Arabidopsis plants overexpressing additional copies of heat shock protein Hsp101 showed high heat tolerance and endo-gene silencing.

Hsp101 chaperone is vital for survival of plants under heat stress. We generated transgenic Arabidopsis thaliana (Arabidopsis) lines with extra copies of Hsp101 gene using diverse approaches. Arabidopsis plants transformed with rice Hsp101 cDNA driven by Arabidopsis Hsp101 promoter (IN lines) showed high heat tolerance while the plants transformed with rice Hsp101 cDNA driven by CaMV35S promoter (C lines) were like wild type plants in heat stress response. Transformation of Col-0 plants with 4633 bp Hsp101 genomic fragment (GF lines) from A. thaliana containing both its coding and the regulatory sequence resulted in mostly over-expressor (OX) lines and a few under-expressor (UX) lines of Hsp101. OX lines showed enhanced heat tolerance while the UX lines were overly heat sensitive. In UX lines, silencing of not only Hsp101 endo-gene was noted but also transcript of choline kinase (CK2) was silenced. Previous work established that in Arabidopsis, CK2 and Hsp101 are convergent gene pairs sharing a bidirectional promoter. The elevated AtHsp101 protein amount in most GF and IN lines was accompanied by lowered CK2 transcript levels under HS. We observed increased methylation of the promoter and gene sequence region in UX lines; however, methylation was lacking in OX lines.

Fruit peel bioactives, valorisation into nanoparticles and potential applications: A review.

Nanotechnology is a rapidly growing field with profound applications in different domains, particularly in food science and technology. Nanoparticles (NPs) synthesis, an integral part of nanotechnology-based applications, is broadly classified into chemical, physical and biosynthesis methods. Chemically sensitive and energy-intensive procedures employed for NPs synthesis are some of the limits of traditional chemical approaches. Recent research has focused on developing easy, nontoxic, cost-effective, and environment-friendly NPs synthesis during the last decade. Biosynthesis approaches have been developed to achieve this goal as it is a viable alternative to existing chemical techniques for the synthesis of metallic nanomaterials. Fruit peels contain abundant bioactive compounds including phenols, flavonoids, tannins, triterpenoids, steroids, glycosides, carotenoids, anthocyanins, ellagitannins, vitamin C, and essential oils with substantial health benefits, anti-bacterial and antioxidant properties, generally discarded as byproduct or waste by the fruit processing industry. NPs synthesized using bioactive compounds from fruit peel has futuristic applications for an unrealized market potential for nutraceutical and pharmaceutical delivery. Numerous studies have been conducted for the biosynthesis of metallic NPs such as silver (AgNPs), gold (AuNPs), zinc oxide, iron, copper, palladium and titanium using fruit peel extract, and their synthesis mechanism have been reported in the present review. Additionally, NPs synthesis methods and applications of fruit peel NPs have been discussed.

Tillage, green manure and residue retention improves aggregate-associated phosphorus fractions under rice-wheat cropping.

The sustainability of the rice-wheat system is threatened due to the deterioration of soil health and emergence of new challenges of climate change caused by low nutrient use efficiency and large scale burning of crop residues. The conservation agriculture based on tillage intensity, crop residue retention and raising green manuring (GM) crops during the intervening period between wheat harvest and rice establishment offers opportunities for restoration of phosphorus (P) dynamics and stimulate phosphatase activities within the macro-and micro-aggregates. Phosphorus and phosphatase activities in the soil aggregates affected by different residue management practices remain poorly understood. Thus, soil samples were obtained after a five-year field experiment to identify the effect of tillage, green manure and residue management on aggregate-associated phosphorus fractions. Four main plot treatments in rice included combination of wheat straw and GM were conventional till puddled transplanted rice (PTR) with no wheat straw (PTRW0), PTR with 25% wheat stubbles retained (PTRW25), PTR without wheat straw and GM (PTRW0 + GM), and PTR with wheat stubbles and GM (PTRW25 + GM). Three sub-plots treatments in the successive wheat crop were conventional tillage (CT) with rice straw removed (CTWR0), zero tillage (ZT) with rice straw removed (ZTWR0) and ZT with rice straw retained as surface mulch (ZTWR100). Results of the present study revealed significantly higher phosphorus fractions (HCl-P, NaHCO3-Pi and NaOH-Po) in treatment PTRW25 + GM and ZTWR100 compared with PTRW0/CTWR0 within both macro- and micro-aggregates. The total phosphorus (P), available P, alkaline phosphatase and phytin-P were significantly higher under ZTWR100 than CTWR0. The principal component analysis identified NaOH-Po, NaHCO3-Pi and HCl-P as the dominant and reliable indicators for evaluating P transformation within aggregates under conservation agriculture-based practices.

