PO-240 Effects of aerobic exercise and fiber-enriched diet on gut microbiota in pre-diabetic patients with NAFLD: There is no full text article associated whit this abstract

  Objective Compelling evidence suggests that gut microbiota can play a role in the development of the metabolic syndrome, which incorporates abdominal obesity, hypertension, hyperglycaemia and dyslipidaemia. It is known that effective lifestyle intervention (including increasing physical exercise and calorie-restricted diet) is the mainstay treatment for the majority of patients with non-alcoholic fatty liver disease (NAFLD) and prediabetes. However, the effect of aerobic exercise and dietary intervention on gut microbiota in pre-diabetic patients with NAFLD is largely unknown and needs to be elucidated. Thus, the aim of the study was to investigate whether gut microbiota composition would change after aerobic exercise training and a fibre-enriched diet intervention in pre-diabetic patients with NAFLD. Methods We have conducted a randomized controlled trial in patients aged 50-65-year who have fulfilled the inclusion criteria (impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and hepatic fat content >5.6%, NAFLD). The patients were randomly assigned to aerobic exercise (AEx), dietary intervention (Diet), aerobic exercise plus diet intervention (AED) or no intervention (NI) groups for an average period of 8.6 months (7-11 months). Among those participants, 78 provided fecal samples (AEx, n = 18, Diet, n = 22, AED = 21, and NI = 17). Progressive supervised aerobic exercise training (60-75% intensity) was given 2-3 times/week in 30-60 min/sessions, and the diet intervention was provided as lunch with 38% carbohydrate and diet fibre of 12g per day for 8.6-months. The hepatic fat content (HFC) was assessed by 1H MRS, glycated hemoglobin (HbA1c) and insulin sensitivity were assessed by conventional methods. Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing by Illumina Miseq platform. Results The Simpson index showed that alpha diversity was significantly different in intervention groups compared with NI group after the intervention (AEx vs NI, p=0.070; Diet vs NI, p=0.014; AED vs NI, p=0.011). Simpson index had a negative trend with HFC change % after intervention (r=-0.254, p=0.053). Weighted UniFrac PCoA analysis revealed that the structure of gut microbiota in the intervention groups was significantly differed from that of NI group (AEx vs NI, p<0.01, Diet vs NI, p<0.05, AED vs NI, p<0.001). Interestingly, we found that Erysipelotrichi (which has been reported associated with NASH) was negatively correlated VO2max (r=-0.274, p=0.040). At genus level, Clostridium and Lactobacillus were positively correlated with HFC change after intervention (r=0.273, p=0.038; r=0.273, p=0.041 respectively). Conclusions The exercise and diet intervention modified the structure of gut microbiota both in alpha and beta diversity. The Clostridium and Lactobacillus is related to energy metabolism and participated in the fermentation of carbohydrate which may be partly explain the positive correlation of gut microbiota with HFC change. However, the function of specific gut microbe needs to be further studied. &nbsp

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Triplex Blue-shifting Hydrogen Bonds of ClO₄^–···H–C in the Nanointerlayer of Montmorillonite Complexed with Cetyltrimethylammonium Cation from Hydrophilic to Hydrophobic Properties

In this study, molecular interactions of perchlorate (ClO₄^–), an emerging pollutant, with cetyltrimethylammonium­(CTMA⁺) complexed in the nanointerlayer of negatively charged montmorillonite were characterized using the zeta potentials, FTIR, Raman, and XRD spectroscopy and quantified using quantum mechanical calculations and sorption experiments. We found that blue-shifting hydrogen bonds assisted in the uptake of ClO₄^– from water into the nanointerlayer spacing of CTMA⁺-montmorillonite and were tunable according to CTMA⁺ loading. FTIR spectra presented an obvious 47 cm^–1 blue shift in the C–H vibration coming from the N-terminal methyl group of CTMA⁺ when ClO₄^– was absorbed. Quantum mechanical calculations based on density functional theory demonstrated that triplex blue-shifting hydrogen bonds of C–H···O were formed between the three terminal methyl groups of CTMA⁺ and three oxygen atoms of ClO₄^–. The contribution of blue-shifting hydrogen bonds to perchlorate uptake switched from a ClO₄^–/CTMA⁺ ratio of 0.0453 at low CTMA⁺ loadings to a ClO₄^–/CTMA⁺ ratio of 0.2563 (5.6-fold) at high CTMA⁺ loadings, which can be ascribed to the evolution of the nanointerlayer microenvironments from hydrophilic properties to hydrophobic properties. The blue-shifting hydrogen bond of C–H···O that is tunable with the hydrophobic nature of the organic phase should be recognized to elucidate the biochemical behavior of perchlorate in organisms

