Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles

Membrane vesicles (MVs) released from bacteria participate in cell communication and host-pathogen interactions. Roles for MVs in antibiotic resistance are gaining increased attention and in this study we investigated if known anti-bacterial effects of cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, could be in part attributed to effects on bacterial MV profile and MV release. We found that CBD is a strong inhibitor of MV release from Gram-negative bacteria (E. coli VCS257), while inhibitory effect on MV release from Gram-positive bacteria (S. aureus subsp. aureus Rosenbach) was negligible. When used in combination with selected antibiotics, CBD significantly increased the bactericidal action of several antibiotics in the Gram-negative bacteria. In addition, CBD increased antibiotic effects of kanamycin in the Gram-positive bacteria, without affecting MV release. CBD furthermore changed protein profiles of MVs released from E. coli after 1 h CBD treatment. Our findings indicate that CBD may pose as a putative adjuvant agent for tailored co-application with selected antibiotics, depending on bacterial species, to increase antibiotic activity, including via MV inhibition, and help reduce antibiotic resistance

A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release

Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced ‘medium-sized’ EVs (CVB1i-mEVs). These mEVs (100–300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection

Energy and Climate Implications for Agricultural Nutrient Use Efficiency

Energy and climate change are beginning to dominate the global political agenda and will drive policy formation that will shape the future of agriculture. Energy issues threaten national security and economic stability, as well as access to low-cost nutrient inputs for agriculture. Climate change has the potential to cause serious disruption to agricultural productivity. Paradoxically, nutrient use in agriculture to increase crop yields has the potential to negatively impact climate. This chapter will discuss recent and future energy and climate trends, the relationships between agricultural nutrient use efficiency and biofuels, and how global land limitations will shape agriculture in the future. Comparative gross energy yield and nitrogen use efficiency for ethanol production from crop residue, switchgrass, grain sorghum, sweet sorghum, and corn grain is presented, showing small differences in nitrogen use efficiency, but large differences in gross energy yields. In addition to considering the need to increase crop productivity to meet the demands of a growing population and bioenergy, agricultural nutrient use efficiency must be reconsidered with respect to the important energy and climate challenges shaping agriculture today

Modest improvements of survival for patients with small cell lung cancer aged 45 to 59 years only, diagnosed in the Netherlands, 1989 to 2008.

Item does not contain fulltextINTRODUCTION: Lung cancer was a major epidemic in the last decades; 10 to 15% of lung cancer consists of small cell lung cancer (SCLC). Several changes in the diagnostic and treatment procedures took place during the last 20 years. This article focuses on trends in incidence, treatment, and survival of SCLC observed since the 1990 s. METHODS: All cases with SCLC diagnosed in 1989 to 2009 in the Netherlands were included (n = 34,100). Follow-up was complete until January 1, 2010. RESULTS: The proportion of patients with extensive disease increased from 47 to 63%. The proportion of patients with limited disease receiving chemoradiation increased from 22% in 1989 to 2003 to 72% in 2004 to 2009 among those younger than 45 to 59 years, from 15 to 58% among those aged 60 to 74 years, and from 7 to 27% among those 75 years or older. Among patients with extensive disease, the proportion receiving chemotherapy remained stable over time (84, 75, and almost 50% for the above mentioned age groups, respectively). Significant improvements in 1-year relative survival occurred for patients aged 45 to 59 years, but not for the other age groups. Relative survival has significantly increased for both stage groups. CONCLUSION: Improved staging resulted in improved survival for both stage groups, whereas survival of the total group has only significantly improved for patients aged 45 to 59 years. The latter is possibly related with improved treatment strategies. As survival is still very poor, prevention of lung cancer remains important.1 januari 201