Lithium-Induced Neuroprotection is Associated with Epigenetic Modification of Specific BDNF Gene Promoter and Altered Expression of Apoptotic-Regulatory Proteins

Bipolar disorder (BD), one of the most debilitating mental disorders, is associated with increased morbidity and mortality. Lithium is the first line of treatment option for BD and is often used for maintenance therapy. Recently, the neuroprotective action of lithium has gained tremendous attention, given that BD is associated with structural and functional abnormalities of the brain. However, the precise molecular mechanism by which lithium exerts its neuroprotective action is not clearly understood. In hippocampal neurons, the effects of lithium on neuronal viability against glutamate-induced cytotoxicity, dendritic length and number, and expression and methylation of BDNF promoter exons and expression of apoptotic regulatory genes were studied. In rat hippocampal neurons, lithium not only increased dendritic length and number, but also neuronal viability against glutamate-induced cytotoxicity. While lithium increased the expression of BDNF as well as genes associated with neuroprotection such as Bcl2 and Bcl-XL, it decreased the expression of pro-apoptotic genes Bax, Bad, and caspases 3. Interestingly, lithium activated transcription of specific exon IV to induce BDNF gene expression. This was accompanied by hypomethylation of BDNF exon IV promoter. This study delineates mechanisms by which lithium mediates its effects in protecting neurons

Current Status and Outlook in the Application of Microalgae in Biodiesel Production and Environmental Protection

Microalgae have been currently recognized as one group of the most potential feedstocks for biodiesel production due to high productivity potential, efficient biosynthesis of lipids and less competition with food production. Moreover, utilization of microalgae with environmental purposes (CO2 fixation, NOX and wastewater treatment) and biorefinery have been reported. However, there are still challenges that need to be addressed to ensure stable large-scale production with positive net energy balance. This review gives an overview of the current status of the application of microalgae in biodiesel production and environmental protection. The practical problems not only facing the microalgae biodiesel production but also associated with microalgae application for environmental pollution control, in particular biological fixation of greenhouse gas (CO2 and NOX) and wastewater treatment are described in detail. Notably, the synergistic combination of various applications (e.g. food, medicine, wastewater treatment and flue gas treatment) with biodiesel production could enhance the sustainability and economics of the algal biodiesel production system

Candidate genes involved in the biosynthesis of triterpenoid saponins in Platycodon grandiflorum identified by transcriptome analysis

Background: Platycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable.Principal Findings:A total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80%) were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant.Conclusion:The genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level

The K-segments of wheat dehydrin WZY2 are essential for its protective functions under temperature stress

Dehydrins (DHNs), group 2 of late embryogenesis abundant (LEA) proteins, are up-regulated in most plants during cold, drought, heat or salinity stress. All DHNs contain at least one K-segment, which is believed to play a significant role in DHN function by forming an amphipathic helix. In previous studies, wzy2, an YSK2-type DHN gene, was isolated from the Zhengyin 1 cultivar of Triticum aestivum under cold and drought stress treatment conditions. Four WZY2 truncated derivatives were constructed to knock out the K-, Y- or S-segment, which potentially affect the function of the protein. In vivo assays of Escherichia coli viability enhancement, in vitro lactate dehydrogenase (LDH) activity protection and ex vivo protein aggregation prevention assays revealed that WZY2 acted as a protectant and improved stress tolerance during temperature variation. The results also showed that unlike the truncated derivative without K-segments, the derivative containing two K-segments had remarkable effects that were similar to those of full-length WZY2, indicating that the K-segment is the major functional component of WZY2. Moreover, compared with the other segments, the first K-segment might be the most critical contributor to WZY2 functionality. In general, this work highlights the behavior of DHNs in relieving cold stress ex vivo and the contribution of the K-segment to DHN function

Effectiveness of an anti-algal compound in eliminating an aquatic unicellular harmful algal Phaeocystis globosa

Phaeocystis globosa blooms can have negative effects on higher trophic levels in the marine ecosystem and consequently influence human activities. Strain KA22, identified as the bacterium Hahella, was isolated from coastal surface water and used to control P. globosa growth. A methanol extract from the bacteral cells showed strong algicidal activity. After purification, the compound showed a similar structure to prodigiosin when identified with Q-Exactive Orbitrap MS and nuclear magnetic resonance spectra. The compound showed algicidal activity against P. globosa with a 50% Lethal Dose (LD50) of 2.24 μg/mL. The prodigiosin was stable under heat and acid environment, and it could be degraded under alkaline environment and natural light condition. The growth rates of strain KA22 was fast in 2216E medium and the content of prodigiosin in this medium was more than 70 μg/mL after 16 h incubation. The compound showed particularly strong algicidal activity against Prorocentrum donghaiense, P. globosa and Heterosigma akashiwo, but having little effect on three other phytoplankton species tested. The results of our research could increase our knowledge on harmful algal bloom control compound and lead to further study on the mechanisms of the lysis effect on harmful algae

