Synthesis and immunomodulatory properties of selected oxazolone derivatives

Eleven oxazolone derivatives were synthesized and characterized by (1)H NMR, EI, IR and UV spectroscopic and CHN analysis. Three compounds, 4-[(E)-(4-nitrophenyl)methylidene]-2-phenyl-1,3-oxazol-5(4H)-one (11), 4-[(E)-(4-methoxyphenyl)methylidene]-2-methyl-1,3-oxazol-5-one (12) and 4-[(E)-(4-nitrophenyl)methylidene]-2-methyl-1,3-oxazol-5(4H)-one (13) were screened for phagocyte chemiluminescence, neutrophil chemotaxis, T-cell proliferation, cytokine production from mononuclear cells and cytotoxicity. 4-[(E)-(4-Nitrophenyl)methylidene]-2-methyl-1,3-oxazol-5(4H)-one (13) was found to be the most potent immunomodulator in the series.     

Large‐scale comparison of protein essential dynamics from molecular dynamics simulations and coarse‐grained normal mode analyses

A large‐scale comparison of essential dynamics (ED) modes from molecular dynamic simulations and normal modes from coarse‐grained normal mode methods (CGNM) was performed on a dataset of 335 proteins. As CGNM methods, the elastic network model (ENM) and the rigid cluster normal mode analysis (RCNMA) were used. Low‐frequency normal modes from ENM correlate very well with ED modes in terms of directions of motions and relative amplitudes of motions. Notably, a similar performance was found if normal modes from RCNMA were used, despite a higher level of coarse graining. On average, the space spanned by the first quarter of ENM modes describes 84% of the space spanned by the five ED modes. Furthermore, no prominent differences for ED and CGNM modes among different protein structure classes (CATH classification) were found. This demonstrates the general potential of CGNM approaches for describing intrinsic motions of proteins with little computational cost. For selected cases, CGNM modes were found to be more robust among proteins that have the same topology or are of the same homologous superfamily than ED modes. In view of recent evidence regarding evolutionary conservation of vibrational dynamics, this suggests that ED modes, in some cases, might not be representative of the underlying dynamics that are characteristic of a whole family, probably due to insufficient sampling of some of the family members by MD. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

Localized cysteine sulfenic acid formation by vascular endothelial growth factor: role in endothelial cell migration and angiogenesis

Reactive oxygen species (ROS) are important mediators for VEGF receptor 2 (VEGFR2) signalling involved in angiogenesis. The initial product of Cys oxidation, cysteine sulfenic acid (Cys-OH), is a key intermediate in redox signal transduction; however, its role in VEGF signalling is unknown. We have previously demonstrated IQGAP1 as a VEGFR2 binding scaffold protein involved in ROS-dependent EC migration and post-ischemic angiogenesis. Using a biotin-labelled Cys-OH trapping reagent, we show that VEGF increases protein-Cys-OH formation at the lamellipodial leading edge where it co-localizes with NADPH oxidase and IQGAP1 in migrating ECs, which is prevented by IQGAP1 siRNA or trapping of Cys-OH with dimedone. VEGF increases IQGAP1-Cys-OH formation, which is prevented by N-acetyl cysteine or dimedone, which inhibits VEGF-induced EC migration and capillary network formation. In vivo, hindlimb ischemia in mice increases Cys-OH formation in small vessels and IQGAP1 in ischemic tissues. In summary, VEGF stimulates localized formation of Cys-OH-IQGAP1 at the leading edge, thereby promoting directional EC migration, which may contribute to post-natal angiogenesis in vivo. Thus, targeting Cys-oxidized proteins at specific compartments may be the potential therapeutic strategy for various angiogenesis-dependent diseases.     

