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Forest decline is the interactive result of factors such as climate, in particular the occurrence of drought and early frost, tree age, habitat quality, pests and diseases, and the phenomenon of dust. The aim of this study was 1) to measure the amount of dust particles deposited on Brant's oak (Quercus brantii Lindl.) trees in a forest stand in Ilam province and 2) to survey the biological characteristics of healthy trees and those hosting oak charcoal disease. Random sampling was performed from different parts of the crown of each rootstock to measure biochemical traits, study of antioxidant activity and enzymes and amount of dry dust deposition on the leaf. On the leaves, samples were randomly drawn from different parts of the crown. The average dry deposited dust per unit leaf area of oak during the three sampling periods ranged from 0.21 to 0.26 mg/cm². No significant difference was observed between healthy and diseased trees. The amount of chlorophyll a, b, total and carotenoids in healthy and diseased trees were significantly different, with observed 0.3, 0.06, 0.1 and 0.14 mg/g fresh weight in healthy trees, as well as over 0.038, 0.05, 0.08 and 0.12 mg/g fresh weight in diseased trees, respectively. In addition, the amount of antioxidants and catalase in healthy trees were 56.9 percent and 0.01 units per mg of protein, respectively, which were significantly higher than the diseased trees showing 42.8 and 0.008 units per mg of protein. The amount of phenol and flavonoids in diseased trees (169.9 and 47.8 mg/g fresh weight) was more than healthy trees (114.5 and 36.6 mg/g fresh weight). This study concludes that Brant's oak in the studied forest is very resistant to coal disease, added by its high ability to preserve and retain dust particles. [ABSTRACT FROM AUTHOR]

Inhibitors of the transforming growth factor-β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-β-binding proteins (LTBPs) present TGF-β1 in the extracellular matrix, and TGF-β1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-β1 presented by LTBPs but did not bind to TGF-β1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-β1 that is not accessible on GARP- or LRRC33-presented TGF-β1, explaining the antibody's selectivity for LTBP-complexed TGF-β1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-β1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-β inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-β1 as an approach for treating fibrosis.

Background: Purslane seed oil, as a potential nutritious source of omega-3 fatty acid, is susceptible to oxidation. Encapsulation in yeast cells is a possible approach for overcoming this problem. In the present study, purslane seed oil was encapsulated in non-plasmolysed, plasmolysed and plasmolysed carboxy methyl cellulose (CMC)-coated Saccharomyces cerevisiae cells and measurements of oil loading capacity (LC), encapsulation efficiency (EE), oxidative stability and the fatty acid composition of oil-loaded microcapsules were made. Furthermore, investigations of morphology and thermal behavior, as well as a Fourier transform-infrared (FTIR) analyses of microcapsules, were performed., Results: The values of EE, LC were approximately 53-65% and 187-231 g kg -1 , respectively. Studies found that the plasmolysis treatment increased EE and LC and decreased the mean peroxide value (PV) of microencapsulated oil. The presence of purslane seed oil in yeast microcapsules was confirmed by FTIR spectroscopy and differential scanning calorimetry analyses. The lowest rate of oxidation belonged to the oil-loaded plasmolysed CMC-coated microcapsules (16.73 meqvO 2 kg -1 ), whereas the highest amount of oxidation regardless of native oil referred to the oil-loaded in non-plasmolysed cells (28.15 meqvO 2 kg -1 )., Conclusion: The encapsulation of purslane seed oil in the yeast cells of S. cerevisiae can be considered as an efficient approach for extending the oxidative stability of this nutritious oil and facilitating its application in food products. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

Pharmacological administration of FGF21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. Here we report the design, optimization, and characterization of a long acting glyco-variant of FGF21. Using a combination of N-glycan engineering for enhanced protease resistance and improved solubility, Fc fusion for further half-life extension, and a single point mutation for improving manufacturability in Chinese Hamster Ovary cells, we created a novel FGF21 analogue, Fc-FGF21[R19V][N171] or PF-06645849, with substantially improved solubility and stability profile that is compatible with subcutaneous (SC) administration. In particular, it showed a low systemic clearance (0.243 mL/hr/kg) and long terminal half-life (~200 hours for intact protein) in cynomolgus monkeys that approaches those of monoclonal antibodies. Furthermore, the superior PK properties translated into robust improvement in glucose tolerance and the effects lasted 14 days post single SC dose in ob/ob mice. PF-06645849 also caused greater body weight loss in DIO mice at lower and less frequent SC doses, compared to previous FGF21 analogue PF-05231023. In summary, the overall PK/PD and pharmaceutical profile of PF-06645849 offers great potential for development as weekly to twice-monthly SC administered therapeutic for chronic treatment of metabolic diseases.

A large body of data exists demonstrating that neonatal Fc receptor (FcRn) binding of an IgG via its Fc CH2-CH3 interface trends with the pharmacokinetics (PK) of IgG. We have observed that PK of IgG molecules vary widely, even when they share identical Fc domains. This led us to hypothesize that domains distal from the Fc could contribute to FcRn binding and affect PK. In this study, we explored the role of these IgG domains in altering the affinity between IgG and FcRn. Using a surface plasmon resonance-based assay developed to examine the steady-state binding affinity (K D ) of IgG molecules to FcRn, we dissected the contributions of IgG domains in modulating the affinity between FcRn and IgG. Through analysis of a broad collection of therapeutic antibodies containing more than 50 unique IgG molecules, we demonstrated that variable domains, and in particular complementarity-determining regions (CDRs), significantly alter binding affinity to FcRn in vitro. Furthermore, a panel of IgG molecules differing only by 1-5 mutations in CDRs altered binding affinity to FcRn in vitro, by up to 79-fold, and the affinity values correlated with calculated isoelectric point values of both variable domains and CDR-L3. In addition, tighter affinity values trend with faster in vivo clearance of a set of IgG molecules differing only by 1-3 mutations in human FcRn transgenic mice. Understanding the role of CDRs in modulation of IgG affinity to FcRn in vitro and their effect on PK of IgG may have far-reaching implications in the optimization of IgG therapeutics.

