Seasonal Changes in the Antioxidative Defence System of a Liverwort Dumortiera hirsuta

Journal of Plant Growth Regulation - Liverworts are influenced by several ecological factors, such as photoperiod, temperature, precipitation, and nutrient availability. These factors vary in...     

A Randomized,Placebo-Controlled Study of SRT2104, a SIRT1 Activator,in Patients with Moderate to Severe Psoriasis

Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. We randomized 40 patients with moderate-to-severe psoriasis (4:1) to three escalating doses of SRT2104, a selective activator of SIRT1, or placebo. Across all SRT2104 groups, 35% of patients (p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84 but was not consistently in agreement with PASI. Improvement in histology was associated with modulation of IL-17 and TNF-α signaling pathways and keratinocyte differentiation target genes. 27 subjects (69%) across all treatment groups, including placebo, experienced at least one treatment emergent adverse event. The majority of AEs were either mild or moderate. Most common were headache (8%), dizziness (8%), upper respiratory tract infection (8%), and psoriatic arthropathy (8%). Average drug exposure increased in a dose-dependent manner for escalating doses of SRT2104 and had high intra-subject variability in exposure (AUC %CV: 51–89%). Given the interesting signals of clinical activity, impact on gene expression and the generally favorable safety profile seen in this study, further investigation of SIRT1 activators for the treatment of psoriasis is warranted.

Trial Registration

Clinicaltrials.gov NCT01154101     

Two proton translocation pathways in a secondary active multidrug transporter

LmrP is a secondary active multidrug transporter from Lactococcus lactis. The protein belongs to the major facilitator superfamily and utilizes the electrochemical proton gradient (inside negative and alkaline) to extrude a wide range of lipophilic cations from the cell. Previous work has indicated that ethidium, a monovalent cationic substrate, is exported by LmrP by electrogenic antiport with two (or more) protons. This observation raised the question whether these protons are translocated sequentially along the same pathway, or through different routes. To address this question, we constructed a 3-D homology model of LmrP based on the high-resolution structure of the glycerol-3P/Pi antiporter GlpT from Escherichia coli, and we tested by mutagenesis the possible proton conduction points suggested by this model. Similar to the template, LmrP is predicted to contain an internal cavity formed at the interface between the two halves of the transporter. On the surface of this cavity lie two clusters of polar, aromatic and carboxylate residues with potentially important function in proton shuttling. Cluster 1 in the C-terminal half contains D235 and E327 in immediate proximity of each other, and is located near the apex of the cavity. Cluster 2 in the N-terminal half contains D142. Analyses of LmrP mutants containing charge-conservative or carboxyl-to-amide replacements at positions 142, 235 and 327 suggest that D142 is part of a dedicated proton translocation pathway in the ethidium translocation reaction. In contrast, D235 and E327 are part of an independent pathway, in which D235 interacts with protons. E327 appears to modulate the pKa of D235 and plays a role in the interaction with ethidium. These results are consistent with the proposal that major facilitator superfamily proteins consist of two membrane domains, one of which is involved in substrate binding and the other in ion coupling, and they indicate that there are two proton conduction pathways at play in the transport mechanism.     

Oil extraction from Scenedesmus obliquus using a continuous microwave system--design, optimization, and quality characterization

A 1.2 kW, 2450 MHz resonant continuous microwave processing system was designed and optimized for oil extraction from green algae (Scenedesmus obliquus). Algae-water suspension (1:1 w/w) was heated to 80 and 95°C, and subjected to extraction for up to 30 min. Maximum oil yield was achieved at 95°C and 30 min. The microwave system extracted 76-77% of total recoverable oil at 20-30 min and 95°C, compared to only 43-47% for water bath control. Extraction time and temperature had significant influence (p<0.0001) on extraction yield. Oil analysis indicated that microwaves extracted oil containing higher percentages of unsaturated and essential fatty acids (indicating higher quality). This study validates for the first time the efficiency of a continuous microwave system for extraction of lipids from algae. Higher oil yields, faster extraction rates and superior oil quality demonstrate this system's feasibility for oil extraction from a variety of feedstock.     

Physiological responses to acute experimental hypoxia in the air-breathing Indian catfish, Clarias batrachus (Linnaeus, 1758)

With an aim to study the mechanism of adaptation to acute hypoxic periods by hypoxia-tolerant catfish, Clarias batrachus, the mass-specific metabolic rate (VO₂) along with its hematological parameters, metabolic response and antioxidant enzyme activities were studied. During progressive hypoxia, C. batrachus was found to be an oxyconformer and showed a steady decline in its aquatic oxygen consumption rate. When C. batrachus was exposed for different periods at experimental hypoxia level (0.98?±?0.1 mg/L, DO), hemoglobin and hematocrit concentrations were increased, along with decrease in mean cellular hemoglobin concentration, which reflected a physiological adaptation to enhance oxygen transport capacity. Significant increase in serum glucose and lactate concentration as well as lactate dehydrogenase activity was observed. Antioxidant enzymes were found to operate independently of one another, while total glutathione concentration was unaffected in any of the tissues across treatments. These observations suggested that hypoxia resulted in the development of oxidative stress and C. batrachus was able to respond through increase in the oxygen carrying capacity, metabolic depression and efficient antioxidant defense system to survive periods of acute hypoxia.     

Fresh Water Cyanobacteria Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as an Anticancer Drug Resource

An increasing number of cancer patients worldwide, especially in third world countries, have raised concern to explore natural drug resources, such as the less explored fresh water filamentous cyanobacteria. Six strains of cyanobacteria (Phormidium sp. CCC727, Geitlerinema sp. CCC728, Arthrospira sp. CCC729, Phormidium sp. CCC731, Phormidium sp. CCC730, and Leptolyngbya sp. CCC732) were isolated (paddy fields and ponds in the Banaras Hindu University, campus) and five strains screened for anticancer potential using human colon adenocarcinoma (HT29) and human kidney adenocarcinoma (A498) cancer cell lines. Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 were the most potent as determined by examination of morphological features and by inhibition of growth by graded concentrations of crude extracts and thin-layer chromatography (TLC) eluates. Cell cycle analysis and multiplex assays using cancer biomarkers also confirmed Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as cancer drug resources. Apoptotic studies in the cells of A498 (cancer) and MCF-10A (normal human epithelial) exposed to crude extracts and TLC fractions revealed no significant impact on MCF-10A cells emphasizing its importance in the development of anticancer drug. Identification of biomolecules from these extracts are in progress.     

Influence of Soil Variation on Diosgenin Content Profile in Costus speciosus from Indo-Gangetic Plains

Costus speciosus is a rich source of commercially important compound Diosgenin, distributed in different regions of India. The present investigation was aimed to quantify diosgenin through High Performance Thin Layer Chromatography in 34 germplasms of Costus speciosus and also to identify the superior sources and to correlate the macronutrients of rhizospheric soil. The starch content varied in microscopic examination and correlated inversely (r=−0.266) with diosgenin content. Findings revealed that the extraction process with acid hydrolysis yielded higher diosgenin content (0.15–1.88 %) as compared to non-hydrolysis (0.009–0.368 %) procedure. Germplasms from Uttar Pradesh (NBCS-4), Jharkhand (NBCS-39) and Bihar (NBCS-2) were identified as elite chemotypes based on hierarchical clustering analysis. The phosphorous content of respective rhizospheric soil correlated positively (r=0.742) with diosgenin content. Findings of present study are useful to identify the new agrotechniques. The elite germplasms can also be used as quality planting material for large scale cultivation in order to assure a sustained supply to the herbal drug industry.