Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum

Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspase-and mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH 2-terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 a-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER. © 2012 Macmillan Publishers Limited All rights reserved.

Genetic variability evaluation in a Moroccan collection of barley, Hordeum vulgare L., by means of storage proteins and RAPDS

The genetic variation existing in a set of barley (Hordeum vulgare L.) landrace samples recently collected in Morocco was estimated. Two kinds of genetic markers, seed storage proteins (hordeins) and random amplified polymorphic DNA (RAPD), were used. Only six out of 31 landraces were subjected to RAPD analysis. Both kinds of markers, RAPD and storage proteins, yielded similar results, showing that the level of variation observed in Moroccan barley was high: all landraces showed variability; 808 different storage protein patterns (multilocus associations) were observed among 1897 individuals (2.32 seeds per association, on average) with an average of 43 multilocus associations per accession. In general, genetic variation within accessions was higher than between accessions. The 100 polymorphic RAPD bands generated by 21 effective primers were able to generate enough patterns to differentiate between uniform cultivars and even between individuals in variable accessions. One of the aims of this work was to compare the effectiveness of RAPD versus storage protein techniques in assessing the variability of genetic resource collections. On average hordeins were more polymorphic than RAPDs: they showed more alternatives per band on gels and a higher percentage of polymorphic bands, although RAPDs supply a higher number of bands. Although RAPD is an easy and standard technique, storage protein analysis is technically easier, cheaper and needs less sophisticated equipment. Thus, when resources are a limiting factor and considering the cost of consumables and work time, seed storage proteins must be the technique of choice for a first estimation of genetic variation in plant genetic resource collections.

Tubular cathode prepared by a dip-coating method for low temperature DMFC

A novel tubular cathode for the direct methanol fuel cell (DMFC) is proposed, based on a tubular titanium mesh. A dip-coating method has been developed for its fabrication. The tubular cathode is composed of titanium mesh, a cathode diffusion layer, a catalyst layer, and a recast Nafion® film. The titanium mesh is present at the inner circumference of the diffusion layer, while the recast Nafion® film is at the outer circumference of the catalyst layer. A DMFC single cell with a 3.5 mgPt cm tubular cathode was able to perform as well, in terms of power density, as a conventional planar DMFC. A peak power density of 9 mW cm was reached under atmospheric air at 25 °C. © 2006 WILEY-VCH Verlag GmbH & Co. KGaA.

PtRu/Ti anodes with varying Pt:Ru ratio prepared by electrodeposition for the direct methanol fuel cell

PtRu/Ti anodes with varying Pt : Ru ratio were prepared by electrodeposition of a thin PtRu catalyst layer onto Ti mesh for a direct methanol fuel cell (DMFC). The morphology and structure of the catalyst layers were analyzed by SEM, EDX and XRD. The catalyst coating layer shows an alloy character. The relative activities of the PtRu/Ti electrodes were assessed and compared in half cell and single DMFC experiments. The results show that these electrodes are very active for the methanol oxidation and that the optimum Ru surface coverage was ca. 9 at.% for DMFC operating at 20°C and 11 at.% at 60°C. The PtRu/Ti anode shows a performance comparable to that of the conventional carbon-based anode in a DMFC operating with 0.25 M or 0.5 M methanol solution and atmosphere oxygen gas at 90°C. © the Owner Societies 2006.

Ti mesh anodes prepared by electrochemical deposition for the direct methanol fuel cell

An anode structure based on Ti mesh has been developed for the direct methanol fuel cell (DMFC). This new anode was prepared by electrochemical deposition of a ~ 3 µ m PtRu catalyst layer on ~ 50 µ m Ti mesh. It has a thinner structure compared to that of a porous carbon-based conventional anode. The Ti mesh anode shows a performance comparable to, and exceeding that, of the conventional anode in a DMFC operating with 0.25 or 0.5 M methanol solution and atmosphere oxygen at 90 C. However, it shows a lower performance of the cell when higher concentrations of methanol was employed. This may be attributed to its thin and open structure, which could facilitate the transport of methanol from the flow field to the anode catalyst layer and carbon dioxide in the opposite direction. © 2006 International Association for Hydrogen Energy.

