Hypoxia-inducible transcription factor-1α promotes hypoxia-induced A549 apoptosis via a mechanism that involves the glycolysis pathway

BACKGROUND: Hypoxia-inducible transcription factor-1α (HIF-1α), which plays an important role in controlling the hypoxia-induced glycolysis pathway, is a "master" gene in the tissue hypoxia response during tumor development. However, its role in the apoptosis of non-small cell lung cancer remains unknown. Here, we have studied the effects of HIF-1α on apoptosis by modulating HIF-1α gene expression in A549 cells through both siRNA knock-down and over-expression. METHODS: A549 cells were transfected with a HIF-1α siRNA plasmid or a HIF-1α expression vector. Transfected cells were exposed to a normoxic or hypoxic environment in the presence or absence of 25 mM HEPES and 2-deoxyglucose (2-DG) (5 mM). The expression of three key genes of the glycolysis pathway, glucose transporter type 1(GLUT1), phosphoglycerate kinase 1(PGK1), and hexokinase 1(HK1), were measured using real-time RT-PCR. Glycolysis was monitored by measuring changes of pH and lactate concentration in the culture medium. Apoptosis was detected by TUNEL assay and flow cytometry. RESULTS: Knocking down expression of HIF-1α inhibited the glycolysis pathway, increased the pH of the culture medium, and protected the cells from hypoxia-induced apoptosis. In contrast, over-expression of HIF-1α accelerated glycolysis in A549 cells, decreased the pH of the culture medium, and enhanced hypoxia-induced apoptosis. These effects of HIF-1α on glycolysis, pH of the medium, and apoptosis were reversed by treatment with the glycolytic inhibitor, 2-DG. Apoptosis induced by HIF-1α over-expression was partially inhibited by increasing the buffering capacity of the culture medium by adding HEPES. CONCLUSION: During hypoxia in A549 cells, HIF-1α promotes activity of the glycolysis pathway and decreases the pH of the culture medium, resulting in increased cellular apoptosis

Spatial analysis of malaria in Anhui province, China

<p>Abstract</p> <p>Background</p> <p>Malaria has re-emerged in Anhui Province, China, and this province was the most seriously affected by malaria during 2005–2006. It is necessary to understand the spatial distribution of malaria cases and to identify highly endemic areas for future public health planning and resource allocation in Anhui Province.</p> <p>Methods</p> <p>The annual average incidence at the county level was calculated using malaria cases reported between 2000 and 2006 in Anhui Province. GIS-based spatial analyses were conducted to detect spatial distribution and clustering of malaria incidence at the county level.</p> <p>Results</p> <p>The spatial distribution of malaria cases in Anhui Province from 2000 to 2006 was mapped at the county level to show crude incidence, excess hazard and spatial smoothed incidence. Spatial cluster analysis suggested 10 and 24 counties were at increased risk for malaria (<it>P </it>< 0.001) with the maximum spatial cluster sizes at < 50% and < 25% of the total population, respectively.</p> <p>Conclusion</p> <p>The application of GIS, together with spatial statistical techniques, provide a means to quantify explicit malaria risks and to further identify environmental factors responsible for the re-emerged malaria risks. Future public health planning and resource allocation in Anhui Province should be focused on the maximum spatial cluster region.</p

Memory-enhancing effect of Rhodiola rosea L extract on aged mice

Purpose: The memory-enhancing effects of Rhodiola rosea L. extract (RRLE) on normal aged mice were assessed.Methods: In the open-field test, the effect of RRLE (150 and 300 mg/kg) on mouse locomotive activities was evaluated by investigating the extract’s influence on CAT and AchE activities in the brain tissue of mice.Results: Compared with aged group, high dose of RRLE reduced the total distance (3212.4 ± 123.1 cm, p &lt; 0.05) significantly, increased catalase (CAT) activity (101.4 ± 12.2 U/mg pro, p &lt; 0.05), and inhibited acetyl cholinesterase (AChE) activity (0.94 ± 0.12 U/mg pro, p &lt; 0.05) in the brain tissue of aged mice.Conclusion: The results show that RRLE improves the memory functions of aged mice probably by increasing CAT activity while decreasing AChE activity.Keywords: Rhodiola rosea, Memory function, Catalase, Acetyl cholinesterase, Open-field tes

D5.2 - Evaluation of Selected Measurement-based Techniques

Deliverable D5.2 del projecte FARAMIRPreprin

The silicon isotope composition of Ethmodiscus rexlaminated diatom mats from the tropical West Pacific: Implications for silicate cycling during the Last Glacial Maximum

The cause of massive blooms of Ethmodiscus rex laminated diatom mats (LDMs) in the eastern Philippine Sea (EPS) during the Last Glacial Maximum (LGM) remains uncertain. In order to better understand the mechanism of formation of E. rex LDMs from the perspective of dissolved silicon (DSi) utilization, we determined the silicon isotopic composition of single E. rex diatom frustules (δ30SiE. rex) from two sediment cores in the Parece Vela Basin of the EPS. In the study cores, δ30SiE. rex varies from −1.23‰ to −0.83‰ (average −1.04‰), a range that is atypical of marine diatom δ30Si and that corresponds to the lower limit of reported diatom δ30Si values of any age. A binary mixing model (upwelled silicon versus eolian silicon) accounting for silicon isotopic fractionation during DSi uptake by diatoms was constructed. The binary mixing model demonstrates that E. rex dominantly utilized DSi from eolian sources (i.e., Asian dust) with only minor contributions from upwelled seawater sources (i.e., advected from Subantarctic Mode Water, Antarctic Intermediate Water, or North Pacific Intermediate Water). E. rex utilized only ~24% of available DSi, indicating that surface waters of the EPS were eutrophic with respect to silicon during the LGM. Our results suggest that giant diatoms did not always use a buoyancy strategy to obtain nutrients from the deep nutrient pool, thus revising previously proposed models for the formation of E. rex LDMs