Study of curcumin behavior in two different lipid bilayer models of liposomal curcumin using molecular dynamics simulation

Liposomal formulation of curcumin is an important therapeutic agent for the treatment of various cancers. Despite extensive studies on the biological effects of this formulation in cancer treatment, much remains unknown about curcumin–liposome interactions. Understanding how different lipid bilayers respond to curcumin molecule may help us to design more effective liposomal curcumin. Here, we used molecular dynamics simulation method to investigate the behavior of curcumin in two lipid bilayers commonly used in preparation of liposomal curcumin, namely dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylglycerol (DMPG). First, the free energy barriers for translocation of one curcumin molecule from water to the lipid bilayer were determined by using the potential of mean force (PMF). The computed free energy profile exhibits a global minimum at the solvent–headgroup interface (LH region) for both lipid membranes. We also evaluated the free energy difference between the equilibrium position of curcumin in the lipid bilayer and bulk water as the excess chemical potential. Our results show that curcumin has the higher affinity in DMPG compared to DPPC lipid bilayer (?8.39 vs. ?1.69 k_BT) and this is related to more hydrogen bond possibility for curcumin in DMPG lipid membrane. Next, using an unconstrained molecular dynamic simulation with curcumin initially positioned at the center of lipid bilayer, we studied various properties of each lipid bilayer system in the presence of curcumin molecule that was in full agreement with PMF and experimental data. The results of these simulation studies suggest that membrane composition could have a large effect on interaction of curcumin–lipid bilayer.     

One-step isolation of plasma membrane proteins using magnetic beads with immobilized concanavalin A

We have developed a simple method for isolating and purifying plasma membrane proteins from various cell types. This one-step affinity-chromatography method uses the property of the lectin concanavalin A (ConA) and the technique of magnetic bead separation to obtain highly purified plasma membrane proteins from crude membrane preparations or cell lines. ConA is immobilized onto magnetic beads by binding biotinylated ConA to streptavidin magnetic beads. When these ConA magnetic beads were used to enrich plasma membranes from a crude membrane preparation, this procedure resulted in 3.7-fold enrichment of plasma membrane marker 5′-nucleotidase activity with 70% recovery of the activity in the crude membrane fraction of rat liver. In agreement with the results of 5′-nucleotidase activity, immunoblotting with antibodies specific for a rat liver plasma membrane protein, CEACAM1, indicated that CEACAM1 was enriched about threefold relative to that of the original membranes. In similar experiments, this method produced 13-fold enrichment of 5′-nucleotidase activity with 45% recovery of the activity from a total cell lysate of PC-3 cells and 7.1-fold enrichment of 5′-nucleotidase activity with 33% recovery of the activity from a total cell lysate of HeLa cells. These results suggest that this one-step purification method can be used to isolate total plasma membrane proteins from tissue or cells for the identification of membrane biomarkers.     

Optimization of date syrup as a novel medium for lovastatin production by <Emphasis Type="Italic">Aspergillus terreus</Emphasis> ATCC 20542 and analyzing assimilation kinetic of carbohydrates

Lovastatin is a statin drug, which lowers cholesterol level in blood due to inhibition of (S)-3-hydroxy-3-methylglutaryl-CoA reductase. Date syrup is a rich medium for microbial growth and metabolite production. The main carbohydrates present in the date syrup are glucose and fructose. In this study, date syrup was used as a complex and bioresource medium for lovastatin production by Aspergillus terreus in the submerged cultivation. Optimization of the date syrup medium in order to achieve the highest titers of lovastatin and biomass was carried out. Four factors were studied by response surface methodology including concentration of date syrup carbohydrates, yeast extract concentration, pH, and rotation speed of the shaker. Optimal conditions for these factors found were as follows: concentration of date syrup carbohydrates, 64 g/l; yeast extract concentration, 15 g/l; pH, 6.5; and agitation speed, 150 rpm. It gave lovastatin concentration of 105.6 mg/l. Next, batch cultures in the optimal conditions were performed in a 2.5-l working volume bioreactor and led to the lovastatin titer of 241.1 mg/l during 12 days. Aspergillus terreus showed diauxic growth in the optimized medium with a shift from glucose to fructose assimilation during the run. Glucose and fructose assimilation kinetic parameters revealed that more lovastatin is produced during glucose assimilation, while more biomass was formed during fructose assimilation.     