Switching between molecular switch types by module rearrangement:Ca -enabled, H-driven 'off-on-off', H-driven YES and PASS 0 as well as H, Ca-driven AND logic operations

Several logic gates and switches can be accessed from two different combinations of a single set of fluorophore, receptor and spacer components.

Catalyst distribution and carbon nanotube morphology in multilayer forests by mixed CVD processes

Carbon nanotubes can be grown as forests of aligned fibers on a substrate with a catalyst coated prior to or added during synthesis. A major process interruption can initiate the growth of second and successive layers of forest on top or at the base of the existing layers which are thereby lifted up. We report on the generation of multilayer CNT forests where the first forest is generated either by catalyst coinjection (CCI) of ferrocene with hydrocarbon (xylene) or by catalyst predeposition (CPD) of iron followed with hydrocarbon (acetylene). Subsequent layers are then produced by CCI alone to give uniform (all CCI) or mixed (CPD and CCI) structures to study the distribution of the iron catalyst and CNT morphology and to determine whether the CPD forest templates or otherwise influences the growth of subsequent CCI forests. The bottom-up base growth of second and subsequent CCI forests is reaction rate controlled. CCI multilayer forests accumulate catalyst (iron) in a variety of distinct locations. A pre-existing CPD forest modifies subsequent CCI forest initiation, morphology, and catalyst distribution but does not itself accumulate catalyst or change appearance. © 2009 American Chemical Society.

Effects of D- and L-glucose and mannitol on retinal capillary cells:Inhibition by nanomolar aminoguanidine

Hyperglycemia may contribute directly to pericyte loss and capillary leakage in early diabetic retinopathy. To elucidate relative contributions of glycation, glycoxidation, sugar autoxidation, osmotic stress and metabolic effects in glucose-mediated capillary damage, we tested the effects of D-glucose, L-glucose, mannitol and the potentially protective effects of aminoguanidine on cultured bovine retinal capillary pericytes and endothelial cells. Media (containing 5 mM D-glucose) were supplemented to increase the concentration of each sugar by 5, 10, or 20 mM. Subconfluent pericytes and endothelial cells were exposed to the supplemented media in the presence or absence of aminoguanidine (1 nM-100 µM) for three days. Cell counts, viability and protein were determined. For both cell types, all three sugars produced concentration-dependent decreases in cell counts and protein content (p

Behavioural context of multi-scale species distribution models assessed by radio-tracking

Incorporating ecological processes and animal behaviour into Species Distribution Models (SDMs) is difficult. In species with a central resting or breeding place, there can be conflict between the environmental requirements of the 'central place' and foraging habitat. We apply a multi-scale SDM to examine habitat trade-offs between the central place, roost sites, and foraging habitat in . Myotis nattereri. We validate these derived associations using habitat selection from behavioural observations of radio-tracked bats. A Generalised Linear Model (GLM) of roost occurrence using land cover variables with mixed spatial scales indicated roost occurrence was positively associated with woodland on a fine scale and pasture on a broad scale. Habitat selection of radio-tracked bats mirrored the SDM with bats selecting for woodland in the immediate vicinity of individual roosts but avoiding this habitat in foraging areas, whilst pasture was significantly positively selected for in foraging areas. Using habitat selection derived from radio-tracking enables a multi-scale SDM to be interpreted in a behavioural context. We suggest that the multi-scale SDM of . M. nattereri describes a trade-off between the central place and foraging habitat. Multi-scale methods provide a greater understanding of the ecological processes which determine where species occur and allow integration of behavioural processes into SDMs. The findings have implications when assessing the resource use of a species at a single point in time. Doing so could lead to misinterpretation of habitat requirements as these can change within a short time period depending on specific behaviour, particularly if detectability changes depending on behaviour. © 2011 Gesellschaft für ökologie.

