PDGF regulates the actin cytoskeleton through hnRNP-K-mediated activation of the ubiquitin E-3-ligase MIR

PDGF is a potent chemotactic mitogen and a strong inductor of fibroblast motility. In Swiss 3T3 fibroblasts, exposure to PDGF but not EGF or IGF-1 causes a rapid loss of actin stress fibers (SFs) and focal adhesions (FAs), which is followed by the development of retractile dendritic protrusions and induction of motility. The PDGF-specific actin reorganization was blocked by inhibition of Src-kinase and the 26S proteasome. PDGF induced Src-dependent association between the multifunctional transcription/translation regulator hnRNP-K and the mRNA-encoding myosin regulatory light-chain (MRLC)-interacting protein (MIR), a E3-ubiquitin ligase that is MRLC specific. This in turn rapidly increased MIR expression, and led to ubiquitination and proteasome-mediated degradation of MRLC. Downregulation of MIR by RNA muting prevented the reorganization of actin structures and severely reduced the migratory and wound-healing potential of PDGF-treated cells. The results show that activation of MIR and the resulting removal of diphosphorylated MRLC are essential for PDGF to instigate and maintain control over the actin-myosin-based contractile system in Swiss 3T3 fibroblasts. The PDGF induced protein destabilization through the regulation of hnRNP-K controlled ubiquitin-ligase translation identifies a novel pathway by which external stimuli can regulate phenotypic development through rapid, organelle-specific changes in the activity and stability of cytoskeletal regulators.

In vitro evaluation of the microbiota modulation abilities of different sized whole oat grain flakes.

Epidemiological studies and healthy eating guidelines suggest a positive correlation between ingestion of whole grain cereal and food rich in fibre with protection from chronic diseases. The prebiotic potential of whole grains may be related, however, little is known about the microbiota modulatory capability of oat grain or the impact processing has on this ability. In this study the fermentation profile of whole grain oat flakes, processed to produce two different sized flakes (small and large), by human faecal microbiota was investigated in vitro. Simulated digestion and subsequent fermentation by gut bacteria was investigated using pH controlled faecal batch cultures inoculated with human faecal slurry. The different sized oat flakes, Oat 23’s (0.53–0.63 mm) and Oat 25’s/26’s (0.85–1.0 mm) were compared to oligofructose, a confirmed prebiotic, and cellulose, a poorly fermented carbohydrate. Bacterial enumeration was carried out using the culture independent technique, fluorescent in situ hybridisation, and short chain fatty acid (SCFA) production monitored by gas chromatography. Significant changes in total bacterial populations were observed after 24 h incubation for all substrates except Oat 23’s and cellulose. Oats 23’s fermentation resulted in a significant increase in the Bacteroides–Prevotella group. Oligofructose and Oats 25’s/26’s produced significant increases in Bifidobacterium in the latter stages of fermentation while numbers declined for Oats 23’s between 5 h and 24 h. This is possibly due to the smaller surface area of the larger flakes inhibiting the simulated digestion, which may have resulted in increased levels of resistant starch (Bifidobacterium are known to ferment this dietary fibre). Fermentation of Oat 25’s/26’s resulted in a propionate rich SCFA profile and a significant increase in butyrate, which have both been linked to benefiting host health. The smaller sized oats did not produce a significant increase in butyrate concentration. This study shows for the first time the impact of oat grain on the microbial ecology of the human gut and its potential to beneficially modulate the gut microbiota through increasing Bifidobacterium population.

Penser la strategie de l'Antiquité à nos jours

Déjà utilisé dans un sens large à Byzance au VIe, le terme « stratégie » ne tut adopté en Europe occidentale qu’au XVIIIe siècle. Dans cet ouvrage, l’auteur définit la stratégie est une voie globale pour parvenir à des fins politiques, utilisant la menace ou l’usage effectif de la force et prenant en compte les moyens disponibles, mais aussi les valeurs et les objectifs des adversaires, dans une dialectique des volontés des adversaires. Ces variables sont au centre de cet ouvrage. Depuis Aristote et la notion de guerre juste développée par Augustin d’Hippone et Thomas d’Aquin, jusqu’au « paradigme napoléonien », qui a dominé la stratégie et la guerre à partir de la fin de l’époque moderne, et le concept de la guerre totale de Ludendorff, Béatrice Heuser expose l’évolution d’un discours sur la guerre et sa justification (ou non) comme recherche de la paix. Si, après Napoléon et Clausewitz, la victoire militaire apparaît comme le but ultime de tout conflit, à partir de la Première Guerre mondiale, et surtout de l’utilisation de la bombe atomique en 1945, les stratégistes redécouvrent l’importance de penser la paix après la guerre, le « paradigme de la paix ». Les développements de la stratégie navale, puis des stratégies aériennes et nucléaires, ainsi que les concepts de petite guerre ou de guérilla, qui dominent l’actualité, prennent leur place dans cette histoire de la stratégie, ou « comment les hommes ont pensé la guerre .

Social entrepreneurship in South Africa: exploring the influence of environment

The influence of environment on social entrepreneurship requires more concerted examination. This paper contributes to emerging discussions in this area through consideration of social entrepreneurship in South Africa. Drawing upon qualitative case study research with six social enterprises, and examined through a framework of new institutional theories and writing on new venture creation, this research explores the significance of environment for the process of social entrepreneurship, for social enterprises, and for social entrepreneurs. Our findings provide insights on institutional environments, social entrepreneurship, and the interplay between them in the South African context, with implications for wider social entrepreneurship scholarship.