Metagenomic analysis of gut microbial communities from a Central Asian population

OBJECTIVE: Changes in the gut microbiota are increasingly recognised to be involved in many diseases. This ecosystem is known to be shaped by many factors, including climate, geography, host nutrition, lifestyle and medication. Thus, knowledge of varying populations with different habits is important for a better understanding of the microbiome. DESIGN: We therefore conducted a metagenomic analysis of intestinal microbiota from Kazakh donors, recruiting 84 subjects, including male and female healthy subjects and metabolic syndrome (MetS) patients aged 25-75 years, from the Kazakh administrative centre, Astana. We characterise and describe these microbiomes, the first deep-sequencing cohort from Central Asia, in comparison with a global dataset (832 individuals from five countries on three continents), and explore correlations between microbiota, clinical and laboratory parameters as well as with nutritional data from Food Frequency Questionnaires. RESULTS: We observe that Kazakh microbiomes are relatively different from both European and East Asian counterparts, though similar to other Central Asian microbiomes, with the most striking difference being significantly more samples falling within the Prevotella-rich enterotype, potentially reflecting regional diet and lifestyle. We show that this enterotype designation remains stable within an individual over time in 82% of cases. We further observe gut microbiome features that distinguish MetS patients from controls (eg, significantly reduced Firmicutes to Bacteroidetes ratio, Bifidobacteria and Subdoligranulum, alongside increased Prevotella), though these overlap little with previously published reports and thus may reflect idiosyncrasies of the present cohort. CONCLUSION: Taken together, this exploratory study describes gut microbiome data from an understudied population, providing a starting point for further comparative work on biogeography and research on widespread diseases. TRIAL REGISTRATION NUMBER: ISRCTN37346212; Post-results

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism

The FuturICT education accelerator

Education is a major force for economic and social wellbeing. Despite high aspirations, education at all levels can be expensive and ineffective. Three Grand Challenges are identified: (1) enable people to learn orders of magnitude more effectively, (2) enable people to learn at orders of magnitude less cost, and (3) demonstrate success by exemplary interdisciplinary education in complex systems science. A ten year ‘man-on-the-moon’ project is proposed in which FuturICT’s unique combination of Complexity, Social and Computing Sciences could provide an urgently needed transdisciplinary language for making sense of educational systems. In close dialogue with educational theory and practice, and grounded in the emerging data science and learning analytics paradigms, this will translate into practical tools (both analytical and computational) for researchers, practitioners and leaders; generative principles for resilient educational ecosystems; and innovation for radically scalable, yet personalised, learner engagement and assessment. The proposed Education Accelerator will serve as a ‘wind tunnel’ for testing these ideas in the context of real educational programmes, with an international virtual campus delivering complex systems education exploiting the new understanding of complex, social, computationally enhanced organisational structure developed within FuturICT

The FuturICT education accelerator

Education is a major force for economic and social wellbeing. Despite high aspirations, education at all levels can be expensive and ineffective. Three Grand Challenges are identified: (1) enable people to learn orders of magnitude more effectively, (2) enable people to learn at orders of magnitude less cost, and (3) demonstrate success by exemplary interdisciplinary education in complex systems science. A ten year ‘man-on-the-moon’ project is proposed in which FuturICT’s unique combination of Complexity, Social and Computing Sciences could provide an urgently needed transdisciplinary language for making sense of educational systems. In close dialogue with educational theory and practice, and grounded in the emerging data science and learning analytics paradigms, this will translate into practical tools (both analytical and computational) for researchers, practitioners and leaders; generative principles for resilient educational ecosystems; and innovation for radically scalable, yet personalised, learner engagement and assessment. The proposed Education Accelerator will serve as a ‘wind tunnel’ for testing these ideas in the context of real educational programmes, with an international virtual campus delivering complex systems education exploiting the new understanding of complex, social, computationally enhanced organisational structure developed within FuturICT

The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying melanoma tumor development and progression are still not completely understood. One of the new candidates that emerged from a recent gene expression profiling study is <it>fatty acid-binding protein 7 </it>(<it>FABP7)</it>, involved in lipid metabolism, gene regulation, cell growth and differentiation.</p> <p>Methods</p> <p>We studied the functional role of FABP7 in human melanoma cell lines and using immunohistochemistry analyzed its expression pattern and clinical role in 11 nevi, 149 primary melanomas and 68 metastases.</p> <p>Results</p> <p>FABP7 mRNA and protein level is down-regulated following treatment of melanoma cell lines with a PKC activator (PMA) or MEK1 inhibitor (PD98059). Down-regulation of FABP7 using siRNA decreased cell proliferation and invasion but did not affect apoptosis. In clinical specimens, FABP7 was expressed in 91% of nevi, 71% of primary melanomas and 70% of metastases, with a cytoplasmic and/or nuclear localization. FABP7 expression was associated with tumor thickness in superficial spreading melanoma (P = 0.021). In addition, we observed a trend for an association between FABP7 expression and Ki-67 score (P = 0.070) and shorter relapse-free survival (P = 0.069) in this group of patients.</p> <p>Conclusion</p> <p>Our data suggest that FABP7 can be regulated by PKC and the MAPK/ERK1/2 pathway through independent mechanisms in melanoma cell lines. Furthermore, FABP7 is involved in cell proliferation and invasion <it>in vitro</it>, and may be associated with tumor progression in melanoma.</p

Towards standards for human fecal sample processing in metagenomic studies

Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation and sample storage, which we contrasted with observed biological variation within the same specimen or within an individual over time. We found that DNA extraction had the largest effect on the outcome of metagenomic analysis. To rank DNA extraction protocols, we considered resulting DNA quantity and quality, and we ascertained biases in estimates of community diversity and the ratio between Gram-positive and Gram-negative bacteria. We recommend a standardized DNA extraction method for human fecal samples, for which transferability across labs was established and which was further benchmarked using a mock community of known composition. Its adoption will improve comparability of human gut microbiome studies and facilitate meta-analyses

Langmuir probe electronics upgrade on the tokamak a configuration variable

A detailed description of the Langmuir probe electronics upgrade for TCV (Tokamak a Configuration Variable) is presented. The number of amplifiers and corresponding electronics has been increased from 48 to 120 in order to simultaneously connect all of the 114 Langmuir probes currently mounted in the TCV divertor and main-wall tiles. Another set of 108 amplifiers is ready to be installed in order to connect 80 new probes, built in the frame of the TCV divertor upgrade. Technical details of the amplifier circuitry are discussed as well as improvements over the first generation of amplifiers developed at SPC (formerly CRPP) in 1993/1994 and over the second generation developed in 2012/2013. While the new amplifiers have been operated successfully for over a year, it was found that their silicon power transistors can be damaged during some off-normal plasma events. Possible solutions are discussed. (C) 2019 Author(s)