. ; 30 c