Indian Ocean glacial deoxygenation and respired carbon accumulation during mid-late Quaternary ice ages.

Reconstructions of ocean oxygenation are critical for understanding the role of respired carbon storage in regulating atmospheric CO2. Independent sediment redox proxies are essential to assess such reconstructions. Here, we present a long magnetofossil record from the eastern Indian Ocean in which we observe coeval magnetic hardening and enrichment of larger, more elongated, and less oxidized magnetofossils during glacials compared to interglacials over the last ~900 ka. Our multi-proxy records of redox-sensitive magnetofossils, trace element concentrations, and benthic foraminiferal Δδ13C consistently suggest a recurrence of lower O2 in the glacial Indian Ocean over the last 21 marine isotope stages, as has been reported for the Atlantic and Pacific across the last glaciation. Consistent multi-proxy documentation of this repeated oxygen decline strongly supports the hypothesis that increased Indian Ocean glacial carbon storage played a significant role in atmospheric CO2 cycling and climate change over recent glacial/interglacial timescales.

Comparative Transcriptomics Analysis of the Responses of the Filamentous Fungus Glarea lozoyensis to Different Carbon Sources.

The natural product pneumocandin B0 is the precursor of the antifungal drug caspofungin. We found that replacing glucose in the initial fermentation medium with 20 g/L fructose is more conducive to pneumocandin B0 production and biomass accumulation. In order to explore the mechanism of the different metabolic responses to fructose and glucose, we used each as the sole carbon source, and the results showed that fructose increased the total pneumocandin B0 yield and biomass by 54.76 and 13.71%, respectively. Furthermore, we analyzed the differences of gene expression and metabolic pathways between the two different carbon sources by transcriptomic analysis. When fructose was used as the carbon source, genes related to the pentose phosphate pathway (PPP), glycolysis and branched-chain amino acid metabolism were significantly upregulated, resulting in increased intracellular pools of NADPH and acetyl-CoA in Glarea lozoyensis for cell growth and pneumocandin B0 product synthesis. Interestingly, the pneumocandin B0 biosynthetic gene cluster and the genes of the TCA cycle were significantly downregulated, while the FAS genes were significantly upregulated, indicating that more acetyl-CoA was used for fatty acid synthesis. In particular, we found that excessive synthesis of fatty acids caused lipid accumulation, and lipid droplets can sequester lipophilic secondary metabolites such as pneumocandin B0 to reduce cell damage, which may also be an important reason for the observed increase of pneumocandin B0 yield. These results provide new insights into the relationship between pneumocandin B0 biosynthesis and carbon sources in G. lozoyensis. At the same time, this study provides important genomic information for improving pneumocandin B0 production through metabolic engineering strategies in the future.

Effect of SDS on release of intracellular pneumocandin B0 in extractive batch fermentation of Glarea lozoyensis.

Pneumocandin B0 is a hydrophobic secondary metabolite that accumulates in the mycelia of Glarea lozoyensis and inhibits fungal 1,3-ß-glucan synthase. Extractive batch fermentation can promote the release of intracellular secondary metabolites into the fermentation broth and is often used in industry. The addition of extractants has been proven as an effective method to attain higher accumulation of hydrophobic secondary metabolites and circumvent troublesome solvent extraction. Various extractants exerted significant but different influences on the biomass and pneumocandin B0 yields. The maximum pneumocandin B0 yield (2528.67 mg/L) and highest extracellular pneumocandin B0 yield (580.33 mg/L) were achieved when 1.0 g/L SDS was added on the 13th day of extractive batch fermentation, corresponding to significant increases of 37.63 and 154% compared with the conventional batch fermentation, respectively. The mechanism behind this phenomenon is partly attributed to the release of intracellular pneumocandin B0 into the fermentation broth and the enhanced biosynthesis of pneumocandin B0 in the mycelia.

1,25-Dihydroxyvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation.

BACKGROUND: Vitamin D3 has been known to have an anticancer effect, but the mechanisms underlying this is poorly explored. The present study aimed to investigate the antitumor role of vitamin D3 on gastric cancer and mechanisms. METHODS: The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D3 in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D3 on the proliferation of gastric cancer cells. After the identification of hypermethylation of BMP3 CpG islands by bisulfite genomic sequencing (BGS), we further investigated the relationship of BMP3 expression and gastric carcinogenesis by Western blot analysis and gel electrophoresis mobility shift assay (EMSA). RESULTS: Here we show that low concentration of 1, 25-dihydroxyvitamin D3 links to can-cerization and significantly inhibits proliferation of undifferentiated gastric cancer cell lines SGC-7901 and BGC-823. BMP3 promoter hypermethylation was highly correlated with gastric tumor. Moreover, BMP3 expression was regulated by its promoter methylation in gastric cells. The further exploration of the relationship between 1, 25-dihydroxyvitamin D3 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D3 stimulates BMP3 expression by the inhibition of BMP3 promoter methylation in gastric tumor cells. CONCLUSION: In combination with the data from clinical research, bioinformatics analysis and experimental verification, we propose that 1, 25-hydroxylvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation.

