25 research outputs found
The Linked Data Benchmark Council (LDBC): Driving competition and collaboration in the graph data management space
Graph data management is instrumental for several use cases
such as recommendation, root cause analysis, financial fraud detection,
and enterprise knowledge representation. Efficiently supporting these use
cases yields a number of unique requirements, including the need for a
concise query language and graph-aware query optimization techniques.
The goal of the Linked Data Benchmark Council (LDBC) is to design
a set of standard benchmarks that capture representative categories of
graph data management problems, making the performance of systems
comparable and facilitating competition among vendors. LDBC also
conducts research on graph schemas and graph query languages. This
paper introduces the LDBC organization and its work over the last decade
ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation.
Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodelling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify epithelial splicing regulatory protein 2 (ESRP2) as a conserved regulatory factor that controls the neonatal-to-adult switch of ∼20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing and causes various physiological abnormalities. These findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate terminal differentiation and maturation of hepatocytes
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ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation.
Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodelling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify epithelial splicing regulatory protein 2 (ESRP2) as a conserved regulatory factor that controls the neonatal-to-adult switch of ∼20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing and causes various physiological abnormalities. These findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate terminal differentiation and maturation of hepatocytes
Characterization of the RNA recognition mode of hnRNP G extends its role in SMN2 splicing regulation
Regulation of SMN2 exon 7 splicing is crucial for the production of active SMN protein and the survival of Spinal Muscular Atrophy (SMA) patients. One of the most efficient activators of exon 7 inclusion is hnRNP G, which is recruited to the exon by Tra2-β1. We report that in addition to the C-terminal region of hnRNP G, the RNA Recognition Motif (RRM) and the middle part of the protein containing the Arg–Gly–Gly (RGG) box are important for this function. To better understand the mode of action of hnRNP G in this context we determined the structure of its RRM bound to an SMN2 derived RNA. The RRM interacts with a 5′-AAN-3′ motif and specifically recognizes the two consecutive adenines. By testing the effect of mutations in hnRNP G RRM and in its putative binding sites on the splicing of SMN2 exon 7, we show that it specifically binds to exon 7. This interaction is required for hnRNP G splicing activity and we propose its recruitment to a polyA tract located upstream of the Tra2-β1 binding site. Finally, our data suggest that hnRNP G plays a major role in the recruitment of the Tra2-β1/hnRNP G/SRSF9 trimeric complex to SMN2 exon 7
Benefits Of Communications Infrastructure Capital In U.S. Economy
In this paper we empirically estimate the contribution of the communications infrastructure to the growth of output and productivity at the dis-aggregate industry and at the aggregate economy levels. The estimated value of the marginal benefits or the shadow price of the communications infrastructure capital is positive in each of 34 industries representing the major industrial sectors of the U.S. economy. This effect captures network externality benefits and can be interpreted as a willingness to pay by each industry for communications infrastructure capital services over and above their direct payments for communications services. These results suggest that an increase in communications infrastructure capital services reduces cost in all the industries and as a consequence that of the entire economy. The relatively high value of estimated total marginal benefits for the aggregate economy indicates a high social rate of return to the investments in communications infrastructure.communications, infrastructure, network externality, marginal benefits, productivity, JEL Code D2; D24; LOO; L86; L96; 047,
The linked data benchmark council (LDBC): Driving competition and collaboration in the graph data management space
Graph data management is instrumental for several use cases
such as recommendation, root cause analysis, financial fraud detection,
and enterprise knowledge representation. Efficiently supporting these use
cases yields a number of unique requirements, including the need for a
concise query language and graph-aware query optimization techniques.
The goal of the Linked Data Benchmark Council (LDBC) is to design
a set of standard benchmarks that capture representative categories of
graph data management problems, making the performance of systems
comparable and facilitating competition among vendors. LDBC also
conducts research on graph schemas and graph query languages. This
paper introduces the LDBC organization and its work over the last decad