Host defense against Pseudomonas aeruginosa requires ceramide- rich membrane rafts

Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen

Apple production and apple value chains in Europe

This paper presents an overview of the apple sector in nine major apple producing countries in Europe, in order to assess factors for the competitiveness of the national apple value chains and identify challenges for the future development of the sector. Based on international and national statistical data and expert assessment, key characteristics of apple production and value chains are analyzed. For each country, a brief description of the development of apple production and acreage over the past ten years, farm size distribution, level of production technology and main market channels is presented, followed by a discussion of differences and similarities. Results show a diverse picture of the apple sectors in Europe. Similarities are observed in the existence of regional production clusters and a generally small farm size. Differences are found in the technology level, with a broad range of very traditional extensive production systems up to highly intensified orchards with high tree density. All countries experienced high fluctuation in apple production quantities over the past years, mainly due to weather events, particularly spring frost and drought, and climate risks are expected to increase in the future, leading to increasing costs for mitigation measure

HSP72 protects against obesity-induced insulin resistance

Patients with type 2 diabetes have reduced gene expression of heat shock protein (HSP) 72, which correlates with reduced insulin sensitivity. Heat therapy, which activates HSP72, improves clinical parameters in these patients. Activation of several inflammatory signaling proteins such as c-jun amino terminal kinase (JNK), inhibitor of κB kinase, and tumor necrosis factor-α, can induce insulin resistance, but HSP 72 can block the induction of these molecules in vitro. Accordingly, we examined whether activation of HSP72 can protect against the development of insulin resistance. First, we show that obese, insulin resistant humans have reduced HSP72 protein expression and increased JNK phosphorylation in skeletal muscle. We next used heat shock therapy, transgenic overexpression, and pharmacologic means to overexpress HSP72 either specifically in skeletal muscle or globally in mice. Herein, we show that regardless of the means used to achieve an elevation in HSP72 protein, protection against diet- or obesity-induced hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance was observed. This protection was tightly associated with the prevention of JNK phosphorylation. These findings identify an essential role for HSP72 in blocking inflammation and preventing insulin resistance in the context of genetic obesity or high-fat feeding