Enhancement of Pneumocandin B0 Production in Glarea lozoyensis by Low-Temperature Adaptive Laboratory Evolution.

The production of pneumocandin B0 is limited by feedback inhibition. Here, low-temperature adaptive laboratory evolution (ALE) was used to improve the production capacity of Glarea lozoyensis by enhancing its membrane permeability. After 50 cycles of ALE, the pneumocandin B0 production of the endpoint strain (ALE50) reached 2131 g/L, which was 32% higher than the starting strain (ALE0). ALE50 showed a changed fatty acid composition of the cell membrane, which-+h increased its permeability by 14%, which in turn increased the secretion ratio threefold. Furthermore, ALE50 showed increased intracellular proline and acetyl-CoA concentrations, superoxide dismutase (SOD), and catalase (CAT) activity, as well as total antioxidant capacity. The slight biomass decrease in ALE50 was accompanied by decreased isocitrate dehydrogenase (ICDH) and glucose-6-phosphate dehydrogenase (G6PDH) activity. Finally, a putative model of the accumulation and secretion of pneumocandin B0 in ALE50 was established. ALE is a promising method to release intracellular feedback inhibition.

Novel osmotic stress control strategy for improved pneumocandin B0 production in Glarea lozoyensis combined with a mechanistic analysis at the transcriptome level.

Pneumocandin B0, the precursor of the antifungal drug caspofungin, is a secondary metabolite of the fungus Glarea lozoyensis. In this study, we investigated the effects of mannitol as the sole carbon source on pneumocandin B0 production by G. lozoyensis. The osmotic pressure is more important in enhancing pneumocandin B0 production than is the substrate concentration. Based on the kinetic analysis, an osmotic stress control fed-batch strategy was developed. This strategy led to a maximum pneumocandin B0 concentration of 2711 mg/L with a productivity of 9.05 mg/L/h, representing 34.67 and 6.47% improvements, respectively, over the best result achieved by the one-stage fermentation. Furthermore, G. lozoyensis accumulated glutamate and proline as compatible solutes to resist osmotic stress, and these amino acids also provided the precursors for the enhanced pneumocandin B0 production. Osmotic stress also activated ROS (reactive oxygen species)-dependent signal transduction by upregulating the levels of related genes and increasing intracellular ROS levels by 20%. We also provided a possible mechanism for pneumocandin B0 accumulation based on signal transduction. These findings will improve our understanding of the regulatory mechanisms of pneumocandin B0 biosynthesis and may be applied to improve secondary metabolite production.

Acute toxic responses of embryo-larval zebrafish to zinc pyrithione (ZPT) reveal embryological and developmental toxicity.

Zinc pyrithione (ZPT) is widely used in industrial and human daily life, due to its broad antimicrobial spectrum activity. Persistent accumulation of ZTP in the aquatic environment and bioaccumulation in the living organisms attracts more and more attention. However, only very limited information is available so far for the evaluation of systematic toxicity effects of ZPT on multiple organs development. This study intends to deepen our knowledge about the potential toxicity elicited by ZPT by assessing its acute effects on zebrafish (Danio rerio) through morphological, histological and molecular investigations. It has been verified that ZPT exhibits a broad spectrum of toxicity which causes growth retardation and tissue pathological and physiology alternations in heart, liver, eye, notochord, kidney and other organisms of zebrafish. The acute toxicity values of LC50 (95% CI) 96-h is calculated as 0.073 µM. Furthermore, the organ toxicity was verified due to up-regulation of expression of biomarker genes related to organ function and development. In sum, this study demonstrats systematic acute embryological and developmental toxicity of the ZPT on zebrafish embryos/larvae.

A Novel Walking Detection and Step Counting Algorithm Using Unconstrained Smartphones.

Recently, with the development of artificial intelligence technologies and the popularity of mobile devices, walking detection and step counting have gained much attention since they play an important role in the fields of equipment positioning, saving energy, behavior recognition, etc. In this paper, a novel algorithm is proposed to simultaneously detect walking motion and count steps through unconstrained smartphones in the sense that the smartphone placement is not only arbitrary but also alterable. On account of the periodicity of the walking motion and sensitivity of gyroscopes, the proposed algorithm extracts the frequency domain features from three-dimensional (3D) angular velocities of a smartphone through FFT (fast Fourier transform) and identifies whether its holder is walking or not irrespective of its placement. Furthermore, the corresponding step frequency is recursively updated to evaluate the step count in real time. Extensive experiments are conducted by involving eight subjects and different walking scenarios in a realistic environment. It is shown that the proposed method achieves the precision of 93.76 % and recall of 93.65 % for walking detection, and its overall performance is significantly better than other well-known methods. Moreover, the accuracy of step counting by the proposed method is 95.74 % , and is better than both of the several well-known counterparts and commercial products.