Anti-idiotypic monoclonal antibody to a T-cell chronic lymphatic leukemia

Summary A murine anti-idiotypic monoclonal antibody (mAb), F1, (IgG_2a) was produced against the variable part of the T-cell receptor for antigen (T_i, /) on the tumor cells of a patient with T-cell chronic lymphatic leukemia (CD3⁺, 8⁺, 4^–). The molecular weight of the protein reactive with mAb F1, comodulation and coprecipitation with anti-CD3 antibody, and the restricted tumor-cell reactivity strongly support the anti-idiotypic nature of mAb F1. MAb F1 also stained 4% of peripheral blood lymphocytes of healthy donors. MAb F1 did not stimulate the tumor cells to DNA synthesis, but stimulated a fraction of the normal peripheral blood lymphocytes, mAb F1 did not mediate antibody-dependent cellular cytotoxicity or complement lysis to any significant degree in vitro. Three infusions of 1–10 mg anti-idiotypic mAb were given over a period of 4 weeks. The plasma half-life for mAb F1 was 3 h in the first 2 h after infusion and 44 h from 2 h to 120 h after infusion. After each treatment a rapid decrease of circulating tumor cells was seen. During the observation period an 80% reduction of the total circulating tumor cells was noted. After the second infusion, IgM and IgG antimouse antibodies were detected. Side-effects from therapy were fever, chills, nausea, vomiting, diarrhea, tachycardia, increase in systolic blood pressure and shortness of breath. Thus, in T-cell malignancies a major reduction of circulating tumor cells can be accomplished by low doses of anti-idiotypic mAb. Anti-idiotypic mAb might be a therapeutic agent of significant importance.     

Exogenous proline significantly affects the plant growth and nitrogen assimilation enzymes activities in rice (<Emphasis Type="Italic">Oryza sativa</Emphasis>) under salt stress

Salinity has been shown to be a major factor contributing to low nitrogen availability in plants. To verify the changes in nitrogen metabolism activity as affected by the exogenous application of proline under salt stress and its relation to salt tolerance, in vitro rice shoot apices were used as a model to study the growth performance and changes in nitrogen assimilation activities in two Malaysian rice cultivars MR 220 and MR 253. Results revealed that salt stress greatly reduced the plant height, shoot nitrate (NO₃ ^?) content, shoot glutamine synthetase (GS), and root nitrate reductase (NR) activities in both cultivars. Supplementation of proline significantly increased the plant height, number of roots, root NO₃ ^? content, root NR, and root GS activities under salt stress in both cultivars with greater enhancement in MR 253 than MR 220. The results also indicated that MR 253 possessed higher nitrite reductase (NiR) and glutamate synthase (NADH–GOGAT) activities as compared with MR 220 in all tested treatments. It was suggested that the NO₃ ^? content, NR, and GS activities played important roles in regulating nitrogen metabolism under salt stress. Taken together, it was concluded that the ability of proline in mitigating salt stress-induced damages was correlated with the changes in nitrogen assimilation activities.     

Modelling and simulation of mutant alleles of breast cancer metastasis suppressor 1 (BRMS1) gene

Computational tools occupy the prime position in the analysis of large volume of post-genomic data. These tools have advantage over the wet lab experiments in terms of high coverage, cost and time. Breast cancer is the most common cancer in females worldwide. It is a genetically heterogeneous disorder and many genes are involved in the pathway of the disease. Mutations in metastasis suppressor gene are the major cause of the disease. In this study, the effects of mutations in breast cancer metastasis suppressor 1gene upon protein structure and function were examined by means of computational tools and information from databases.This study can be useful to predict the potential effect of every allelic variant, devise new biological experiments and to interpret and predict the patho-physiological impact of new mutations or non-synonymous polymorphisms.     

Physical and chemical mutagens improved Sporotrichum thermophile,strain ST20 for enhanced Phytase activity

ObjectivePhosphorous is an essential micronutrient of plants and involved in critical biological functions. In nature, phosphorous is mostly present in immobilized inorganic mineral and in the fixed organic form including phytic acid and phosphoesteric compounds. However, the bioavailability of bound phosphorous could be enhanced by the use of phosphate solubilizing microorganisms such as bacteria and fungi. The phytases are widespread in an environment and have been isolated from different sources comprising bacteria and fungi.MethodologyIn current studies, we show the successful use of gamma rays and EMS (Ethyl Methane Sulphonate) mutagenesis for enhanced activity of phytases in a fungal strain Sporotrichum thermophile.ResultsWe report an improved strain ST2 that could produce a clear halo zone around the colony, up to 24 mm. The maximum enzymatic activity was found of 382 U/mL on pH 5.5. However, the phytase activity was improved to 387 U/ml at 45 °C. We also report that the mutants produced through EMS showed the greater potential for phytase production.ConclusionThe current study highlights the potential of EMS mutagenesis for strain improvement over physical mutagens.     