Development of a heterogeneous catalyst for lignocellulosic biomass conversion:Glucose dehydration by metal chlorides in a silica-supported ionic liquid layer

An attempt is made to immobilize the homogeneous metal chloride/EMIMCl catalyst for glucose dehydration to 5-hydroxymethylfurfural. To this end, ionic liquid fragments were grafted to the surface of SBA-15 to generate a heterogenized mimick of the homogeneous reaction medium. Despite a decrease in the surface area, the ordered mesoporous structure of SBA-15 was largely retained. Metal chlorides dispersed in such ionic liquid film are able to convert glucose to HMF with much higher yields as is possible in the aqueous phase. The reactivity order CrCl > AlCl > CuCl > FeCl is similar to the order in the ionic liquid solvent, yet the selectivity are lower. The HMF yield of the most promising CrCl-Im-SBA-15 can be improved by using a HO:DMSO mixture as the reaction medium and a 2-butanol/MIBK extraction layer. Different attempts to decrease metal chloride leaching by using different solvents are described. © 2013 American Institute of Chemical Engineers Environ Prog.

Climate change and decadal to centennial-scale periodicities recorded in a late Holocene NE Pacific marine record: Examining the role of solar forcing

We present a decadal-scale late Holocene climate record based on diatoms, biogenic silica, and grain size from a 12-m sediment core (VEC02A04) obtained from Frederick Sound in the Seymour-Belize Inlet Complex of British Columbia, Canada. Sediments are characterized by graded, massive, and laminated intervals. Laminated intervals are most common between c. 2948–2708 cal. yr BP and c. 1992–1727 cal. yr BP. Increased preservation of laminated sediments and diatom assemblage changes at this time suggest that cli- mate became moderately drier and cooler relative to the preceding and succeeding intervals. Spectral and wavelet analyses are used to test for statistically significant periodicities in time series of proxies of primary production (total diatom abundance, biogenic silica) and hydrology (grain size) preserved in the Frederick Sound record. Periodicities of c. 42–53, 60–70, 82–89, 241–243, and 380 yrs are present. Results are com- pared to reconstructed sunspot number data of Solanki et al. (2004) using cross wavelet transform to evalu- ate the role of solar forcing on NE Pacific climate. Significant common power of periodicities between c. 42– 60, 70–89, 241–243, and of 380 yrs occur, suggesting that celestial forcing impacted late Holocene climate at Frederick Sound. Replication of the c. 241–243 yr periodicity in sunspot time series is most pronounced be- tween c. 2900 cal. yr BP and c. 2000 cal. yr BP, broadly correlative to the timing of maximum preservation of laminated sedimentary successions and diatom assemblage changes. High solar activity at the Suess/de Vries band may have been manifested as a prolonged westward shift and/or weakening of the Aleutian Low in the mid-late Holocene, which would have diverted fewer North Pacific storms and resulted in the relatively dry conditions reconstructed for the Seymour-Belize Inlet Complex.

A 1300-year multi-proxy, high-resolution record from a rich fen in northern Poland:Reconstructing hydrology, land use and climate change

Here we present the first high-resolution multi-proxy analysis of a rich fen in the central-eastern European lowlands. The fen is located in the young glacial landscape of the Sta{ogonek}zki river valley. We investigated the fen's development pathways, asking three main questions: (i) what was the pattern and timing of the peatland's vegetation succession, (ii) how did land use and climate affect the succession in the fen ecosystem, and (iii) to what degree does the reconstructed hydrology for this site correlate with those of other sites in the region in terms of past climate change? Several stages of fen history were determined, beginning with the lake-to-fen transition ca. AD 700. Brown mosses dominated the sampling site from this period to the present. No human impact was found to have occurred until ca. AD 1700, when the first forest cutting began. Around AD 1890 a more significant disturbance took place-this date marks the clear cutting of forests and dramatic landscape openness. Deforestation changed the hydrology and chemistry of the mire, which was revealed by a shift in local plant and testate amoebae communities. We also compared a potential climatic signal recorded in the peat profile before AD 1700 with other sites from the region. © 2013 John Wiley & Sons, Ltd.