Climate change,unpredictable cold waves and possible brakes on plant migration

Aim Increases in annual mean temperature in the course of current climate change are expected to facilitate mass species migration towards higher altitudes and latitudes. However, this migration may be slowed, or even temporarily reversed, by infrequent and unpredictable episodes of low winter temperatures. Iran experienced a severe cold wave in January and February 2008, giving an opportunity to observe the effects on a large number of woody plant species, many growing further north than their natural ranges. Location The study was carried out in the National Botanical Garden of Iran (35°44′20.06″ N; 51°10′25.66″ E). Method To estimate the damage caused to each individual woody plant in the garden, we adopted the following protocol; at the start of the growing season, at the end of March and beginning of April 2008, all woody species were inspected for damage. In the case of evergreens this took the form of obvious damage to foliage, usually manifested as severe browning. In the case of deciduous species, damage was recognized by the failure of all or part of the plant to produce new leaves; all affected individual plants were labelled. In July all labelled plants were rechecked and, based on whole or partial above‐ground die‐back, a final list of damaged individuals was produced. Results As expected, the majority of native and exotic species introduced from cold temperate habitats showed no freezing injuries. Many woody species in the garden were damaged or killed, despite their previous survival and growth, in many cases for up to 40 years. The majority of taxa (101 out of a total of 145) that suffered freezing‐induced damage were evergreens. Main conclusions The results indicate that despite an increase in mean annual temperature, unpredictable lethal cold waves may retard the expansion of plants towards higher altitudes and latitudes. Broadleaved evergreen species from warm climates were particularly badly affected, with many species suffering high rates of mortality.     

Relationships between environmental variables and vegetation across mountain wetland sites,N. Iran

The mountain wetlands studied represent a unique habitat on the southern slopes of the Alborz mountain range, the second largest range in Iran. In comparison with other parts of this range the western section is ecologically and botanically unknown. Floristic and vegetation variation were assessed using diverse environmental variables along a broad altitudinal span (350 m to 3200 m a.s.l.). Using both statistical and ordination analyses floristic variation was assessed on three defined altitudinal belts which were delimited based on Alborz macro-climatic boundaries. The distribution of individual wetland plant species, of phytogeographic elements and of life-forms all differ among altitudinal belts. This result is also shown in both direct and indirect analyses of ordinations. The proportion of geophytes significantly increases with altitude and geophytes are very well represented in the upper altitudinal belt. The number of species of a narrow phytogeographical distribution (e.g. endemics) increases with altitude, soil pH and EC declined with altitude. The first axis of DCA ordination with passively projected environmental variables indicates that, organic matter and concentration of Fe²⁺ are increased toward higher altitude. The second axis of ordination is related to both soil texture and slope inclination. The distribution of species in the CCA species plot is also close to the distribution of those in the DCA ordination. This study indicates that altitude and slope together with other dependent environmental variables (pH, EC, Ca²⁺ and soil texture) are the main ecological factors controlling species distribution across the Western Alborz wetland sites.     

Galaxy-ML: An accessible,reproducible, and scalable machine learning toolkit for biomedicine

Supervised machine learning is an essential but difficult to use approach in biomedical data analysis. The Galaxy-ML toolkit (https://galaxyproject.org/community/machine-learning/) makes supervised machine learning more accessible to biomedical scientists by enabling them to perform end-to-end reproducible machine learning analyses at large scale using only a web browser. Galaxy-ML extends Galaxy (https://galaxyproject.org), a biomedical computational workbench used by tens of thousands of scientists across the world, with a suite of tools for all aspects of supervised machine learning.

This is a PLOS Computational Biology Software paper.

     

Immobilization of acetylcholinesterase in nanofibrous PVA/BSA membranes by electrospinning

Electrospinning, a simple and versatile method to fabricate nanofibrous supports, has attracted continuous attention in the field of enzyme immobilization. In this study, acetylcholinesterase (AChE) has been successfully immobilized in PVA nanofibers via electrospinning of a mixture of AChE, BSA as an enzyme stabilizing additive and PVA. The maximum activity recovery of immobilized AChE was about 40%. In comparison with free enzyme, the immobilized AChE showed improved stability while retaining a considerable amount of activity at lower pH values. Moreover, the immobilized AChE retained >34% of its initial activity when stored at 30°C for 100 days and retained 70% of its initial activity after ten consecutive reactor batch cycles.