Effects of curcumin on ion channels and transporters

Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a polyphenolic compound isolated from the rhizomes of Curcuma longa (turmeric), has been shown to exhibit a wide range of pharmacological activities including anti-inflammatory, anti-cancer, anti-oxidant, anti-atherosclerotic, anti-microbial, and wound healing effects. These activities of curcumin are based on its complex molecular structure and chemical features, as well as its ability to interact with multiple signaling molecules. The ability of curcumin to regulate ion channels and transporters was recognized a decade ago. The cystic fibrosis transmembrane conductance regulator (CFTR) is a well-studied ion channel target of curcumin. During the process of studying its anti-cancer properties, curcumin was found to inhibit ATP-binding cassette (ABC) family members including ABCA1, ABCB1, ABCC1, and ABCG2. Recent studies have revealed that many channels and transporters are modulated by curcumin, such as voltage-gated potassium (Kv) channels, high-voltage-gated Ca(2+) channels (HVGCC), volume-regulated anion channel (VRAC), Ca(2+) release-activated Ca(2+) channel (CRAC), aquaporin-4 (AQP-4), glucose transporters, etc., In this review, we aim to provide an overview of the interactions of curcumin with different types of ion channels and transporters and to help better understand and integrate the underlying molecular mechanisms of the multiple pharmacological activities of curcumin

Improved Productivity of Neutral Lipids in Chlorella sp. A2 by Minimal Nitrogen Supply

Nitrogen starvation is an efficient environmental pressure for increasing lipid accumulation in microalgae, but it could also significantly lower the biomass productivity, resulting in lower lipid productivity. In this study, green alga Chlorella sp. A2 was cultivated by using a minimal nitrogen supply strategy under both laboratory and outdoor cultivation conditions to evaluate biomass accumulation and lipid production. Results showed that minimal nitrogen supply could promote neutral lipid accumulation of Chlorella sp. A2 without a significant negative effect on cell growth. In laboratory cultivation mode, alga cells cultured with 18 mg L-1 d-1 urea addition could generate 74% and 416% (w/w) more neutral lipid productivity than cells cultured with regular BG11 and nitrogen starvation media, respectively. In outdoor cultivation mode, lipid productivity of cells cultured with 18 mg L-1 d-1 urea addition is approximately 10% and 88% higher than the one with regular BG11 and nitrogen starvation media, respectively. Notably, the results of photosynthetic analysis clarified that minimal nitrogen supply reduced the loss of photosynthetic capacity to keep CO2 fixation during photosynthesis for biomass production. The minimal nitrogen supply strategy for microalgae cultivation could promote neutral lipid accumulation without a significant negative effect on cell growth, resulting in a significant improvement in the lipid productivity

The dampening effect of employees’ future orientation on cyberloafing behaviors: The mediating role of self-control

Previous studies on reducing employees’ cyberloafing behaviors have primarily examined the external control factors but seldomly taken individual internal subjective factors into consideration. Future orientation, an important individual factor, is defined as the extent to which one plans for future time and considers future consequences of one’s current behavior. To explore further whether and how employees’ future orientation can dampen their cyberloafing behaviors, two studies were conducted to examine the relationship between employees’ future orientation and cyberloafing behaviors. The mediation effect of employees’ objective and subjective self-control between them was also examined. In Study 1, a set of questionnaires was completed, and the results revealed that the relationship between employees’ future orientation and cyberloafing behaviors was negative, and objective self-control mediated the relationship. Next, we conducted a priming experiment (Study 2) to examine the causal relationship and psychological mechanism between employees’ future orientation and cyberloafing behaviors. The results demonstrated that employees’ future-orientation dampened their attitudes and intentions to engage in cyberloafing, and subjective self-control mediated this dampening effect. Theoretical and practical implications of these findings are also discussed

A putative mitochondrial iron transporter MrsA in Aspergillus fumigatus plays important roles in azole-, oxidative stress responses and virulence

Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus

Maturation Along White Matter Tracts in Human Brain Using a Diffusion Tensor Surface Model Tract-Specific Analysis

Previous diffusion tensor imaging (DTI) tractography studies have demonstrated exponential patterns of developmental changes for diffusion parameters such as fractional anisotropy (FA) and mean diffusivity (MD) averaged over all voxels in major white matter (WM) tracts of the human brain. However, this assumes that the entire tract is changing in unison, which may not be the case. In this study, a surface model based tract specific analysis was applied to a cross-sectional cohort of 178 healthy subjects (83 males/95 females) aged from 6 to 30 years to spatially characterize the age-related changes of FA and MD along the trajectory of 7 major WM tracts – corpus callosum and 6 bilateral tracts. There were unique patterns of regions that showed different exponential and linear rates of increasing FA or decreasing MD and peak maturation age along each tract. Faster FA-development rate was observed in genu of corpus callosum (CC) and frontal-parietal part of superior longitudinal fasciculus (SLF). Inferior corticospinal tract (CST), posterior regions of association tracts such as inferior longitudinal fasciculus, inferior frontal fasciculus and uncinate fasciculus also displayed an early developmental pattern for FA. MD decreases with age also exhibited this posterior-to-anterior WM maturation pattern for most tracts in females. Both males and females displayed similar maturation patterns along most large tracts; however, males had overall delayed maturation peaks compared with females in most tracts with the greater differences occurring in the CST and frontal-parietal part of SLF for MD. Therefore, brain white matter development has spatially-varying trajectories along tracts that depend on sex and the tract