Sugar beet extract acts as a natural bio-stimulant for physio-biochemical attributes in water stressed wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

The present study investigated the role of sugar beet extract (SBE) as a bio-stimulant to ameliorate the adverse effects of drought on seed germination and growth of wheat (Triticum aestivum L.). Different concentrations of SBE (0, 10, 20, 30, 40 and 50%) were used for priming the wheat seeds. The experiment was conducted in laboratory (PEG-8000 was used to create water stress) as well as under natural environmental conditions (using soil with 100 and 60% field capacity). Significant ameliorating effects of seed priming with SBE were recorded on different germination attributes, i.e., time to 50% emergence (E₅₀), germination index (GI), mean emergence time (MET), germination percentage (G%), coefficient of uniformity of emergence (CUE) and germination energy (GE) under water stress. Without priming, the plants exhibited symptoms of water stress like decreased biomass, reduction in photosynthetic pigments, e.g., chlorophyll, carotenoids. Seed pre-conditioning with SBE improved the plant growth, photosynthetic pigments, antioxidants’ activities and nutrient homeostasis of plants facing water deficit and grown under well-watered conditions. The maximum increase in biomass, content of chlorophyll, carotenoids and activities of superoxide dismutase (SOD) and peroxidase (POD) was 13.4, 8.5, 11.9, 7.6, 13.6, 42.0, 19.8%, respectively, with SBE seed priming under water stress. In conclusion, SBE seed priming effectively reduced the negativities of water stress on seed germination which resulted in better plant growth in terms of enhanced biomass, photosynthetic pigments, antioxidant defense mechanism and better nutrient homeostasis. Overall, the findings suggest that seed pre-conditioning with SBE as a bio-stimulant will be helpful for better crop stand establishment under low field capacity, especially in semi-arid and arid agricultural fields.     

Impact of variants on type-2 diabetes risk genes identified through genomewide association studies in polycystic ovary syndrome: a case–control study

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females, and is associated with altered metabolic processes in particular insulin resistance and diabetes mellitus. PCOS shares with type-2 diabetes (T2D) a number of features, including beta cell dysfunction, impaired glucose tolerance and dyslipidaemia. Recently, genomewide association studies (GWAS) have reported a number of genes with reproducible associations and susceptibilities to T2D. To address this, we examined the association between the T2D GWAS candidate genes (CDKAL1, CDKN2B, COL8A1, HHEX, IGF2BP2, KCNJ1, KCNQ1 and SLC30A8) and PCOS in Saudi women. A case–control study, includes 162 cases and 162 controls was enrolled. Genotyping was carried out by the allelic discrimination method. Our results showed that the variants including rs792837 of COL8A1, rs61873498 of KCNQ1 and rs13266634 of SLC30A8 genes to be significantly more frequent in PCOS patients than in controls. Our results suggest that COL8A1, KCNQ1 and SLC30A8, which are previously identified through GWAS as T2D-associated genes, are associated with PCOS.     

Review on antibacterial characteristics of bridge engineering biomaterials

This review summarizes the research on timber construction materials used in bridge construction. It focuses on the application of antiseptic treatments and the use of timber engineering materials in decks and bridges. This review also provides an overview on the future research and prospects of engineered timber materials.     

Comparison of cold resistance physiological and biochemical features of four Herba Rhodiola seedlings under low temperature

To discuss the cold resistance performance of different Herba Rhodiolae and successfully transplant Herba Rhodiolae to the Gansu plateau area for nursing, domestication and planting, this paper systematically studies six physiological and biochemical features of Rhodiola kirilowii, Rhodiola algida, Rhodiola crenulata and Herba Rhodiolae that are closely associated with cold resistance features and concludes with the cold resistance capability of Rhodiola kirilowii. In the selected six main indexes of the Herba Rhodiolae, the POD, SOD and CAT activity and MDA and Pro content in the leaf are the main physiological and biochemical indexes to indicate the cold resistance performance of four Herba Rhodiolae seedlings and can be regarded as the preliminary indexes to assess the winter performance of Herba Rhodiolae. The research work will provide the theoretical basis for the wild variants of Herba Rhodiolae and GAPJ base construction.     

The effects of immunosuppression on regulatory CD4(+)CD25(+) T cells: impact on immunosuppression selection in transplantation

During immune response and T-cell activation, both effector T cells and regulatory T(T(reg)) cells are activated and regulated simultaneously by both positive and negative pathways. CD4(+)CD25(+) T(reg) cells play a critical role in immune tolerance to self antigens as well as to allografts in some transplant settings. Effective immunosuppressive regimens significantly reduced the incidence of acute allograft rejection in patients following organ transplantation. However, the impact of immunosuppressive treatment on the potential induction of transplant tolerance has not been well determined. In this review we summarize the effects of immunosuppressive reagents on CD4(+)CD25(+) T(reg) cells in order to bring attention to this issue, which may affect the choice of immunosuppressive regimen in the clinical setting.