Impact of Membrane Phospholipids and Exosomes on the Kinetics of Amyloid-ß Fibril Assembly.

Alzheimer's disease (AD) is linked with the self-association of the amyloid-ß peptide (Aß) into oligomers and fibrils. The brain is a lipid rich environment for Aß to assemble, while the brain membrane composition varies in an age dependent manner, we have therefore monitored the influence of lipid bilayer composition on the kinetics of Aß40 fibril assembly. Using global-fitting models of fibril formation kinetics, we show that the microscopic rate constant for primary nucleation is influenced by variations in phospholipid composition. Anionic phospholipids and particularly those with smaller headgroups shorten fibril formation lag-times, while zwitterionic phospholipids tend to extend them. Using a physiological vesicle model, we show cellular derived exosomes accelerate Aß40 and Aß42 fibril formation. Two distinct effects are observed, the presence of even small amounts of any phospholipid will impact the slope of the fibril growth curve. While subsequent additions of phospholipids only affect primary nucleation with the associated change in lag-times. Heightened anionic phospholipids and cholesterol levels are associated with aging and AD respectively, both these membrane components strongly accelerate primary nucleation during Aß assembly, making a link between disrupted lipid metabolism and Alzheimer's disease.

CYP2C19*17 association with higher plasma 4-hydroxy tamoxifen in Pakistani (estrogen-positive) breast cancer patients.

Breast cancer (BC) continues to be the most common cancer in the women worldwide. Since estrogen receptor (ER)-positive BC accounts for the majority of newly diagnosed cases, endocrine therapy is advised to utilize either tamoxifen (Tam) or aromatase inhibitors. The use of Tam as a monotherapy or in conjunction with an aromatase inhibitor following two or three years of endocrine therapy has long been recommended. When used adjuvantly, Tam medication reduces BC mortality and relapses, while it extends survival times in metastatic BC when used in conjunction with other treatments. Unfortunately, the efficiency of Tam varies considerably. This study was conducted to explore the influence of genetic polymorphisms in CYP2C19 gene on Tam's pharmacogenetics and pharmacokinetics in estrogen-positive BC patients. Data from healthy, unrelated individuals (n = 410; control group) and ER-positive BC patients (n = 430) receiving 20 mg of Tam per day were recruited. Steady-state plasma concentrations of Tam and its three metabolites were quantified using the high-performance liquid chromatography in the patients. The CYP2C19 polymorphisms were genotyped using an Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) approach. More than 65% of healthy individuals were extensive metabolizers (*1/*1) for CYP2C19, whereas more than 70% of ER-positive BC patients were rapid and ultrarapid metabolizers (*1/17*, *17/17*). The polymorphism CYP2C19*17 is significantly associated with higher 4-hydroxytamoxifen (4-OH-Tam). Patients with the *17/*17 genotype exhibited 1- to 1.5-fold higher 4-OH-Tam, which was also high in patients with the *1/*2 and *2/*2 genotypes.

Molecular Biology of Cadmium Toxicity in Saccharomyces cerevisiae.

Cadmium (Cd) is a toxic heavy metal mainly originating from industrial activities and causes environmental pollution. To better understand its toxicity and pollution remediation, we must understand the effects of Cd on living beings. Saccharomyces cerevisiae (budding yeast) is an eukaryotic unicellular model organism. It has provided much scientific knowledge about cellular and molecular biology in addition to its economic benefits. Effects associated with copper and zinc, sulfur and selenium metabolism, calcium (Ca2+) balance/signaling, and structure of phospholipids as a result of exposure to cadmium have been evaluated. In yeast as a result of cadmium stress, "mitogen-activated protein kinase," "high osmolarity glycerol," and "cell wall integrity" pathways have been reported to activate different signaling pathways. In addition, abnormalities and changes in protein structure, ribosomes, cell cycle disruption, and reactive oxygen species (ROS) following cadmium cytotoxicity have also been detailed. Moreover, the key OLE1 gene that encodes for delta-9 FA desaturase in relation to cadmium toxicity has been discussed in more detail. Keeping all these studies in mind, an attempt has been made to evaluate published cellular and molecular toxicity data related to Cd stress, and specifically published on S. cerevisiae.

Osmoregulation and its actions during the drought stress in plants.

Drought stress, which causes a decline in quality and quantity of crop yields, has become more accentuated these days due to climatic change. Serious measures need to be taken to increase the tolerance of crop plants to acute drought conditions likely to occur due to global warming. Drought stress causes many physiological and biochemical changes in plants, rendering the maintenance of osmotic adjustment highly crucial. The degree of plant resistance to drought varies with plant species and cultivars, phenological stages of the plant, and the duration of plant exposure to the stress. Osmoregulation in plants under low water potential relies on synthesis and accumulation of osmoprotectants or osmolytes such as soluble proteins, sugars, and sugar alcohols, quaternary ammonium compounds, and amino acids, like proline. This review highlights the role of osmolytes in water-stressed plants and of enzymes entailed in their metabolism. It will be useful, especially for researchers working on the development of drought-resistant crops by using the metabolic-engineering techniques.

Relationship of single nucleotide polymorphisms and haplotype interaction of mitochondrial unfolded protein response pathway genes with head and neck cancer.