Iron oxide nanoparticles and selenium supplementation improve growth and photosynthesis by modulating antioxidant system and gene expression of chlorophyll synthase (CHLG) and protochlorophyllide oxidoreductase (POR) in arsenic-stressed Cucumis melo.

Current research reveals the positive role of iron oxide nanoparticles (IONPs) and selenium (Se) in extenuation of arsenic (As) induced toxicity in Cucumis melo. C. melo plants grown in As spiked soil (20 mg kg-1 As) showed reduced growth, chlorophyll (Chl) content, photosynthetic rate, stomatal conductivity and transpiration. On the other hand, the alone applications of IONPs or Se improved growth and physiochemical parameters of C. melo plants. Additionally, exogenous application IONPs and Se synergistically improved the activity of antioxidative enzymes and glyoxalase system in C. melo plants. In addition, the collective treatment of IONPs and Se reduced As uptake, enhanced rate of photosynthesis and increased gas exchange attributes of C. melo plants under As stress. Interactive effect of IONPs and Se regulated reduced glutathione (GSH), oxidized glutathione (GSSG) and ascorbate (AsA) content in C. melo plants exposed to As-contaminated Soil. IONPs and Se treatment also regulated expression of respiratory burst oxidase homologue D (RBOHD) gene, chlorophyll synthase (CHLG) and protochlorophyllide oxidoreductase (POR). Therefore, the combined treatment of IONPs and Se may enhance the growth of crop plants by alleviating As stress.

Integrated use of phosphorus, farmyard manure and biofertilizer improves the yield and phosphorus uptake of black gram in silt loam soil.

An experiment on the use of farmyard manure and biofertilizer along with application of chemical phosphorus was conducted to assess the impact of differential doses of phosphorus, farmyard manure and consortium biofertilizer application on the development, yield and phosphorus uptake during the year 2018 and 2019. The impact of different treatments was recorded on the plant height, dry matter partition, yield and yield attributes, phosphorus uptake and soil phosphorus availability using standard methods. The data revealed significant improvement in yield, yield attributes, phosphorus uptake and soil phosphorus availability. The integration of farmyard manure and biofertilizer with 60 kg ha-1 SSP (single superphosphate) has improved the black gram yield by 7.4% and 3.28% respectively over the use of 60 SSP alone. The phosphorus uptake in black gram with application of Farm yard manure and biofertilizer along with 60 kg ha-1 SSP has improved the uptake by 7.18% and 2.51% respectively over the use of 60 kg ha-1 SSP alone. The results highlight the need of integrated application of farm yard manure, biofertilizer for sustainable production of black gram in the region.

Genetic and molecular mechanisms underlying root architecture and function under heat stress-A hidden story.

Heat stress events are resulting in a significant negative impact on global food production. The dynamics of cellular, molecular and physiological homoeostasis in aboveground parts under heat stress are extensively deciphered. However, root responses to higher soil/air temperature or stress signalling from shoot to root are limited. Therefore, this review presents a holistic view of root physio-morphological and molecular responses to adapt under hotter environments. Heat stress reprogrammes root cellular machinery, including crosstalk between genes, phytohormones, reactive oxygen species (ROS) and antioxidants. Spatio-temporal regulation and long-distance transport of phytohormones, such as auxin, cytokinin and abscisic acid (ABA) determine the root growth and development under heat stress. ABA cardinally integrates a signalling pathway involving heat shock factors, heat shock proteins and ROS to govern heat stress responses. Additionally, epigenetic modifications by transposable elements, DNA methylation and acetylation also regulate root growth under heat stress. Exogenous application of chemical compounds or biological agents such as ascorbic acid, metal ion chelators, fungi and bacteria can alleviate heat stress-induced reduction in root biomass. Future research should focus on the systemic effect of heat stress from shoot to root with more detailed investigations to decipher the molecular cues underlying the roots architecture and function.

Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (CA) is commonly used herbal medicine for treatment of epilepsy. CA has CYP2C9, CYP2D6 and CYP3A4 enzymes inhibition property and used as an adjuvant therapy with conventional antiepileptic drugs (AEDs). That may be responsible for herb-drug interaction. AIM OF THE STUDY: The present study was planned to evaluate interactions profile of hydroalcoholic extract Centella asiatica (HECA) with antiepileptic drugs in experimental models of epilepsy in rats. MATERIALS AND METHODS: Wistar rats (175-200 g) were used. In the pharmacodynamic interaction study, seizures were induced using pentylenetetrazole (PTZ) (60 mg/kg, i.p.) and maximal electroshock seizure (MES) (70 mA for 0.2 s). The therapeutic and sub-therapeutic doses of valproate (VPA) and phenytoin (PHT) were co-administrated with HECA in PTZ and MES model of seizures respectively. Behavioural parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were also assessed. In the pharmacokinetic interaction study, the serum levels of the VPA and PHT were estimated at different time intervals by HPLC and pharmacokinetic parameters were analyzed by WinNonlin software. RESULTS: The VPA and PHT produced complete protection against seizures in their therapeutic doses but not with sub-therapeutic doses. However, co-administration of HECA with a sub-therapeutic dose of VPA and PHT enhanced the protection of seizures and significantly (p < 0.001) attenuated the seizure induced oxidative stress and cognitive impairment. It also significantly increased (p < 0.001) serum levels of VPA and PHT. The alterations in pharmacokinetic parameters (maximum serum concentration, area under the curve, clearance) of AEDs were also found with co-administration of HECA. CONCLUSION: The results suggested that co-administration of HECA could improve the therapeutic efficacy of VPA and PHT. But, alteration in pharmacokinetic parameters revel that needs critical medical supervision to avoid any toxic reactions.

Bacosides enrichment does not improve the anti-amnesic effect of Bacopa monnieri: behavioural and biochemical evidences.

Bacopa monnieri (L.) Wettst. (BM) has been traditionally used in Ayurveda for improving memory and cognitive deficits which is also evidenced through experimental and clinical studies. The neuropharmacological properties of BM are attributed to "bacosides", a complex mixture of saponin compounds. BM extracts enriched with bacosides offers commercial advantage due to perceived higher efficacy. However, there is no scientific data to support the same. In the present study, methanolic extract of BM (BME) was compared with bacosides enriched (BME-EF) vis a vis bacosides free fraction (BME-FF). Potential antioxidant and cholinesterase inhibitory activity has been evaluated using in vitro and in vivo methods. BME showed not only the highest anti-amnesic efficacy but also antioxidant and cholinesterase inhibitory activity, followed by either BME-FF or BME-EF. Interestingly, no significant differences were found in between the groups. These findings dispel the notion that bacosides enrichment enhances anti-amnesic efficacy and also suggests the contribution of other components.

Comparative temporal metabolomics studies to investigate interspecies variation in three Ocimum species.

Ocimum is one of the most revered medicinally useful plants which have various species. Each of the species is distinct in terms of metabolite composition as well as the medicinal property. Some basil types are used more often as an aromatic and flavoring ingredient. It would be informative to know relatedness among the species which though belong to the same genera while exclusively different in terms of metabolic composition and the operating pathways. In the present investigation the similar effort has been made in order to differentiate three commonly occurring Ocimum species having the high medicinal value, these are Ocimum sanctum, O. gratissimum and O. kilimandscharicum. The parameters for the comparative analysis of these three Ocimum species comprised of temporal changes in number leaf trichomes, essential oil composition, phenylpropanoid pathway genes expression and the activity of important enzymes. O. gratissimum was found to be richest in phenylpropanoid accumulation as well as their gene expression when compared to O. sanctum while O. kilimandscharicum was found to be accumulating terpenoid. In order to get an overview of this qualitative and quantitative regulation of terpenes and phenylpropenes, the expression pattern of some important transcription factors involved in secondary metabolism were also studied.