Pyrolysis of Mixed Date Stones and Pistachio Shells: Identification of Bio-Oil and Utilization of Bio-Char as Activated Carbon Precursor

Thermal pyrolysis of mixed date stones and pistachio shells in a semi-batch reactor was addressed in this study. The highest yield of liquids (51.20 %) was produced at 500 °C, 90 min, 20 °C/min heating rate, and 50 mesh particle size. Under these conditions, yield of liquid from date stones and pistachio shells separately was 49.12 % and 47.67 %, respectively. The FT-IR results confirmed the presence of multiple oxygen-containing compounds in the bio-oil. Results from GC–MS declared that it was predominately composed of acids (57.57 %), esters (21.35 %), phenols (4.63 5), and alcohols (3.49 5). The obtained biochar was transformed into activated carbon (AC) by the optimized ZnCl₂ activation method. The ideal AC was synthesized at 600 °C for 60 min using a 2 : 1 ZnCl₂: biochar impregnation ratio. FESEM and XRD measurements showed that the AC was amorphous. The prepared AC was effective in eliminating dibenzothiophene (DBT) from model fuel (200 ppm DBT/hexane) with a maximum performance 95.26 % at 40 °C for 1h using 0.35 g of the AC. The exhausted AC was regenerated and reutilized 4 times, and removal efficiency reached 88.23 % in the 4^th cycle under ideal working conditions.     

16.1% Efficient Hysteresis‐Free Mesostructured Perovskite Solar Cells Based on Synergistically Improved ZnO Nanorod Arrays

Significant efficiency improvements are reported in mesoscopic perovskite solar cells based on the development of a low‐temperature solution‐processed ZnO nanorod (NR) array exhibiting higher NR aspect ratio, enhanced electron density, and substantially reduced work function than conventional ZnO NRs. These features synergistically result in hysteresis‐free, scan‐independent, and stabilized devices with an efficiency of 16.1%. Electron‐rich, nitrogen‐doped ZnO (N:ZnO) NR‐based electron transporting materials (ETMs) with enhanced electron mobility produced using ammonium acetate show consistently higher efficiencies by one to three power points than undoped ZnO NRs. Additionally, the preferential electrostatic interaction between the ­nonpolar facets of N:ZnO and the conjugated polyelectrolyte polyethylenimine (PEI) has been relied on to promote the hydrothermal growth of high aspect ratio NR arrays and substantially improve the infiltration of the perovskite light absorber into the ETM. Using the same interactions, a conformal PEI coating on the electron‐rich high aspect ratio N:ZnO NR arrays is ­successfully applied, resulting in a favorable work function shift and altogether leading to the significant boost in efficiency from <10% up to >16%. These results largely surpass the state‐of‐the‐art PCE of ZnO‐based perovskite solar cells and highlight the benefits of synergistically combining mesoscale control with doping and surface modification.     

Cloning, characterization and molecular docking of a highly thermostable β-1,4-glucosidase from Thermotoga petrophila

A genomic DNA fragment, encoding a thermotolerant β-glucosidase, of the obligate anaerobe Thermotoga petrophila RKU-1 was cloned after PCR amplification into Escherichia coli strain BL21 CodonPlus. The purified cloned enzyme was a monomeric, 51.5?kDa protein (by SDS-PAGE) encoded by 1.341?kb gene. The estimated K (m) and V (max) values against p-nitrophenyl-β-D-glucopyranoside were 2.8?mM and 42.7?mmol?min(-1)?mg(-1), respectively. The enzyme was also active against other p-nitrophenyl substrates. Possible catalytic sites involved in hydrolyzing different p-nitrophenyl substrates are proposed based on docking studies of enzyme with its substrates. Because of its unique characters, this enzyme is a potential candidate for industrial applications.     

Ezetimibe ameliorates intestinal chylomicron overproduction and improves glucose tolerance in a diet-induced hamster model of insulin resistance

Ezetimibe is a cholesterol uptake inhibitor that targets the Niemann-Pick C1-like 1 cholesterol transporter. Ezetimibe treatment has been shown to cause significant decreases in plasma cholesterol levels in patients with hypercholesterolemia and familial hypercholesterolemia. A recent study in humans has shown that ezetimibe can decrease the release of atherogenic postprandial intestinal lipoproteins. In the present study, we evaluated the mechanisms by which ezetimibe treatment can lower postprandial apoB48-containing chylomicron particles, using a hyperlipidemic and insulin-resistant hamster model fed a diet rich in fructose and fat (the FF diet) and fructose, fat, and cholesterol (the FFC diet). Male Syrian Golden hamsters were fed either chow or the FF or FFC diet ± ezetimibe for 2 wk. After 2 wk, chylomicron production was assessed following intravenous triton infusion. Tissues were then collected and analyzed for protein and mRNA content. FFC-fed hamsters treated with ezetimibe showed improved glucose tolerance, decreased fasting insulin levels, and markedly reduced circulating levels of TG and cholesterol in both the LDL and VLDL fractions. Examination of triglyceride (TG)-rich lipoprotein (TRL) fractions showed that ezetimibe treatment reduced postprandial cholesterol content in TRL lipoproteins as well as reducing apoB48 content. Although ezetimibe did not decrease TRL-TG levels in FFC hamsters, ezetimibe treatment in FF hamsters resulted in decreases in TRL-TG. Jejunal apoB48 protein expression was lower in ezetimibe-treated hamsters. Reductions in jejunal protein levels of scavenger receptor type B-1 (SRB-1) and fatty acid transport protein 4 were also observed. In addition, ezetimibe-treated hamsters showed significantly lower jejunal mRNA expression of a number of genes involved in lipid synthesis and transport, including srebp-1c, sr-b1, ppar-γ, and abcg1. These data suggest that treatment with ezetimibe not only inhibits cholesterol uptake, but may also alter intestinal function to promote improved handling of dietary lipids and reduced chylomicron production. These, in turn, promote decreases in fasting and postprandial lipid levels and improvements in glucose homeostasis.