WRKY transcription factors and plant defense responses: latest discoveries and future prospects.

KEY MESSAGE: WRKY transcription factors are among the largest families of transcriptional regulators. In this review, their pivotal role in modulating various signal transduction pathways during biotic and abiotic stresses is discussed. Transcription factors (TFs) are important constituents of plant signaling pathways that define plant responses against biotic and abiotic stimuli besides playing a role in response to internal signals which coordinate different interacting partners during developmental processes. WRKY TFs, deriving their nomenclature from their signature DNA-binding sequence, represent one of the largest families of transcriptional regulators found exclusively in plants. By modulating different signal transduction pathways, these TFs contribute to various plant processes including nutrient deprivation, embryogenesis, seed and trichome development, senescence as well as other developmental and hormone-regulated processes. A growing body of research suggests transcriptional regulation of WRKY TFs in adapting plant to a variety of stressed environments. WRKY TFs can regulate diverse biological functions from receptors for pathogen triggered immunity, modulator of chromatin for specific interaction and signal transfer through a complicated network of genes. Latest discoveries illustrate the interaction of WRKY proteins with other TFs to form an integral part of signaling webs that regulate several seemingly disparate processes and defense-related genes, thus establishing their significant contributions to plant immune response. The present review starts with a brief description on the structural characteristics of WRKY TFs followed by the sections that present recent evidence on their roles in diverse biological processes in plants. We provide a comprehensive overview on regulatory crosstalks involving WRKY TFs during multiple stress responses in plants and future prospects of WRKY TFs as promising molecular diagnostics for enhancing crop improvement.

The Oral Iron Chelator, Deferasirox, Reverses the Age-Dependent Alterations in Iron and Amyloid-ß Homeostasis in Rat Brain: Implications in the Therapy of Alzheimer's Disease.

The altered metabolism of iron impacts the brain function in multiple deleterious ways during normal aging as well as in Alzheimer's disease. We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid-ß (Aß) peptide homeostasis in the aging brain, such as an increased production of the amyloid-ß protein precursor, a decreased level of neprilysin, and increased accumulation of Aß42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented. More interestingly, the chelator treatment also considerably reverses the altered Aß peptide metabolism in the aging brain implying a significant role of iron in the latter phenomenon. Further, other results indicate that iron accumulation results in oxidative stress and the activation of NF-κB in the aged rat brain, which are also reversed by the deferasirox treatment. The analysis of the results together suggests that iron accumulation and oxidative stress interact at multiple levels that include transcriptional and post-transcriptional mechanisms to bring about changes in the expression levels of TfR1 and ferritin and also alterations in Aß peptide metabolism in the aging rat brain. The efficacy of deferasirox in preventing age-related changes in iron and Aß peptide metabolism in the aging brain, as shown here, has obvious therapeutic implications for Alzheimer's disease.

Vertical and horizontal proportions of the face and their correlation to phi among Indians in Moradabad population: A survey.

PURPOSE: The purpose was to examine the existence of divine proportions among the Indian faces in Moradabad population. MATERIALS AND METHODS: Totally, 100 patients (50 males; 50 females) aged 25-45 years were selected for the study. All facial photographs were analyzed based on the method of Ricketts assessing the divine proportions in vertical and transverse facial planes. Six horizontal and seven vertical ratios were determined, which were then compared with the phi ratio. RESULTS: The horizontal ratio results showed that three male and female ratios were not significantly different from each other (P > 0.05), and interchilion/nose width ratio was highly significant (P < 0.001). The horizontal mean ratios for females as well as males were highly significant from the phi ratio (P < 0.001) except for interchilion/interdacryon ratio, which was significant (P < 0.05) for females and not significant (P > 0.05) for males. The vertical ratio results showed that there was a highly significant difference (P < 0.001) for forehead height/stomion-soft menton ratio and no significant difference for two ratios between the mean ratios of males and females. All the vertical mean ratios for both the groups were highly significant (P < 0.001), except for the intereye-soft menton/intereye-stomion ratio, which was significant (P < 0.05) for female group and not significant (P > 0.05) for the male group. CONCLUSION: Although, the golden proportion is a prominent and recurring theme in esthetics, it should not be embraced as the only method by which human beauty is measured to the exclusion of others factors.

α-Synuclein-induced mitochondrial dysfunction in isolated preparation and intact cells: implications in the pathogenesis of Parkinson's disease.

This study has shown that purified recombinant human α-synuclein (20 µM) causes membrane depolarization and loss of phosphorylation capacity of isolated purified rat brain mitochondria by activating permeability transition pore complex. In intact SHSY5Y (human neuroblastoma cell line) cells, lactacystin (5 µM), a proteasomal inhibitor, causes an accumulation of α-synuclein with concomitant mitochondrial dysfunction and cell death. The effects of lactacystin on intact SHSY5Y cells are, however, prevented by knocking down α-synuclein expression by specific siRNA. Furthermore, in wild-type (non-transfected) SHSY5Y cells, the effects of lactacystin on mitochondrial function and cell viability are also prevented by cyclosporin A (1 µM) which blocks the activity of the mitochondrial permeability transition pore. Likewise, in wild-type SHSY5Y cells, typical mitochondrial poison like antimycin A (50 nM) produces loss of cell viability comparable to that of lactacystin (5 µM). These data, in combination with those from isolated brain mitochondria, strongly suggest that intracellularly accumulated α-synuclein can interact with mitochondria in intact SHSY5Y cells causing dysfunction of the organelle which drives the cell death under our experimental conditions. The results have clear implications in the pathogenesis of sporadic Parkinson's disease. α-Synuclein is shown to cause mitochondrial impairment through interaction with permeability transition pore complex in isolated preparations. Intracellular accumulation of α-synuclein in SHSY5Y cells following proteasomal inhibition leads to mitochondrial impairment and cell death which could be prevented by knocking down α-synuclein gene. The results link mitochondrial dysfunction and α-synuclein accumulation, two key pathogenic mechanisms of Parkinson's disease, in a common damage pathway.

Multiple mechanisms of iron-induced amyloid beta-peptide accumulation in SHSY5Y cells: protective action of negletein.

The increased accumulation of iron in the brain in Alzheimer's disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased ß-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in ß-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of negletein, which should be explored in suitable animal models of AD.

In sight, in mind: retailer compliance with legislation on limiting retail tobacco displays.

We investigated retailer compliance with point-of-sale display legislation, using a New Zealand region as a case study. An observational survey was conducted of nonspecialist tobacco retailers in the lower North Island of New Zealand during 2006. Compliance was assessed in relation to store type (dairies, convenience stores, supermarkets, and service stations) and by characteristics of the population of the census area unit in which the store was situated. These characteristics include the level of socioeconomic deprivation and proportions of Maori (indigenous New Zealanders), Pacific Islanders, and children aged less than 19 years. Out of the 288 stores surveyed, 185 (64%) had at least one breach of the point-of-sale regulations. The most common breaches were a failure to display a "Smoking Kills" sign, visibility of tobacco from outside the premises, and displaying tobacco less than 1 m from children's products. Compliance was significantly worse in dairies (small local general stores) and convenience stores. Stores situated in areas in the top quartile for the proportion of children were much more likely to have high levels of noncompliance (> or =3 breaches) and to display tobacco products close to children's products. This study is one of very few to systematically investigate retailer compliance with point-of-sale display regulations for tobacco products. The results suggest that the implementation of legislation to partly limit retail displays of tobacco products can be difficult. A ban on retail displays of tobacco products is likely to be a more effective and enforceable policy.