Thymoquinone protects renal tubular cells against tubular injury

In this work the effect of angiotensin II (AT II) on proximal tubular epithelial cells (pTECs) in vitro was studied. AT II was found to activate the nuclear factor kappaB (NF-kappaB) and its controlled genes, for example, interleukin 6 (IL-6) of pTECs in a time-dependent manner. Two points with maximum NF-kappaB activation were found, the first after 12 h and the second after 3.5 days. The first point may be due to activation of NF-kappaB in pTECs in response to AT II while the second may be due to activation of the advanced glycation end product (AGE)/receptor of the AGE (RAGE) system. Thymoquinone (TQ) was found to decrease NF-kappaB activation in a dose-dependant manner with maximum inhibitory effect at a concentration of 500 nM. Also, pre-incubation of pTECs with TQ leads to disappearance of the second peak of NF-kappaB. These data are consistent with results obtained from IL-6 enzyme-linked immunosorbent assay (ELISA) and transient transfection experiments. The results explain the therapeutic value of TQ which can be used to delay end stage renal diseases in diabetics.     

Self-protection of individual CD4+ T cells against R5 HIV-1 infection by the synthesis of anti-viral CCR5 ligands

It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8+ and CD4+ T cells can block the infection of activated CD4+ T cells by R5 and dual-tropic isolates of HIV-1. By contrast, because CD4+ T cells can be infected by HIV-1 and at least some subsets secrete anti-viral CCR5 ligands, it is possible that these ligands protect against HIV-1 via autocrine as well as paracrine pathways. Here we use a model primary CD4+ T cell response in vitro to show that individual CD4+ T cells that secrete anti-viral CCR5 ligands are 'self-protected' against infection with R5 but not X4 strains of HIV-1. This protection is selective for CD4+ T cells that secrete anti-viral CCR5 ligands in that activated CD4+ T cells in the same cultures remain infectable with R5 HIV-1. These data are most consistent with an autocrine pathway of protection in this system and indicate a previously unappreciated selective pressure on the emergence of viral variants and CD4+ T cell phenotypes during HIV-1 infection.     

A variational constitutive model for soft biological tissues

In this paper, a fully variational constitutive model of soft biological tissues is formulated in the finite strain regime. The model includes Ogden-type hyperelasticity, finite viscosity, deviatoric and volumetric plasticity, rate and microinertia effects. Variational updates are obtained via time discretization and pre-minimization of a suitable objective function with respect to internal variables. Genetic algorithms are used for model parameter identification due to their suitability for non-convex, high dimensional optimization problems. The material behavior predicted by the model is compared to available tests on swine and human brain tissue. The ability of the model to predict a wide range of experimentally observed behavior, including hysteresis, cyclic softening, rate effects, and plastic deformation is demonstrated.     

Docosahexaenoic acid sensitizes Ramos cells to Gamma-irradiation-induced apoptosis through involvement of PPAR-γ activation and NF-κB suppression

The aim of the present study was to characterize the effects of chronic nitric oxide synthase (NOS) inhibition on the alterations of regulatory myocardial proteins of intracellular signaling pathways (mitogen-activated protein kinase (MAPK) and Akt kinase cascades) and matrix metalloproteinases (MMP). Chronic NO deficiency (NOD) was induced by N^G-nitro-L-arginine methyl ester (L-NAME, 40mg/kg/day, 4 weeks). Protein levels and activation of protein kinases were determined using specific antibodies, activities of MMP were analyzed by zymography in gels containing gelatin as a substrate. The development of NOD was associated with decreased activation of endothelial NOS (eNOS) and down-regulation of protein level of inducible NOS (iNOS). Investigation of kinase pathways revealed that the activation of extracellular signal-regulated kinases (ERK) and the levels of upstream activators of ERK (aFGF, H-Ras) were decreased after L-NAME treatment. Western blot analysis revealed that chronic application of L-NAME also decreased the activation of Akt kinase as compared with control hearts. Study of MMPs showed that in L-NAME-treated rat hearts activities of tissue MMP-2 were decreased. It is concluded that development of NOD resulted in inhibition of ERK and Akt kinase pathways and these changes suggest the involvement of these cascades in responses of myocardium to NOD. The results also point to the possible relationship between ERK and Akt kinase pathways and activation of eNOS and/or MMP-2. Anna Špániková and Petra Šimončíková have contributed equally to the study.     

