Different oat ingredients stimulate specific microbial metabolites in the gut microbiome of three human individuals in vitro

We used a standardized in vitro simulation of the intestinal environment of three human donors to investigate the effect of six oat ingredients, which were produced by the application of different processing techniques, on the gut microbial community. Fructooligosaccharide was used as the positive control. Consistent changes in pH and gas production, on average -0.4 pH units and +32 kPa, indicated the high fermentability of the oat ingredients, land the resulting increased production of metabolites that are considered as beneficial for human health. These metabolites included acetate and lactate, but mostly propionate (+13.6 mM on average). All oat ingredients resulted in increased bifidobacteria levels with an average increase of 0.73 log. Moreover, a decreased production of proteolytic markers was observed including branched short-chain fatty acids and ammonium. The results were donor-specific and product-specific. The results suggested an association between the total amounts of dietary fiber and the prebiotic potentials of different ingredients. Furthermore, as mechanical processing of oat products has previously been linked to increased extractability of dietary fibers, the obtained results suggest that different processing techniques might have impacted the potential functional properties of the final ingredients

Myotis rufoniger genome sequence and analyses: M-rufoniger's genomic feature and the decreasing effective population size of Myotis bats

Myotis rufoniger is a vesper bat in the genus Myotis. Here we report the whole genome sequence and analyses of the M. rufoniger. We generated 124 Gb of short-read DNA sequences with an estimated genome size of 1.88 Gb at a sequencing depth of 66x fold. The sequences were aligned to M. brandtii bat reference genome at a mapping rate of 96.50% covering 95.71% coding sequence region at 10x coverage. The divergence time of Myotis bat family is estimated to be 11.5 million years, and the divergence time between M. rufoniger and its closest species M. davidii is estimated to be 10.4 million years. We found 1,239 function-altering M. rufoniger specific amino acid sequences from 929 genes compared to other Myotis bat and mammalian genomes. The functional enrichment test of the 929 genes detected amino acid changes in melanin associated DCT, SLC45A2, TYRP1, and OCA2 genes possibly responsible for the M. rufoniger's red fur color and a general coloration in Myotis. N6AMT1 gene, associated with arsenic resistance, showed a high degree of function alteration in M. rufoniger. We further confirmed that the M. rufoniger also has batspecific sequences within FSHB, GHR, IGF1R, TP53, MDM2, SLC45A2, RGS7BP, RHO, OPN1SW, and CNGB3 genes that have already been published to be related to bat's reproduction, lifespan, flight, low vision, and echolocation. Additionally, our demographic history analysis found that the effective population size of Myotis clade has been consistently decreasing since similar to 30k years ago. M. rufoniger's effective population size was the lowest in Myotis bats, confirming its relatively low genetic diversity

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

Korea

NAND flash memory can provide cost-effective secondary storage in mobile embedded systems, but its lack of a random access capability means that code shadowing is generally required, taking up extra RAM space. Demand paging with NAND flash memory has recently been proposed as an alternative which requires less RAM. This scheme is even more attractive for OneNAND flash, which consists of a NAND flash array with SRAM buffers, and supports eXecute-In-Place (XIP), which allows limited random access to data on the SRAM buffers. We introduce a novel demand paging method for OneNAND flash memory with XIP feature. The proposed on-line demand paging method with XIP adopts finite size sliding window to capture the paging history and thus predict future page demands. We particularly focus on non-critical code accesses which can disturb real-time code. Experimental results show that our method outperforms conventional LRU-based demand paging by 57 % in terms of execution time and by 63 % in terms of energy consumption. It even beats the optimal solution obtained from MIN, which is a conventional off-line demand paging technique by 30 % and 40 % respectively

Let Nagasaki Be the Last! Nineteen Pandemic-Nuclear Nexus Policy Measures in Northeast Asia

In October–November 2020, RECNA-Nagasaki University and Asia-Pacific Leadership Network (APLN) with the support of Nautilus Institute convened the Nagasaki 75th Anniversary scenario workshop to address the pandemic-nuclear nexus. About fifty participants of diverse background explored the future of nuclear war and nuclear disarmament in light of the uncertainty created by the global coronavirus pandemic. Their specific task was to develop four scenarios to identify the opportunities driven by global pandemics for Northeast Asian governments, civil society and market actors to reduce nuclear risk and resume nuclear disarmament. Based on these scenarios, the workshop recommended sixteen urgent steps that could be implemented globally and in particular, in Northeast Asia. With three more policy measures added after the workshop, this article elaborates nineteen policy recommendations

Quantitative Proteomics Identifies a beta-Catenin Network as an Element of the Signaling Response to Frizzled-8 Protein-Related Antiproliferative Factor