Organic synthesis in the interstellar medium by low-energy carbon irradiation

We present a first principles molecular dynamics (FPMD) study of the interaction of low-energy neutral carbon projectiles with amorphous solid water clusters at 30 K. Reactions involving the carbon atom at an initial energy of 11 and 1.7 eV with 30-molecule clusters have been investigated. Simulations indicate that the formation of hydroxymethylene, an intermediate in formaldehyde production, dominates at the higher energy. The reaction proceeds by fragmenting a water molecule, binding the carbon to the OH radical, and saturating the C valence with a hydrogen atom that can arise from the originally dissociated water molecule, or through a chain of proton transfer events. We identified several possible pathways for the formation of HCOH. When the initial collision occurs at the periphery of the cluster, we observe the formation of CO and the evaporation of water molecules. At the lower energy water fragmentation is not favorable, thus leading to the formation of weakly bound carbon-water complexes. © 2013 American Chemical Society.

A high resolution 15,600-year pollen and microcharcoal record from the Cederberg Mountains, South Africa

The Cederberg Mountains (Western Cape Province, South Africa) are located within the Fynbos Biome, which exhibits some of the highest levels of species richness and endemism in the world. The region's post-glacial vegetation history, however, remains largely unknown. Presented here are high resolution pollen and microcharcoal records spanning the last 15,600 years obtained from the De Rif rock hyrax midden from the Driehoek Valley of the central Cederberg. In this region, previous pollen studies have shown muted variability in vegetation community composition during periods of globally marked climatic variability (e.g. the last glacial-interglacial transition). In our record, however, significant changes in vegetation composition are apparent. Most notably, they indicate a shift from ericaceous/restioid fynbos (present from 15,600 to 13,300 cal yr BP) to a brief, but prominent, development of proteoid fynbos at the beginning of the Holocene around 11,200 cal yr BP. This vegetation shift is associated with increased moisture at the site, and coincides with reduced fire frequency as indicated by the microcharcoal record. At 10,400 cal yr BP, there is a marked reduction in Protea-type pollen, which is replaced by thicket, characterised by Dodonaea, which became the dominant arboreal pollen type. This shift was likely the result of a long relatively fire-free period coupled with warmer and wetter climates spanning much of the early Holocene. A brief but marked decrease in water availability around 8500-8000 cal yr BP resulted in the strong decrease of Dodonaea pollen. The vegetation of the mid- to late Holocene is characterised by the increased occurrence of Asteraceae and succulent taxa, suggesting substantially drier conditions. These data give unprecedented insight into the vegetation dynamics across a period of substantial, rapid climate change, and while they confirm the presence of fynbos elements throughout the last 15,600 years, the results highlight significant fluctuations in the vegetation that were triggered by changes in both climate and fire regimes. (C) 2013 Elsevier B.V. All rights reserved.

Structural and magnetic properties of Ni1-xZnxFe2O4 (x=0, 0.5 and 1) nanopowders prepared by sol-gel method

A series of nanostructured Ni-Zn ferrites Ni1-xZnxFe2O4 (x=0, 0.5 and 1) with a grain size from 24 to 65 nm have been prepared with a sol-gel method. The effect of composition and sintering temperature on morphology, magnetic properties, Curie temperature, specific heating rate at 295 kHz and hysteresis loss have been studied. The highest coercivity of 50 and 40 Oe, were obtained for NiFe2O4 and Ni0.5Zn0.5Fe2O4 samples with the grain size of 35 and 29 nm, respectively. The coercivity of Ni and Ni-Zn mixed ferrites decreased with temperature. The Bloch exponent was 1.5 for all samples. As the grain size increased, the Curie temperature of NiFe2O4 increased from 849 to 859 K. The highest saturation magnetization of 70 emu/g at 298 K and the highest specific heating rate of 1.6 K/s under radiofrequency heating at 295 kHz were observed over NiFe2O4 calcined at 1073 K. Both the magnitude of the hysteresis loss and the temperature dependence of the loss are influenced by the sintering temperature and composition.