Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The ...largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.
Dietary fibre positively influences gut microbiome composition, enhancing the metabolism of dietary flavonoids to produce bioactive metabolites. These synergistic activities facilitate the beneficial ...effects of dietary flavonoids on cardiometabolic health parameters. The aims of this study were to investigate whether isoquercetin (a major dietary flavonoid) and inulin (soluble fibre), either alone or in combination could improve features of the metabolic syndrome. Following a 1 week acclimatization, male C57BL6 mice (6-8 weeks) were randomly assigned to; (i) normal chow diet (n = 10), (ii) high fat (HF) diet (n = 10), (iii) HF diet + 0.05% isoquercetin (n = 10), (iv) HF diet + 5% inulin, or (v) HF diet + 0.05% isoquercetin + 5% inulin (n = 10). Body weight and food intake were measured weekly. At 12 weeks, glucose and insulin tolerance tests were performed, and blood, faecal samples, liver, skeletal muscle and adipose tissue were collected. At 12 weeks, mice on the HF diet had significantly elevated body weights as well as impaired glucose tolerance and insulin sensitivity compared to the normal chow mice. Supplementation with either isoquercetin or inulin had no effect, however mice receiving the combination had attenuated weight gain, improved glucose tolerance and insulin sensitivity, reduced hepatic lipid accumulation, adipocyte hypertrophy, circulating leptin and adipose FGF21 levels, compared to mice receiving the HF diet. Additionally, mice on the combination diet had improvements in the composition and functionality of their gut microbiome as well as production of short chain fatty acids. In conclusion, long-term supplementation with the dietary flavonoid isoquercetin and the soluble fibre inulin can attenuate development of the metabolic syndrome in mice fed a high fat diet. This protective effect appears to be mediated, in part, through beneficial changes to the microbiome.
The K2 Mission: Characterization and Early Results Howell, Steve B.; Sobeck, Charlie; Haas, Michael ...
Publications of the Astronomical Society of the Pacific,
04/2014, Letnik:
126, Številka:
938
Journal Article
Recenzirano
Odprti dostop
The K2 mission will make use of the Kepler spacecraft and its assets to expand upon Kepler's groundbreaking discoveries in the fields of exoplanets and astrophysics through new and exciting ...observations. K2 will use an innovative way of operating the spacecraft to observe target fields along the ecliptic for the next 2-3 years. Early science commissioning observations have shown an estimated photometric precision near 400 ppm in a single 30 minute observation, and a 6-hr photometric precision of 80 ppm (both at V = 12). The K2 mission offers long-term, simultaneous optical observation of thousands of objects at a precision far better than is achievable from ground-based telescopes. Ecliptic fields will be observed for approximately 75 days enabling a unique exoplanet survey which fills the gaps in duration and sensitivity between the Kepler and TESS missions, and offers pre-launch exoplanet target identification for JWST transit spectroscopy. Astrophysics observations with K2 will include studies of young open clusters, bright stars, galaxies, supernovae, and asteroseismology.
During tumor growth—when nutrient and anabolic demands are high—autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling. Ras‐driven tumors ...additionally invoke non‐autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well‐characterized malignant tumor model in Drosophila melanogaster. Micro‐computed X‐ray tomography and metabolic profiling reveal that RasV12; scrib−/− tumors grow 10‐fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, ‐motility, ‐feeding, and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth.
Synopsis
Autophagy maintains mitochondrial health and nutrient recycling in tumor cells, and promotes the transfer of amino acids from microenvironmental to tumor cells, thereby sustaining tumor metabolism and growth. In this study, X‐ray tomography, metabolomics and carbon tracing reveal that autophagy‐mediated wasting of distal tissues provides amino acids and sugars that increase eye tumor biomass in Drosophila melanogaster.
RasV12, scrib−/− tumors induce organ wasting and cause release of amino acids and sugar into circulation.
Systemic autophagy mediates muscle wasting and nutrient release.
Tumor biomass increasingly derive from host tissues as wasting ensues.
X‐ray tomography, metabolomics and carbon tracing reveal that autophagy‐mediated wasting of distal tissues provides amino acids and sugars that increase eye tumor biomass in Drosophila melanogaster.
Although cochlear implants work well for people with hearing impairment in quiet conditions, it is well-known that they are not as effective in noisy environments. Noise reduction algorithms based on ...machine learning allied with appropriate speech features can be used to address this problem. The purpose of this study is to investigate the importance of acoustic features in such algorithms. Acoustic features are extracted from speech and noise mixtures and used in conjunction with the ideal binary mask to train a deep neural network to estimate masks for speech synthesis to produce enhanced speech. The intelligibility of this speech is objectively measured using metrics such as Short-time Objective Intelligibility (STOI), Hit Rate minus False Alarm Rate (HIT-FA) and Normalized Covariance Measure (NCM) for both simulated normal-hearing and hearing-impaired scenarios. A wide range of existing features is experimentally evaluated, including features that have not been traditionally applied in this application. The results demonstrate that frequency domain features perform best. In particular, Gammatone features performed best for normal hearing over a range of signal-to-noise ratios and noise types (STOI = 0.7826). Mel spectrogram features exhibited the best overall performance for hearing impairment (NCM = 0.7314). There is a stronger correlation between STOI and NCM than HIT-FA and NCM, suggesting that the former is a better predictor of intelligibility for hearing-impaired listeners. The results of this study may be useful in the design of adaptive intelligibility enhancement systems for cochlear implants based on both the noise level and the nature of the noise (stationary or non-stationary).
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic representation of the metabolic disorders. Inorganic nitrate/nitrite can be converted to nitric oxide, regulate glucose metabolism, ...lower lipid levels, and reduce inflammation, thus raising the hypothesis that inorganic nitrate/nitrite could be beneficial for improving NAFLD. This study assessed the therapeutic effects of chronic dietary nitrate on NAFLD in a mouse model. 60 ApoE−/- mice were fed a high-fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis with associated NAFLD. The mice were then randomly assigned to different groups (20/group) for a further 12 weeks: (i) HFD + NaCl (1 mmol/kg/day), (ii) HFD + NaNO3 (1 mmol/kg/day), and (iii) HFD + NaNO3 (10 mmol/kg/day). A fourth group of ApoE−/- mice consumed a normal chow diet for the duration of the study. At the end of the treatment, caecum contents, serum, and liver were collected. Consumption of the HFD resulted in significantly greater lipid accumulation in the liver compared to mice on the normal chow diet. Mice whose HFD was supplemented with dietary nitrate for the second half of the study, showed an attenuation in hepatic lipid accumulation. This was also associated with an increase in hepatic AMPK activity compared to mice on the HFD. In addition, a significant difference in bile acid profile was detected between mice on the HFD and those receiving the high dose nitrate supplemented HFD. In conclusion, dietary nitrate attenuates the progression of liver steatosis in ApoE−/- mice fed a HFD.
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