Antiproliferative factor (APF), a Frizzled-8 protein-related sialoglycopeptide involved in the pathogenesis of interstitial cystitis, potently inhibits proliferation of normal urothelial cells as well as certain cancer cells. To elucidate the molecular mechanisms of the growth-inhibitory effect of APF, we performed stable isotope labeling by amino acids in cell culture analysis of T24 bladder cancer cells treated with and without APF. Among over 2000 proteins identified, 54 were significantly up-regulated and 48 were down-regulated by APF treatment. Bioinformatic analysis revealed that a protein network involved in cell adhesion was substantially altered by APF and that beta-catenin was a prominent node in this network. Functional assays demonstrated that APF down-regulated beta-catenin, at least in part, via proteasomal and lysosomal degradation. Moreover, silencing of beta-catenin mimicked the antiproliferative effect of APF whereas ectopic expression of nondegradable beta-catenin rescued growth inhibition in response to APF, confirming that beta-catenin is a key mediator of APF signaling. Notably, the key role of beta-catenin in APF signaling is not restricted to T24 cells, but was also observed in an hTERT-immortalized human bladder epithelial cell line, TRT-HU1. In addition, the network model suggested that beta-catenin is linked to cyclooxygenase-2 (COX-2), implying a potential connection between APF and inflammation. Functional assays verified that APF increased the production of prostaglandin E(2) and that down-modulation of beta-catenin elevated COX-2 expression, whereas forced expression of nondegradable beta-catenin inhibited APF-induced up-regulation of COX-2. Furthermore, we confirmed that beta-catenin was down-regulated whereas COX-2 was up-regulated in epithelial cells explanted from IC bladder biopsies compared with control tissues. In summary, our quantitative proteomics study describes the first provisional APF-regulated protein network, within which beta-catenin is a key node, and provides new insight that targeting the beta-catenin signaling pathway may be a rational approach toward treating interstitial cystitis. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.007492, 1-11, 2011.X11934sciescopu

Quantitative Proteomics Identifies a β-Catenin Network as an Element of the Signaling Response to Frizzled-8 Protein-Related Antiproliferative Factor*

Antiproliferative factor (APF), a Frizzled-8 protein-related sialoglycopeptide involved in the pathogenesis of interstitial cystitis, potently inhibits proliferation of normal urothelial cells as well as certain cancer cells. To elucidate the molecular mechanisms of the growth-inhibitory effect of APF, we performed stable isotope labeling by amino acids in cell culture analysis of T24 bladder cancer cells treated with and without APF. Among over 2000 proteins identified, 54 were significantly up-regulated and 48 were down-regulated by APF treatment. Bioinformatic analysis revealed that a protein network involved in cell adhesion was substantially altered by APF and that β-catenin was a prominent node in this network. Functional assays demonstrated that APF down-regulated β-catenin, at least in part, via proteasomal and lysosomal degradation. Moreover, silencing of β-catenin mimicked the antiproliferative effect of APF whereas ectopic expression of nondegradable β-catenin rescued growth inhibition in response to APF, confirming that β-catenin is a key mediator of APF signaling. Notably, the key role of β-catenin in APF signaling is not restricted to T24 cells, but was also observed in an hTERT-immortalized human bladder epithelial cell line, TRT-HU1. In addition, the network model suggested that β-catenin is linked to cyclooxygenase-2 (COX-2), implying a potential connection between APF and inflammation. Functional assays verified that APF increased the production of prostaglandin E2 and that down-modulation of β-catenin elevated COX-2 expression, whereas forced expression of nondegradable β-catenin inhibited APF-induced up-regulation of COX-2. Furthermore, we confirmed that β-catenin was down-regulated whereas COX-2 was up-regulated in epithelial cells explanted from IC bladder biopsies compared with control tissues. In summary, our quantitative proteomics study describes the first provisional APF-regulated protein network, within which β-catenin is a key node, and provides new insight that targeting the β-catenin signaling pathway may be a rational approach toward treating interstitial cystitis

From proto-missional to mega-church: A critique of ecclesial ‘growth’ in Korea

In the last couple of decades, the Korean church experienced a loss of credibility as well as a decrease in membership. The premise of this contribution is that the mega-church phenomenon in Korea contributed to this state of affairs. Many Korean churches, influenced by dramatic sociopolitical and economic changes, developed a distorted understanding of its nature and mission. Korean churches began to compete against each other to grow bigger. An institutional ecclesiology and ecclesiocentric understanding of mission formed the basis of this endeavour. To counter this tendency, some churches turned to missional ecclesiology to facilitate the reformation of the Korean church. According to empirical data, Korean society rates mega-churches negatively while they evaluate missional churches positively. This provided further impetus for the current emerging missional movement in Korea

Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks

BackgroundThe aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.MethodsA 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).ResultsDuring the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.ConclusionOur results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo

Integrative epigenetic taxonomy of primary prostate cancer

\u3cp\u3eThe Androgen Receptor (AR) is the key-driving transcription factor in prostate cancer, tightly controlled by epigenetic regulation. To date, most epigenetic profiling has been performed in cell lines or limited tissue samples. Here, to comprehensively study the epigenetic landscape, we perform RNA-seq with ChIP-seq for AR and histone modification marks (H3K27ac, H3K4me3, H3K27me3) in 100 primary prostate carcinomas. Integrative molecular subtyping of the five data streams revealed three major subtypes of which two were clearly TMPRSS2-ERG dictated. Importantly, we identify a third subtype with low chromatin binding and activity of AR, but with high activity of FGF and WNT signaling. While positive for neuroendocrine-hallmark genes, these tumors were copy number-neutral with low mutational burden, significantly depleted for genes characteristic of poor-outcome associated luminal B-subtype. We present a unique resource on transcriptional and epigenetic control in prostate cancer, revealing tight control of gene regulation differentially dictated by AR over three subtypes.\u3c/p\u3