Atomic Insights into Distinct Hormonal Activities of Bisphenol A Analogues toward PPARγ and ERα Receptors

Bisphenol A analogues (BPAs) belong to a wide variety of large volume chemicals with diverse applications yet emerging environmental concerns. Limited experimental data have demonstrated that BPAs with different halogenation patterns distinctly affect the agonistic activities toward proliferator-activated receptor (PPAR)­γ and estrogen receptors (ER)­α. Understanding the modes of action of BPAs toward different receptors is essential, however, the underlying molecular mechanism is still poorly understood. Here we probed the molecular recognition process of halogenated BPAs including TBBPA, TCBPA, BPAF, BPC, triBBPA, diBBPA, and monoBBPA toward PPARγ and ERα by molecular modeling, especially the impact of different halogen patterns. Increasing bromination at phenolic rings of BPAs was found highly correlated with electrostatic interactions (<i>R</i>² = 0.978 and 0.865 toward PPARγ and ERα, respectively) and van der Waals interactions (<i>R</i>² = 0.995 and 0.994 toward PPARγ and ERα, respectively). More halogenated phenolic rings at 3,5-positions of BPAs increase the shielding of the hormonally active phenolic OH and markedly decrease electrostatic interactions favorable for agonistic activities toward PPARγ, but unfavorable for agonistic activities toward ERα. The halogenation at the phenolic rings of BPAs exerts more impact on molecular electrostatic potential distribution than halogenation at the bridging alkyl moiety. Different halogenations further alter hydrogen bond interactions of BPAs and induce conformational changes of PPARγ ligand binding domain (LBD) and ERα LBD, specifically affecting the stabilization of helix H12 attributable to the different agonistic activities. Our results indicate that structural variations in halogenation patterns result in different interactions of BPAs with PPARγ LBD and ERα LBD, potentially causing distinct agonistic/antagonistic toxic effects. The various halogenation patterns should be fully considered for the design of future environmentally benign chemicals with reduced toxicities and desired properties

Low concentrations of o,p'-DDT inhibit gene expression and prostaglandin synthesis by estrogen receptor-independent mechanism in rat ovarian cells.

o,p'-DDT is an infamous xenoestrogen as well as a ubiquitous and persistent pollutant. Biomonitoring studies show that women have been internally exposed to o,p'-DDT at range of 0.3-500 ng/g (8.46×10(-10) M-1.41×10(-6) M) in blood and other tissues. However, very limited studies have investigated the biological effects and mechanism(s) of o,p'-DDT at levels equal to or lower than current exposure levels in human. In this study, using primary cultures of rat ovarian granulosa cells, we determined that very low doses of o,p'-DDT (10(-12)-10(-8) M) suppressed the expression of ovarian genes and production of prostaglandin E2 (PGE2). In vivo experiments consistently demonstrated that o,p'-DDT at 0.5-1 mg/kg inhibited the gene expression and PGE2 levels in rat ovary. The surprising results from the receptor inhibitors studies showed that these inhibitory effects were exerted independently of either classical estrogen receptors (ERs) or G protein-coupled receptor 30 (GPR30). Instead, o,p'-DDT altered gene expression or hormone action via inhibiting the activation of protein kinase A (PKA), rather than protein kinase C (PKC). We further revealed that o,p'-DDT directly interfered with the PKA catalytic subunit. Our novel findings support the hypothesis that exposure to low concentrations of o,p'-DDT alters gene expression and hormone synthesis through signaling mediators beyond receptor binding, and imply that the current exposure levels of o,p'-DDT observed in the population likely poses a health risk to female reproduction