Ocimum metabolomics in response to abiotic stresses: Cold, flood, drought and salinity.

Ocimum tenuiflorum is a widely used medicinal plant since ancient times and still continues to be irreplaceable due to its properties. The plant has been explored chemically and pharmacologically, however, the molecular studies have been started lately. In an attempt to get a comprehensive overview of the abiotic stress response in O. tenuiflorum, de novo transcriptome sequencing of plant leaves under the cold, drought, flood and salinity stresses was carried out. A comparative differential gene expression (DGE) study was carried out between the common transcripts in each stress with respect to the control. KEGG pathway analysis and gene ontology (GO) enrichment studies exhibited several modifications in metabolic pathways as the result of four abiotic stresses. Besides this, a comparative metabolite profiling of stress and control samples was performed. Among the cold, drought, flood and salinity stresses, the plant was most susceptible to the cold stress. Severe treatments of all these abiotic stresses also decreased eugenol which is the main secondary metabolite present in the O. tenuiflorum plant. This investigation presents a comprehensive analysis of the abiotic stress effects in O. tenuiflorum. Current study provides an insight to the status of pathway genes' expression that help synthesizing economically valuable phenylpropanoids and terpenoids related to the adaptation of the plant. This study identified several putative abiotic stress tolerant genes which can be utilized to either breed stress tolerant O. tenuiflorum through pyramiding or generating transgenic plants.

Comparison of three different extracts of Centella asiatica for anti-amnesic, antioxidant and anticholinergic activities: in vitro and in vivo study.

Centella asiatica (CA) has been used by Ayurvedic medical practitioners in India for almost 3000 years. The neuropharmacological properties of CA and its constituents have been studied extensively. Anti-oxidant, free radical scavenging and cholinergic modulatory activities are the reported mechanisms of action for its efficacy in memory disorders. Its medicinal values are mainly attributed to the presence of several triterpenes, namely asiatic acid, madecassic acid, asiaticoside, and madecassoside. The present study was aimed to investigate the role of these triterpenes content in CA extract on the antioxidant, cholinesterase modulation and anti-amnesic properties. The fractions of CA extract enriched for (CAE-EF) and depleted/freed of (CAE-FF) triterpenes contents were compared with methanolic extract (CAE). Both in vitro and in vivo methods for evaluation of antioxidant and anticholinergic activities were used. In vitro, free radical scavenging assays (ABTS, DPPH, NO, NORAC, and ORAC) and cholinesterase (AChE and BuChE) inhibition assays were used. For evaluation of anti-amnesic effect, scopolamine induced amnesia in rats, as the acute model of memory loss was used. Following behavioural assessments (MWM, PA, EPM), biomarkers of oxidative stress (reduced GSH, MDA and SOD activity) and cholinesterase (AChE and BuChE) status were also estimated in cerebral cortex and hippocampus of rat brain. The methanolic extract (CAE) was found to perform best among all three fractions for in vitro free radical scavenging, cholinesterase inhibition, improvement of scopolamine-induced amnesia and also in vivo antioxidant effect and cholinesterase inhibitory activities. Interestingly triterpenes free fraction (CAE-FF) showed better antioxidant activity than triterpenes enriched fraction (CAE-EF) along with comparable anti-amnesic effect. This indicates that triterpenes are not solely responsible for antioxidant activity, cholinesterase inhibitory and anti-amnesic effect of CA.

Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Teminalia chebula (TC) has been traditionally used in the Ayurvedic system of medicine primarily for gastrointestinal disorders. Its fruit extract has also been used to treat epilepsy and other CNS disorders. AIM OF THE STUDY: To evaluate the effect of hydroalcoholic fruit extract of Terminalia chebula (HETC) on experimental models of seizures, seizure-induced cognitive impairment and oxidative stress in rats. MATERIALS AND METHODS: In vitro antioxidant activity of HETC was evaluated by using ABTS, NO and DPPH radical scavenging assay. For in-vivo study, seizures were induced in Wistar rats (200-225g) by pentylenetetrazole (PTZ) and maximal-electroshock. (MES). The anticonvulsant effect of the HETC (250, 500, and 1000mg/kg, orally) was evaluated in seizure models. The therapeutic and sub-therapeutic dose of valproate and phenytoin were also assayed. The potential effect of co-administration of HETC (500mg/kg) with sub-therapeutic dose of valproate and phenytoin were also evaluated in PTZ and MES seizures model respectively. Effect on cognition was assessed using elevated plus maze (EPM) and passive avoidance test (PA). The in- vivo oxidative stress parameters (malondialdehyde and glutathione) were assessed in the cerebral cortex and hippocampus part of rat brain. RESULTS: The IC50 value of HETC in in vitro antioxidant assays i.e. ABTS, DPPH and NO radical scavenging assay was found to be 2.27µg/ml, 6.04µg/ml and 4.37µg/ml respectively. In experimental study, PTZ and MES treated groups exhibited 100% seizures with increased oxidative stress (p < 0.001) and cognitive deficits (p < 0.01) as compared to control group. HETC at highest dose (1000mg/kg) showed 83.33% (5/6) protection in MES induced seizures while 66.66% (4/6) protection in PTZ induced seizures. However, HETC (1000mg/kg) and co-administration of sub-therapeutic dose of HETC with valproate and phenytoin showed complete protection. In addition, it also attenuated the seizure induced oxidative stress and cognitive impairment as indicated by significant (p < 0.01) improvement in the transfer latencies in EPM and PA as compared to PTZ and MES treated group. CONCLUSIONS: The findings suggest that HETC exhibited significant anticonvulsant activity and also potentiated the subtherapeutic dose of phenytoin and valproate indicate its usefulness as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.

Pharmacokinetic and pharmacodynamic interaction of hydroalcoholic extract of Ocimum sanctum with valproate.

For effective control of seizures, antiepileptic drugs (AEDs) are administered at higher dose which is associated with several adverse effects. This study envisaged antiepileptic and neuroprotective potential of Tulsi, a commonly used herb for its immunomodulatory property. The optimal dose of Ocimum sanctum hydroalcoholic extract (OSHE) was determined using maximal electroshock seizure (MES)- and pentylenetetrazol (PTZ)-induced seizure models in Wistar rats (200-250g) after administering OSHE (200-1000mg/kg) orally for 14days. For interaction study, OSHE optimal dose in combination with maximum and submaximal therapeutic doses of valproate was administered for 14days. Serum levels of valproate were estimated using HPLC for pharmacokinetic study. For pharmacodynamic interaction, antiepileptic effect on above seizure models, neurobehavioral effect using Morris water maze, passive avoidance and elevated plus maze tests, and antioxidant capacity were assessed. Ocimum sanctum hydroalcoholic extract 1000mg/kg was found to be optimal providing 50% protection against both MES- and PTZ-induced seizures. Combination of OSHE with valproate did not alter antiepileptic efficacy of valproate significantly. However, the combination showed better memory retention potential in neurobehavioral tests and protection against oxidative stress compared with valproate-alone-treated groups. Pharmacokinetic parameters did not reveal any significant change in combination group compared with valproate alone. Ocimum, although having per se antiepileptic action, did not affect antiepileptic action of valproate in combination. However, combination treatment has an edge over valproate alone-better neurobehavioral function and reduced oxidative stress-predicting adjuvant potential of Ocimum in epilepsy treatment.

Molecular events leading to death of Leishmania donovani under spermidine starvation after hypericin treatment.

We have previously reported that the hypericin treatment caused spermidine starvation and death of Leishmania parasite. Here, we report different molecular events under spermidine starvation and potential role of spermidine in processes other than redox homeostasis of the parasite. We have analyzed changes in expression of several genes by using quantitative gene expression analysis. Further, these changes at molecular level were also confirmed by using biochemical and cellular studies. Altered expression of several genes involved in redox metabolism, hypusine modification of eIF5A, DNA repair pathway and autophagy was observed. There was decrease in Sir2RP expression after hypericin treatment and this decrease has been found to be associated with induced ROS due to hypericin treatment as it has been rescued by either trypanothione or spermidine supplementation. Translation initiation in the parasite was decreased upon spermidine starvation. We also observed increased AMPK expression upon hypericin treatment. The increase in intracellular ATP and NAD+ levels as well as decrease in Sir2RP expression of the parasite are cytoprotective mechanism towards generated ROS due to hypericin treatment possibly by inducing autophagy as indicated by increase in autophagy related gene expression and acridine orange staining. However, the autophagy needs to be established using more rigorous methodologies.

