Modulation of Cytochrome P450 Metabolism and Transport across Intestinal Epithelial Barrier by Ginger Biophenolics

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural ‘‘milieu’’ confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYPspecific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE’s inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an indepth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens

Non-standard errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Differential Impact of Monsoon and Large Amplitude Internal Waves on Coral Reef Development in the Andaman Sea

The Andaman Sea and other macrotidal semi-enclosed tropical seas feature large amplitude internal waves (LAIW). Although LAIW induce strong fluctuations i.e. of temperature, pH, and nutrients, their influence on reef development is so far unknown. A better-known source of disturbance is the monsoon affecting corals due to turbulent mixing and sedimentation. Because in the Andaman Sea both, LAIW and monsoon, act from the same westerly direction their relative contribution to reef development is difficult to discern. Here, we explore the framework development in a number of offshore island locations subjected to differential LAIW- and SW-monsoon impact to address this open question. Cumulative negative temperature anomalies – a proxy for LAIW impact – explained a higher percentage of the variability in coral reef framework height, than sedimentation rates which resulted mainly from the monsoon. Temperature anomalies and sediment grain size provided the best correlation with framework height suggesting that so far neglected subsurface processes (LAIW) play a significant role in shaping coral reefs

Processing of bulk copper-nickel sulfide concentrates by electrothermal smelting and matte leaching

The sulphide mineral of nickel is always associated with copper' and hence any treatment given to the mineral should aim at the recovery of both these metals. Although a number of processes involving direct leachng of sulphide concentrates using ferric chlorides, sulhuric acid2, nitric acic13,4, ammoniac etc, are being eveloped at various places, these processes involve either high pressures or pose problems of materials of construction. Pyrometallurgical processing of the copper-nickel sulphide concentrates results in high grade matte which can be further processed more conveniently and requires lesser quantity of material for subsequent treatments. In India, small tonnages of copper-nickel sulphide concen-trates are being generated as a byproduct in the recovery of Uranium at UCIL, Jaduguda. Because of the strategic importance of nickel, work was undertaken on the pyro-cum-hydrome-Ilurgical treatment of these concentrates for the recoery of copper and nickel values involving electrotheral smelting of the concentrates followed by HCl eaching of the matte

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Not AvailableMicroRNAs (miRNAs) are small non-coding RNAs which play an important role in regulating the genes involved in plant growth and development. Several studies showed that miRNAs are involved in plants response to different kinds of abiotic stresses also. In our previous study, temperature responsive miRNAs were predicted in O.sativa. 27 miRNAs were predicted to be novel in rice using homology search. In continuation to our previous study, expression of 14 novel miRNAs was done in shoot and root of 13 days old seedlings of five different rice cultivars using real time PCR. Expression these miRNAs was analyzed in control and high temperature stress environment. Out of 14 predicted novel miRNAs, two novel miRNAs- miR157a and miR165a showed expression in all five rice cultivars. Interestingly, miR165a showed a differential expression pattern among heat tolerant (N22, IR64 and Rasi) and susceptible (Vandana and Sampada) cultivars suggesting that it might have specific role in high temperature tolerance.Not Availabl

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Not AvailableMicroRNAs (miRNAs) are known to regulate expression of genes under stress. We report here the deep sequencing of small RNAs expressed during control, short and prolonged heat stress and recovery. Genome-wide identification of miRNAs in tolerant (Nagina 22) and susceptible (Vandana) rice cultivars was performed in 16 samples representing root and shoot of 13-day-old seedlings. The expression profile of miRNAs was analysed in 36 pairwise combinations to identify the genotype-, treatment- and tissue-dependent expression of miRNAs. Small-RNA sequencing of 16 libraries yielded ~271 million high-quality raw sequences; 162 miRNA families were identified. The highly expressed miRNAs in rice tissues were miR166, miR168, miR1425, miR529, mR162, miR1876, and miR1862. Expression of osa-miR1436, osa-miR5076, osa-miR5161, and osa-miR6253 was observed only in stressed tissue of both genotypes indicating their general role in heat stress response. Expression of osa-miR1439, osa-miR1848, osa-miR2096, osa-miR2106, osa-miR2875, osa-miR3981, osa-miR5079, osa-miR5151, osa-miR5484, osa-miR5792, and osa-miR5812 was observed only in Nagina 22 during high temperature, suggesting a specific role of these miRNAs in heat stress tolerance. This study provides details of the repertoire of miRNAs expressed in root and shoot of heat susceptible and tolerant rice genotypes under heat stress and recovery.Not Availabl

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Not AvailableThe cultivation of rice (Oryza sativa L.), a major food crop, requires ample water (30 % of the fresh water available worldwide), and its productivity is greatly affected by drought, the most significant environmental factor. Much research has focussed on identifying quantitative trait loci, stress-regulated genes and transcription factors that will contribute towards the development of climate-resilient/tolerant crop plants in general and rice in particular. The transcription factor DREB1A, identified from the model plant Arabidopsis thaliana, has been reported to enhance stress tolerance against drought stress. We developed transgenic rice plants with AtDREB1A in the background of indica rice cultivar Samba Mahsuri through Agrobacterium-mediated transformation. The AtDREB1A gene was stably inherited and expressed in T1 and T2 plants and in subsequent generations, as indicated by the results of PCR, Southern blot and RT-PCR analyses. Expression of AtDREB1A was induced by drought stress in transgenic rice lines, which were highly tolerant to severe water deficit stress in both the vegetative and reproductive stages without affecting their morphological or agronomic traits. The physiological studies revealed that the expression of AtDREB1A was associated with an increased accumulation of the osmotic substance proline, maintenance of chlorophyll, increased relative water content and decreased ion leakage under drought stress. Most of the homozygous lines were highly tolerant to drought stress and showed significantly a higher grain yield and spikelet fertility relative to the nontransgenic control plants under both stressed and unstressed conditions. The improvement in drought stress tolerance in combination with agronomic traits is very essential in high premium indica rice cultivars, such as Samba Mahsuri, so that farmers can benefit in times of seasonal droughts and water scarcity.Not Availabl