Purslane seed oil could be considered as potential nutritious oil due to its desirable fatty acid composition and other biological active compounds. In this study the effect of three extraction procedure including solvent extraction, cold pressing and microwave pretreatment (MW) followed by cold pressing on oil yield, physicochemical properties, oxidative stability and rheological behaviors of oil was investigated. Solvent extracted oil had the highest extraction yield (72.31%). Pretreatment by microwave before cold press extraction resulted in an increase in extraction yield, total phenolic compound (TPC) and antioxidant activity. Cold press extracted oil had the lowest oxidative stability (4.64h). This property was greatly enhanced by microwave irradiation, so that the longest oxidative stability was found in MW-cold press extracted oil with 9.67h. Furthermore, all extracted oils demonstrated Newtonian flow behaviors. MW-cold press extracted oil had the greatest apparent viscosity and highest sensitivity to temperature changes (E a =29.18kJ/mol -1 )., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: One of the natural phenomena which have had considerable impacts on various regions of the world, including Iran, is "dust storm". In recent years, this phenomenon has taken on new dimensions in Iran and has changed from a local problem to a national issue. This study is an attempt to investigate the formation of the dust storms crossing the Western Iran., Methodology: To find the sources of the dust storms entering Iran, first we examine three determined dust paths in the region and their temporal activities, using MODIS satellite images. Then, four regions were identified as dust sources through soil, land cover and wind data. Finally, atmospheric analyses are implemented to find synoptic patterns inducing dust storms., Results and Discussion: Source 1 has covered the region between the eastern banks of Euphrates and western banks of Tigris. Source 2 is in desert area of western and south-western Iraq. Finally source 3 is bounded in eastern and south-eastern deserts of Saudi Arabia called Rub-Al-Khali desert, or Empty Quarter. Moreover, south-eastern part of Iraq (source 4) was also determined as a secondary source which thickens the dust masses originating from the above mentioned sources. The study of synoptic circulations suggests that the dust storms originating from source 1 are formed due to the intense pressure gradient between the low-pressure system of Zagros and a high-pressure cell formed on Mediterranean Sea. The dust events in sources 2 and 3 are outcomes of the atmospheric circulations dominant in the cold period of the year in mid-latitudes.

Purpose: To assess the application of succinimidyl iodobenzoate (SIB) iodination method in labeling biotherapeutics to study their pharmacokinetics (PK) and biodistribution., Method: An IgG molecule (protein-01) and a 40 KDa protein (protein-02) were evaluated. Pharmacokinetics (PK) and biodistribution of the radiolabeled IgG ((125)I-protein-01) in mice compared parameters from SIB and Iodogen protein iodination labeling methods. In addition, PK of radiolabeled 40 KDa protein ((125)I-protein-02) using SIB was compared with non-labeled protein-02 analyzed by ligand binding assay (LBA)., Results: Up to 72 h following a single IP injection to mice, the percentage of "free-label" determined by the soluble counts after TCA precipitation to total radioactivity in serum samples was 2.8-49.4% vs. <1.0% for (125)I-protein-01 iodinated via Iodogen or SIB methods, respectively, suggesting a higher in vivo stability of (125)I-protein-01 labeled via the SIB method. The serum exposure of (125)I-protein-01 was two-fold higher, and correspondingly, the tissue exposure was also higher (averaging 3.6 fold at 168 h) when using SIB protein labeling method than when using the Iodogen method. In addition, following subcutaneous (SC) administration to mice, the serum exposure of (125)I-protein-02 labeled via SIB method was similar to protein-02 measure by LBA., Conclusion: In this study, iodination of proteins using SIB methodology has overcome the dehalogenation problem in vivo which is inherent in Iodogen method, and PK parameters of a protein iodinated via SIB were comparable to the un-labeled protein measured by LBA. The SIB iodination method is an improved labeling approach for biotherapeutics used in studying PK and biodistribution characteristics.

A comparison of four different ligand-binding assay technology platforms (ELISA, Meso Scale Discovery®, Gyros® and AlphaLISA®) was conducted using quantitative assays for the measurement of a human IgG₁ monoclonal antibody (MAb) in rat serum. The assays used common reagents for Fc-specific measurement to determine total levels of a human IgG MAb drug analyte, and all were fully optimized for use on each platform. Mock MAb study samples were prepared and analyzed using all platforms to assess assay performance. Assay parameters such as sensitivity, dynamic range, minimum required dilution and sample volume as well as other considerations such as per-run cost, technology availability, requisite equipment and necessary reagent modifications were evaluated toward the determination of a default go-to assay platform for monoclonal antibody biotherapeutics in this laboratory. Based primarily on superior assay performance, Meso Scale Discovery and Gyros were selected from the four technologies evaluated as our default platforms for non-regulated (discovery) study support. As an adjunct, immunoaffinity LC-MS/MS was explored as an alternate platform for generic Fc quantitation and was found to perform similarly to the ligand-binding assays., (© 2013. Published by Elsevier B.V. All rights reserved.)