CO variability and its association with household cooking fuels consumption over the Indo-Gangetic Plains.

This study examines the spatio-temporal trends obtained from decade long (Jan 2003-Dec 2014) satellite observational data of Atmospheric Infrared Sounder (AIRS) and Measurements of Pollution in the Troposphere (MOPITT) on carbon monoxide (CO) concentration over the Indo-Gangetic Plains (IGP) region. The time sequence plots of columnar CO levels over the western, central and eastern IGP regions reveal marked seasonal behaviour, with lowest CO levels occurring during the monsoon months and the highest CO levels occurring during the pre-monsoon period. A negative correlation between CO levels and rainfall is observed. CO vertical profiles show relatively high values in the upper troposphere at ∼200 hPa level during the monsoon months, thus suggesting the role of convective transport and advection in addition to washout behind the decreased CO levels during this period. MOPITT and AIRS observations show a decreasing trend of 9.6 × 1015 and 1.5 × 1016 molecules cm-2 yr-1, respectively, in columnar CO levels over the IGP region. The results show the existence of a spatial gradient in CO from the eastern (higher levels) to western IGP region (lower levels). Data from the Census of India on the number of households using various cooking fuels in the IGP region shows the prevalence of biomass-fuel (i.e. firewood, crop residue, cowdung etc.) use over the eastern and central IGP regions and that of liquefied petroleum gas over the western IGP region. CO emission estimates from cooking activity over the three IGP regions are found to be in the order east > central > west, which support the existence of the spatial gradient in CO from eastern to the western IGP region. Our results support the intervention of present Indian government on limiting the use of biomass-fuels in domestic cooking to achieve the benefits in terms of the better air quality, household health and regional/global climate change mitigation.

Towards biological plausibility of electronic noses: A spiking neural network based approach for tea odour classification.

The paper presents a novel encoding scheme for neuronal code generation for odour recognition using an electronic nose (EN). This scheme is based on channel encoding using multiple Gaussian receptive fields superimposed over the temporal EN responses. The encoded data is further applied to a spiking neural network (SNN) for pattern classification. Two forms of SNN, a back-propagation based SpikeProp and a dynamic evolving SNN are used to learn the encoded responses. The effects of information encoding on the performance of SNNs have been investigated. Statistical tests have been performed to determine the contribution of the SNN and the encoding scheme to overall odour discrimination. The approach has been implemented in odour classification of orthodox black tea (Kangra-Himachal Pradesh Region) thereby demonstrating a biomimetic approach for EN data analysis.

De-novo RNA sequencing and metabolite profiling to identify genes involved in anthocyanin biosynthesis in Korean black raspberry (Rubus coreanus Miquel).

The Korean black raspberry (Rubus coreanus Miquel, KB) on ripening is usually consumed as fresh fruit, whereas the unripe KB has been widely used as a source of traditional herbal medicine. Such a stage specific utilization of KB has been assumed due to the changing metabolite profile during fruit ripening process, but so far molecular and biochemical changes during its fruit maturation are poorly understood. To analyze biochemical changes during fruit ripening process at molecular level, firstly, we have sequenced, assembled, and annotated the transcriptome of KB fruits. Over 4.86 Gb of normalized cDNA prepared from fruits was sequenced using Illumina HiSeq™ 2000, and assembled into 43,723 unigenes. Secondly, we have reported that alterations in anthocyanins and proanthocyanidins are the major factors facilitating variations in these stages of fruits. In addition, up-regulation of F3'H1, DFR4 and LDOX1 resulted in the accumulation of cyanidin derivatives during the ripening process of KB, indicating the positive relationship between the expression of anthocyanin biosynthetic genes and the anthocyanin accumulation. Furthermore, the ability of RcMCHI2 (R. coreanus Miquel chalcone flavanone isomerase 2) gene to complement Arabidopsis transparent testa 5 mutant supported the feasibility of our transcriptome library to provide the gene resources for improving plant nutrition and pigmentation. Taken together, these datasets obtained from transcriptome library and metabolic profiling would be helpful to define the gene-metabolite relationships in this non-model plant.

