The emerging role of retromer in neuroprotection

Efficient sorting and transportation of integral membrane proteins, such as ion channels, nutrient transporters, signalling receptors, cell-cell and cell-matrix adhesion molecules is essential for the function of cellular organelles and hence organism development and physiology. Retromer is a master controller of integral membrane protein sorting and transport through one of the major sorting station within eukaryotic cells, the endosomal network. Subtle de-regulation of retromer is an emerging theme in the pathoetiology of Parkinson's disease. Here we summarise recent advances in defining the neuroprotective role of retromer and how its de-regulation may contribute to Parkinson's disease by interfering with: lysosomal health and protein degradation, association with accessory proteins including the WASH complex and mitochondrial health

Investigation of a scalable barrel atmospheric plasma reactor for the treatment of polymer particles

This study reports on the performance of a scalable barrel atmospheric plasma system for the treatment of polymer particles. A novel feature of the barrel system design is the use of a biased electrode, which also acts as the roller for the glass barrel. The plasma is generated using either helium or helium / oxygen gas mixtures. The reactor was used to activate 20 g batches of silicone, polypropylene (PP), acrylonitrile butadiene styrene (ABS) and polyethylene terephthalate (PET) particles, each with diameters in the range 3 to 5 mm. The effect of plasma treatment time and gas flow rate on the water contact angle of the treated polymer particles was examined. The polymer water contact angles decreased from up to 140° to less than 10° after the barrel plasma treatment (polymer dependent). X-ray photoelectron spectroscopy (XPS) analysis is used to monitor the effect of the plasma treatment on both PET and silicone polymer particles. Optical emission spectroscopy (OES) was used as a diagnostic tool to monitor changes in atomic and molecular species intensity with experimental conditions. Emission lines of helium, oxygen and molecular bands of OH, N2 and N2+ were monitored and correlated with their spatial distribution within the plasma chamber. Electrical characterisation studies demonstrated an increase in plasma power with increasing input voltage and helium flow rate. The heating effect of the plasma was monitored using an infrared thermographic camera, the maximum barrel temperature after 30 minutes treatment found to be 29°C. While the current barrel plasma system design can treat 20 g of polymer the system design has the potential to be readily scalable for the activation of larger batches of particles

Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?

BACKGROUND: Lymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4-6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped. METHODOLOGY/PRINCIPAL FINDINGS: In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded. CONCLUSIONS: Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013

Voltage gated inter-cation selective ion channels from graphene nanopores

With the ability to selectively control ionic flux, biological protein ion channels perform a fundamental role in many physiological processes. For practical applications that require the functionality of a biological ion channel, graphene provides a promising solid-state alternative, due to its atomic thinness and mechanical strength. Here, we demonstrate that nanopores introduced into graphene membranes, as large as 50 nm in diameter, exhibit inter-cation selectivity with a ~20x preference for K+ over divalent cations and can be modulated by an applied gate voltage. Liquid atomic force microscopy of the graphene devices reveals surface nanobubbles near the pore to be responsible for the observed selective behavior. Molecular dynamics simulations indicate that translocation of ions across the pore likely occurs via a thin water layer at the edge of the pore and the nanobubble. Our results demonstrate a significant improvement in the inter-cation selectivity displayed by a solid-state nanopore device and by utilizing the pores in a de-wetted state, offers an approach to fabricating selective graphene membranes that does not rely on the fabrication of sub-nm pores

IP3 3-kinase opposes NGF driven neurite outgrowth.

The inositol (1,4,5) trisphosphate 3-kinases comprise a family of enzymes (A, B, and C) that phosphorylate the calcium mobilising molecule inositol (1,4,5) trisphosphate (IP(3)) to generate inositol (1,3,4,5) tetrakisphosphate. This molecule can function as a second messenger, but its roles are not completely understood. The A isoform of inositol (1,4,5) trisphosphate 3-kinase localises to filamentous actin within dendritic spines in the hippocampus and is implicated in the regulation of spine morphology and long term potentiation, however the mechanisms through which it signals in neuronal cells are not completely understood. We have used NGF driven neurite outgrowth from PC12 cells as a platform to examine the impact of signaling via inositol (1,4,5) trisphosphate 3-kinase activity in a neuronal cell. We have found that the catalytic activity of the enzyme opposes neurite outgrowth, whilst pharmacological inhibition of inositol (1,4,5) trisphosphate 3-kinase leads to a significant increase in neurite outgrowth, and we show that the reduction in neurite outgrowth in response to inositol (1,4,5) trisphosphate 3-kinase activity correlates with reduced ERK activity as determined by western blotting using phosphorylation-specific antibodies. Our findings suggest a novel neuronal signaling pathway linking metabolism of IP(3) to signaling via ERK