Brick by brick: metabolism and tumor cell growth

Tumor cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. Classical work in tumor cell metabolism focused on bioenergetics, particularly enhanced glycolysis and suppressed oxidative phosphorylation (the 'Warburg effect'). But the biosynthetic activities required to create daughter cells are equally important for tumor growth, and recent studies are now bringing these pathways into focus. In this review, we discuss how tumor cells achieve high rates of nucleotide and fatty acid synthesis, how oncogenes and tumor suppressors influence these activities, and how glutamine metabolism enables macromolecular synthesis in proliferating cells.     

Altitudinal Changes in Photosynthetic Pathways of Floristic Elements in Southern Sinai, Egypt

High altitude profoundly influenced plant diversity and distribution on mountains of southern Sinai (Egypt). Plants exhibiting the C₃-mode of photosynthesis were widely distributed along the altitudinal transect. Plants exhibiting the C₄-mode were restricted below an altitude of about 1400 m above sea level. The transition from C₃-dominated areas to C₄-dominated areas occurred between 1200 and 1400 m a.s.l. This revised version was published online in August 2006 with corrections to the Cover Date.     

Glycinebetaine-induced modulation of antioxidant enzymes activities and ion accumulation in two wheat cultivars differing in salt tolerance

Modulation of water relations, activities of antioxidant enzymes and ion accumulation was assessed in the plants of two wheat cultivars S-24 (salt tolerant) and MH-97 (moderately salt sensitive) subjected to saline conditions and glycinebetaine (GB) applied foliarly. Different levels of GB, i.e., 0 (unsprayed), 50 and 100 mM (in 0.10% Tween-20 solution) were applied to the wheat plants at the vegetative growth stage. Leaf water potential, leaf osmotic potential and turgor potential were decreased due to salt stress. Salt stress increased the Na⁺ and Cl⁻ accumulation coupled with a decrease in K⁺ and Ca²⁺ in the leaves and roots of both cultivars thereby decreasing tissue K⁺/Na⁺ and Ca²⁺/Na⁺ ratios. Furthermore, salt stress decreased the activities of superoxide dismutase (SOD), whereas it increased the activities of catalase (CAT) and peroxidase (POD) in both wheat cultivars. However, accumulation of GB in the leaves of both wheat cultivars was consistently increased with an increase in concentration of exogenous GB application under both non-saline and saline conditions. Accumulation of Na⁺ was decreased with an increase in K⁺ accumulation upon a consistent increase in GB accumulation under salt stress conditions thereby resulting in better K⁺/Na⁺ and Ca²⁺/Na⁺ ratios in the leaves and roots. High accumulation of GB and K⁺ mainly contributed to osmotic adjustment, which is one of the factors known to be responsible for improving growth and yield under salt stress. The activities of all antioxidant enzymes, SOD, CAT and POD were enhanced by GB application in cv. MH-97 under saline conditions, whereas all these except SOD were reduced in cv. S-24. It is likely that both applied GB and intrinsic SOD scavenged ROS in the tolerant cultivar thereby resulting into low activities of CAT and POD enzymes under salt stress. In conclusion, the adverse effects of salt stress on wheat can be alleviated by the exogenous application of 100 mM GB by modulating activities of antioxidant enzymes and changes in water relations and ion homeostasis. Furthermore, effectiveness of GB application on regulation of activities of antioxidant enzymes was found to be cultivar-specific.     

Agricultural diversification: the potential for underutilised crops in Africa's changing climates.

Two of the greatest challenges currently facing humanity are the potential consequences of climate change and the actual consequences of reduced agricultural diversity. This paper considers the consequences of both climate change and reduced agricultural diversity on global food security and nutrition. The inextricable link between climate change and crop diversity is examined, particularly in the context of crop production in Africa where most agricultural diversity exists and where climate change will have most impact. The Green Revolution, often seen as a model for increasing global agricultural productivity, is reconsidered in terms of its failure to make a significant impact in hostile tropical environments such as those of much of Africa. An alternative or, at least, a complementary strategy, is advocated where we might better harness the huge repository of indigenous plant species cultivated and conserved by local communities for many generations across variable climates. An example is given of multidisciplinary research on bambara groundnut (Vigna subterranea), an ancient grain legume grown, cooked, processed and traded mainly by subsistence women farmers in sub-Saharan Africa. The experience gained on bambara groundnut is considered as a basis for similar efforts on many other potentially useful underutilised food crops in the climates of the future.