Aim: In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPRmt) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. Materials & methods: The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. Results: Multivariate analysis showed that AA genotype of rs3782116 showed fivefold, GG genotype of rs6598072 approximately twofold and CC genotype of rs4946936 and TT genotype of rs12212067 showed twofold increased risk of HNC. Furthermore, haplotype analysis showed that certain haplotypes of UPRmt pathway single nucleotide polymorphisms have significant association with increased HNC risk. Conclusion: These results show that genetic aberrations in UPRmt pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.

Advanced catalytic oxidation process based on a Ti-permanganate (Mn/Ti-H+) reaction for the treatment of dye wastewater.

This article discusses the titanium (Ti)-based permanganate advanced catalytic oxidation process (ACOP) for the possible recovery of thousands of tons of dye wastewater. The heterogeneous catalyst TiO2 in the solid state employed in the liquid phase reaction mixture with dye and potassium permanganate was recovered and reused several times for reproducible results. The kinetics were examined at various operational parameters like the effect of dyes, the effect of oxidants, the amount of catalysts, and the effect of acids, temperature, and various organic and inorganic additives used in the textile industry. The kinetics of advanced oxidation and the mechanism of dye de-coloration and degradation were monitored using the Congo red (CR) dye as a model in an aqueous medium and then applied to other dyes and real dye wastewater samples. The color removal was up to 98%, with the removal efficiency being linear with the dose at a particular time. This method could exhibit the complete color removal of the dye wastewater, leading to mineralization coupled with a change in the oxidation state of Mn from +7 to +2. The method also improved the BOD/COD ratio, followed by an increase in the salinity of the recycled water. This indicated that this method can be used not only for the highly efficient de-colorization of dye wastewater but also as a preliminary step for the utilization of the dye wastewater after its recycling. The newly developed system was proven to be very cost-effective and eco-friendly with low sludge quantity, which contained numerous nitrogenous compounds, and this was validated by FTIR and HPLC analyses; thus, the system may be used in treatment plants for the recovery of wastewater.

New Prospective for Enhancement in Bioenergy Resources Through Fungal Engineering.

BACKGROUND: Lignin and cellulose, organic constituents of the plant or plant-based material not commonly used for feeding purpose are referred as Biomass. Patents suggest that this can be used as the best resource of renewable energy. Vesicular Arbuscular Mycorrhizae (VAM) fungi can play an effective role in biomass manufacturing through activated metabolism of the plant under dual symbiosis. During C acclimatization, mycorrhizal inoculated plants existent greater number of leaves with a height of plants as compared to non-mycorrhizal plants. The current article discloses the search of the natural resources for C assimilation into biomass using mycorrhizal symbiosis. METHODS: The pot experiment was conducted in the natural environment for extraction of more bioenergy through biomass of Conocarpus erectus L under VAM (Glomus fasciculatum) inoculation in various environmental conditions with replicates. RESULTS: It observed that these fungal engineered plants showed distinctive prospective to offer, enhanced biomass to energy couple with a strong network for sinking CO2 from the atmosphere via strong roots and large surface area of leaves. There was an increase in biomass (9-17% respectively) of the plant under drought-VAM, VAM inoculation and VAM- enriched CO2 conditions in same period in comparison to control plants through lignin, cellulose and carbohydrate contents. It was followed by enhanced enzyme activities and nutrient ions in dual symbiosis. CONCLUSION: Coupling biomass-originated energy may recover environmental conditions and commercial value for sustainable growth in energy consumption sector. The green energy from fungal engineered plants may replace high demand of fossil fuel as a young biofuel and make the cities more productive in the fabrication of bioenergy too in the form of biomass or biofuel with C impartial atmosphere.

Advanced oxidation of acridine orange by aqueous alkaline iodine.

The advanced oxidation process is certainly used for the dye waste water treatment. In this continuation a new advanced oxidation via aqueous alkaline iodine was developed for the oxidation of acridine orange (AO) {3, 6 -bis (dimethylamino) acridine zinc chloride double salt}. Oxidation Kinetics of AO by alkaline solution of iodine was investigated spectrophotometrically at λmax 491 nm. The reaction was monitored at various operational parameters like several concentrations of dye and iodine, pH, salt electrolyte and temperature. The initial steps of oxidation kinetics followed fractional order reaction with respect to the dye while depend upon the incremental amount of iodine to certain extent whereas maximum oxidation of AO was achieved at high pH. Decline in the reaction rate in the presence of salt electrolyte suggested the presence of oppositely charged species in the rate determining step. Kinetic data revealed that the de-colorization mechanism involves triodate (I3-) species, instead of hypoidate (OI-) and hypiodous acid (HOI), in alkaline medium during the photo-excitation of hydrolyzed AO. Alleviated concentration of alkali result in decreasing of rate of reaction, clearly indicate that the iodine species are active oxidizing species instead of OH radical. Activation parameters at elevated temperatures were determined which revealed that highly solvated state of dye complex existed into solution. Reaction mixture was subjected to UV/Visible and GC mass spectrum analysis that proves the secondary consecutive reaction was operative in rate determining step and finally dye complex end into smaller fragments.