PEARL: a programmable virtual router platform

International audienceProgrammable routers supporting virtualization are a key building block for bridging the gap between new Internet protocols and their deployment in real operational networks. This article presents the design and implementation of PEARL, a programmable virtual router platform with relatively high performance. It offers high flexibility by allowing users to control the configuration of both hardware and software data paths. The platform makes use of fast lookup in hardware and software exceptions in commodity multicore CPUs to achieve highspeed packet processing. Multiple isolated packet streams and virtualization techniques ensure isolation among virtual router instances

CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation

Runx2, an essential transactivator for osteoblast differentiation, is tightly regulated at both the transcriptional and posttranslational levels. In this paper, we report that CHIP (C terminus of Hsc70-interacting protein)/STUB1 regulates Runx2 protein stability via a ubiquitination-degradation mechanism. CHIP interacts with Runx2 in vitro and in vivo. In the presence of increased Runx2 protein levels, CHIP expression decreases, whereas the expression of other E3 ligases involved in Runx2 degradation, such as Smurf1 or WWP1, remains constant or increases during osteoblast differentiation. Depletion of CHIP results in the stabilization of Runx2, enhances Runx2-mediated transcriptional activation, and promotes osteoblast differentiation in primary calvarial cells. In contrast, CHIP overexpression in preosteoblasts causes Runx2 degradation, inhibits osteoblast differentiation, and instead enhances adipogenesis. Our data suggest that negative regulation of the Runx2 protein by CHIP is critical in the commitment of precursor cells to differentiate into the osteoblast lineage

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light−12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Pollution-Aware Walking in 16 Countries:An Application of the Theory of Planned Behaviour (TPB)

Background: The current levels of air pollution in European countries reduces life expectancy by an average of 8 months. People who actively travel by walking have a higher level of exposure to air pollution than those who use motor vehicles or electric buses. Some routes have higher air pollution levels than others, but little is known about pollution-aware route choice and intentions to actively avoid walking near polluted roads. An improved understanding of how air pollution influences intentions to walk or avoid polluted routes can inform interventions to decrease exposure. The present investigation has three aims: (1) compare experiences walking near roads with high levels of air pollution across countries; (2) identify groups of countries based on perceptions of air quality; and (3) examine how pedestrians develop their intentions of avoiding pollution using the extended TPB (demographics, social norms, attitudes, perceived control, and perceived risk).Methods: A cross-sectional design was applied. Pedestrians were asked about their experiences walking near roads with high levels of air pollution. To identify groups of countries with different levels of air pollution, a cluster analysis was implemented based on the perceptions of air quality. Finally, regressions were used to predict pedestrians’ intentions to avoid polluted roads per country group using the extended TPB.Results: 6180 respondents (Age M(SD)= 29.4(14.2); Males= 39.2%) ranging from 12.6% from Russia to 2.2% from Finland completed the questionnaire. The proportion of participants who reported never walking near air polluted roads was 12.4% (from 3% in Brazil to 54% in Japan). Seven groups of countries were identified using perceptions of air quality: G1(Japan, Mexico, Colombia, Turkey, Malaysia & Brazil), G2(Spain, Romania & Czechia), G3(Chile, Russia & Peru), G4(China), G5(Australia), G6(Finland), and G7(Portugal). Participants in China (G4) and Australia (G5) reported the worst and best air quality respectively. Across all countries, intentions to avoid polluted roads were associated with perceptions of risk. TPB-psychosocial factors such as social norms and perceived behavioural control also influenced intention in most groups. Favourable TPB-beliefs and low perceived risk increase intentions to avoid polluted routes.Conclusions: The willingness of pedestrians to walk on or near roads with high levels of air pollution differs significantly among countries in this study. Countries can be grouped based on their perceived air quality. Perceived risk was the only common predictor of intention to avoid polluted routes across the different groups of countries

The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis

The prevalence of obesity and atherosclerosis has substantially increased worldwide over the past several decades. Peroxisome proliferator-activated receptors (PPARs), as fatty acids sensors, have been therapeutic targets in several human lipid metabolic diseases, such as obesity, atherosclerosis, diabetes, hyperlipidaemia, and non-alcoholic fatty liver disease. Constitutive androstane receptor (CAR) and liver X receptors (LXRs) were also reported as potential therapeutic targets for the treatment of obesity and atherosclerosis, respectively. Further clarification of the internal relationships between these three lipid metabolic nuclear receptors is necessary to enable drug discovery. In this review, we mainly summarized the cross-talk of PPARs-CAR in obesity and PPARs-LXRs in atherosclerosis

Optimal Cache Allocation for Content-Centric Networking

Abstract—Content-Centric Networking (CCN) is a promising framework for evolving the current network architecture, advocating ubiquitous in-network caching to enhance content delivery. Consequently, in CCN, each router has storage space to cache frequently requested content. In this work, we focus on the cache allocation problem: namely, how to distribute the cache capacity across routers under a constrained total storage budget for the network. We formulate this problem as a content placement problem and obtain the exact optimal solution by a two-step method. Through simulations, we use this algorithm to investigate the factors that affect the optimal cache allocation in CCN, such as the network topology and the popularity of content. We find that a highly heterogeneous topology tends to put most of the capacity over a few central nodes. On the other hand, heterogeneous content popularity has the opposite effect, by spreading capacity across far more nodes. Using our findings, we make observations on how network operators could best deploy CCN caches capacity. I