290 research outputs found
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
Revolutionizing Drug Discovery: The Impact of Distinct Designs and Biosensor Integration in Microfluidics-Based Organ-on-a-Chip Technology
Traditional drug development is a long and expensive process with high rates of failure. This has prompted the pharmaceutical industry to seek more efficient drug development frameworks, driving the emergence of organ-on-a-chip (OOC) based on microfluidic technologies. Unlike traditional animal experiments, OOC systems provide a more accurate simulation of human organ microenvironments and physiological responses, therefore offering a cost-effective and efficient platform for biomedical research, particularly in the development of new medicines. Additionally, OOC systems enable quick and real-time analysis, high-throughput experimentation, and automation. These advantages have shown significant promise in enhancing the drug development process. The success of an OOC system hinges on the integration of specific designs, manufacturing techniques, and biosensors to meet the need for integrated multiparameter datasets. This review focuses on the manufacturing, design, sensing systems, and applications of OOC systems, highlighting their design and sensing capabilities, as well as the technical challenges they currently face
Application of Prestressing Technology in Ultra-large LNG Storage Tanks at the "Green Energy Port" Project in Yancheng, Jiangsu Province
The Yancheng "Green Energy Port" is an important project planned under the National Natural Gas Production, Supply, Storage, and Sales System Construction and Interconnectivity program, and it is also the largest liquefied natural gas (LNG) reserve base currently under construction in China. In the first phase of the "Green Energy Port" project, 10 large LNG storage tanks were built, including 4 tanks with a capacity of 220,000 m3 and 6 tanks with a capacity of 270,000 m3 , the latter of which are currently the largest storage tanks with a single-tank capacity in the world. This report provides a brief introduction to the project context, outlines the layout of the prestressed system in the LNG storage tanks and the construction phases, and summarizes the critical tests for the prestress system in cryogenic tanks
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
MatrixGate: A High-performance Data Ingestion Tool for Time-series Databases
Recent years have seen massive time-series data generated in many areas. This
different scenario brings new challenges, particularly in terms of data
ingestion, where existing technologies struggle to handle such massive
time-series data, leading to low loading speed and poor timeliness. To address
these challenges, this paper presents MatrixGate, a new and efficient data
ingestion approach for massive time-series data. MatrixGate implements both
single-instance and multi-instance parallel procedures, which is based on its
unique ingestion strategies. First, MatrixGate uses policies to tune the slots
that are synchronized with segments to ingest data, which eliminates the cost
of starting transactions and enhance the efficiency. Second, multi-coroutines
are responsible for transfer data, which can increase the degree of parallelism
significantly. Third, lock-free queues are used to enable direct data transfer
without the need for disk storage or lodging in the master instance. Experiment
results on multiple datasets show that MatrixGate outperforms state-of-the-art
methods by 3 to 100 times in loading speed, and cuts down about 80% query
latency. Furthermore, MatrixGate scales out efficiently under distributed
architecture, achieving scalability of 86%
Prevalence and predictors of prediabetes and diabetes among adults in Palau : population-based national STEPS survey
2016-11We aimed to investigate the prevalence and predictors of diabetes and prediabetes among adults in Palau. We used data of 1915 adults, aged 25 to 64 years, who participated in the World Health Organization’s (WHO) STEPwise Approach to Risk Factor Surveillance (STEPS) study in Palau. Information on behavioral risk factors of NCDs and physical and biochemical measurements were obtained using standard methods of the WHO. The diagnosis of diabetes and prediabetes was based on the recent American Diabetes Association criteria. Predictors of the prevalence of diabetes and prediabetes were identified using multinomial logistic regression analysis. The overall age-standardized prevalence of prediabetes and diabetes were 40.4% (43.6% for men, 37.4% for women) and 17.7% (18.6% for men, 17% for women), respectively. Old age, overall obesity (high BMI), central obesity (large waist circumference or waist-hip ratio), hypertension and hypertriglyceridemia were significant predictors of prediabetes and/or diabetes. Diabetes occurred at a younger age in “obese” individuals than that of their “non-obese” counterparts. We confirmed that prediabetes and diabetes are highly prevalent in Palau affecting 40% and 18% adults, respectively. Introducing public health interventions to reduce and prevent obesity as early as possible could prove useful to curb the problem.departmental bulletin pape
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
Author response: H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation
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