The structure of the BfrB-Bfd complex reveals protein-protein interactions enabling iron release from bacterioferritin.

Ferritin-like molecules are unique to cellular iron homeostasis because they can store iron at concentrations much higher than those dictated by the solubility of Fe(3+). Very little is known about the protein interactions that deliver iron for storage or promote the mobilization of stored iron from ferritin-like molecules. Here, we report the X-ray crystal structure of Pseudomonas aeruginosa bacterioferritin (Pa-BfrB) in complex with bacterioferritin-associated ferredoxin (Pa-Bfd) at 2.0 Å resolution. As the first example of a ferritin-like molecule in complex with a cognate partner, the structure provides unprecedented insight into the complementary interface that enables the [2Fe-2S] cluster of Pa-Bfd to promote heme-mediated electron transfer through the BfrB protein dielectric (~18 Å), a process that is necessary to reduce the core ferric mineral and facilitate mobilization of Fe(2+). The Pa-BfrB-Bfd complex also revealed the first structure of a Bfd, thus providing a first view to what appears to be a versatile metal binding domain ubiquitous to the large Fer2_BFD family of proteins and enzymes with diverse functions. Residues at the Pa-BfrB-Bfd interface are highly conserved in Bfr and Bfd sequences from a number of pathogenic bacteria, suggesting that the specific recognition between Pa-BfrB and Pa-Bfd is of widespread significance to the understanding of bacterial iron homeostasis.

Experimental Assessment of Moringa oleifera Leaf and Fruit for Its Antistress, Antioxidant, and Scavenging Potential Using In Vitro and In Vivo Assays.

We have investigated effect of Moringa oleifera leaf and fruit extracts on markers of oxidative stress, its toxicity evaluation, and correlation with antioxidant properties using in vitro and in vitro assays. The aqueous extract of leaf was able to increase the GSH and reduce MDA level in a concentration-dependent manner. The ethanolic extract of fruit showed highest phenolic content, strong reducing power and free radical scavenging capacity. The antioxidant capacity of ethanolic extract of both fruit and leaf was higher in the in vitro assay compared to aqueous extract which showed higher potential in vivo. Safety evaluation studies showed no toxicity of the extracts up to a dose of 100 mg/kg body weight. Our results support the potent antioxidant activity of aqueous and ethanolic extract of Moringa oleifera which adds one more positive attribute to its known pharmacological importance.

Cost-effectiveness of raltegravir in HIV/AIDS.

Raltegravir is a first-in-class HIV-1 integrase inhibitor with established antiviral efficacy in treatment-naive and treatment-experienced patients with multidrug-resistant HIV-1 infection. In this article, we summarize pharmacoeconomic evaluations of raltegravir-based treatment regimens, compared with alternative therapies, in the treatment of patients with HIV infection and/or AIDS. Cost-effectiveness evaluations of raltegravir in treatment-experienced patients conducted using a continuous-time, state-transition Markov cohort model suggest that raltegravir, combined with optimized background therapy, falls within the range that would generally be considered cost effective compared with optimized therapy alone in Spanish, Swiss and UK health systems. In treatment-naive populations, raltegravir was evaluated using a three-stage continuous-time state-transition cohort model. Raltegravir-based initiation treatment strategies (first-line raltegravir) were compared with protease inhibitor and non-nucleoside reverse-transcriptase inhibitor initiation strategies, in which raltegravir was retained for salvage therapy. First-line raltegravir was cost-effective versus retaining raltegravir for salvage therapy in several European populations. A separate economic model was used to evaluate first-line raltegravir against two alternative initiation regimens representing standard clinical practice in Australia; raltegravir proved to be cost effective in both scenarios. In all studies examined, results were sensitive to factors including treatment duration, mortality rate, analytic time horizon, health utility weights, cost of raltegravir and optimized therapy, incidence of opportunistic infection and discount rates. Nonetheless, raltegravir remained cost effective under most scenarios.