Day-Time Patterns of Carbohydrate Intake in Adults by Non-Parametric Multi-Level Latent Class Analysis-Results from the UK National Diet and Nutrition Survey (2008/09-2015/16).

This study aims at combining time and quantity of carbohydrate (CH) intake in the definition of eating patterns in UK adults and investigating the association of the derived patterns with type 2 diabetes (T2D). The National Diet and Nutrition Survey (NDNS) Rolling Program included 6155 adults in the UK. Time of the day was categorized into 7 pre-defined time slots: 6-9 am, 9-12 noon, 12-2 pm, 2-5 pm, 5-8 pm, 8-10 pm, and 10 pm-6 am. Responses for CH intake were categorized into: no energy intake, CH <50% or ≥50% of total energy. Non-parametric multilevel latent class analysis (MLCA) was applied to identify eating patterns of CH consumption across day-time, as a novel method accounting for the repeated measurements of intake over 3-4 days nested within individuals. Survey-designed multivariable regression was used to assess the associations of CH eating patterns with T2D. Three CH eating day patterns (low, high CH percentage and frequent CH intake day) emerged from 24,483 observation days; based on which three classes of CH eaters were identified and characterized as: low (28.1%), moderate (28.8%) and high (43.1%) CH eaters. On average, low-CH eaters consumed the highest amount of total energy intake (7985.8 kJ) and had higher percentages of energy contributed by fat and alcohol, especially after 8 pm. Moderate-CH eaters consumed the lowest amount of total energy (7341.8 kJ) while they tended to have their meals later in the day. High-CH eaters consumed most of their carbohydrates and energy earlier in the day and within the time slots of 6-9 am, 12-2 pm and 5-8 pm, which correspond to traditional mealtimes. The high-CH eaters profile had the highest daily intake of CH and fiber and the lowest intake of protein and fat. Low-CH eaters had greater odds than high-CH eaters of having T2D in self-reported but not in previously undiagnosed diabetics. Further research using prospective longitudinal studies is warranted to ascertain the direction of causality in the association of CH patterns with type 2 diabetes

PEG10 directly regulated by E2Fs might have a role in the development of hepatocellular carcinoma

AbstractPEG10 is an imprinted gene which is up-regulated in hepatocelluar carcinoma (HCC). However, the mechanism of PEG10 regulation remains to be elucidated. In this work the transcription factors E2F-1 and -4 were demonstrated to bind directly to the promoter of PEG10 and thereby regulate its expression. The expression profile of HCC tissues also suggested E2Fs were involved in PEG10 regulation. Further functional analysis showed that PEG10 was involved in the repression of apoptosis induced by serum deprivation and chemotherapeutic drugs. These findings link cancer genetics and epigenetics by showing that E2F acts directly upstream of an anti-apoptosis imprinted gene, PEG10

Identification of H3K4me1-associated proteins at mammalian enhancers.

Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators

The complex hexaploid oil‐Camellia genome traces back its phylogenomic history and multi‐omics analysis of Camellia oil biosynthesis

Summary: Oil‐Camellia (Camellia oleifera), belonging to the Theaceae family Camellia, is an important woody edible oil tree species. The Camellia oil in its mature seed kernels, mainly consists of more than 90% unsaturated fatty acids, tea polyphenols, flavonoids, squalene and other active substances, which is one of the best quality edible vegetable oils in the world. However, genetic research and molecular breeding on oil‐Camellia are challenging due to its complex genetic background. Here, we successfully report a chromosome‐scale genome assembly for a hexaploid oil‐Camellia cultivar Changlin40. This assembly contains 8.80 Gb genomic sequences with scaffold N50 of 180.0 Mb and 45 pseudochromosomes comprising 15 homologous groups with three members each, which contain 135 868 genes with an average length of 3936 bp. Referring to the diploid genome, intragenomic and intergenomic comparisons of synteny indicate homologous chromosomal similarity and changes. Moreover, comparative and evolutionary analyses reveal three rounds of whole‐genome duplication (WGD) events, as well as the possible diversification of hexaploid Changlin40 with diploid occurred approximately 9.06 million years ago (MYA). Furthermore, through the combination of genomics, transcriptomics and metabolomics approaches, a complex regulatory network was constructed and allows to identify potential key structural genes (SAD, FAD2 and FAD3) and transcription factors (AP2 and C2H2) that regulate the metabolism of Camellia oil, especially for unsaturated fatty acids biosynthesis. Overall, the genomic resource generated from this study has great potential to accelerate the research for the molecular biology and genetic improvement of hexaploid oil‐Camellia, as well as to understand polyploid genome evolution

An epigenetic switch induced by Shh signalling regulates gene activation during development and medulloblastoma growth

The Sonic hedgehog (Shh) signalling pathway plays important roles during development and in cancer. Here we report a Shh-induced epigenetic switch that cooperates with Gli to control transcription outcomes. Before induction, poised Shh target genes are marked by a bivalent chromatin domain containing a repressive histone H3K27me3 mark and an active H3K4me3 mark. Shh activation induces a local switch of epigenetic cofactors from the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) to an H3K27me3 demethylase Jmjd3/Kdm6b-centred coactivator complex. We also find that non-enzymatic activities of Jmjd3 are important and that Jmjd3 recruits the Set1/MLL H3K4 methyltransferase complexes in a Shh-dependent manner to resolve the bivalent domain. In vivo, changes of the bivalent domain accompanied Shh-activated cerebellar progenitor proliferation. Overall, our results reveal a regulatory mechanism that underlies the activation of Shh target genes and provides insight into the causes of various diseases and cancers exhibiting altered Shh signalling

A Complete Axiom System for Propositional Interval Temporal Logic with Infinite Time

Interval Temporal Logic (ITL) is an established temporal formalism for reasoning about time periods. For over 25 years, it has been applied in a number of ways and several ITL variants, axiom systems and tools have been investigated. We solve the longstanding open problem of finding a complete axiom system for basic quantifier-free propositional ITL (PITL) with infinite time for analysing nonterminating computational systems. Our completeness proof uses a reduction to completeness for PITL with finite time and conventional propositional linear-time temporal logic. Unlike completeness proofs of equally expressive logics with nonelementary computational complexity, our semantic approach does not use tableaux, subformula closures or explicit deductions involving encodings of omega automata and nontrivial techniques for complementing them. We believe that our result also provides evidence of the naturalness of interval-based reasoning

Hybrid Relations in Isabelle/UTP

We describe our UTP theory of hybrid relations, which extends the relational calculus with continuous variables and differential equations. This enables the use of UTP in modelling and verification of hybrid systems, supported by our mechanisation in Isabelle/UTP. The hybrid relational calculus is built upon the same foundation as the UTP’s theory of reactive processes, which is accomplished through a generalised trace algebra and a model of piecewise-continuous functions. From this foundation, we give semantics to hybrid programs, including ordinary differential equations and preemption, and show how the theory can be used to reason about sequential hybrid systems

Roadmap for the development of the University of North Carolina at Chapel Hill Genitourinary OncoLogy Database—UNC GOLD

The management of genitourinary malignancies requires a multidisciplinary care team composed of urologists, medical oncologists and radiation oncologists. A genitourinary (GU) oncology clinical database is an invaluable resource for patient care and research. Although electronic medical records provide a single web-based record used for clinical care, billing and scheduling, information is typically stored in a discipline-specific manner and data extraction is often not applicable to a research setting. A GU oncology database may be used for the development of multidisciplinary treatment plans, analysis of disease-specific practice patterns, and identification of patients for research studies. Despite the potential utility, there are many important considerations that must be addressed when developing and implementing a discipline-specific database