5,766 research outputs found

    Network rewiring is an important mechanism of gene essentiality change.

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    Gene essentiality changes are crucial for organismal evolution. However, it is unclear how essentiality of orthologs varies across species. We investigated the underlying mechanism of gene essentiality changes between yeast and mouse based on the framework of network evolution and comparative genomic analysis. We found that yeast nonessential genes become essential in mouse when their network connections rapidly increase through engagement in protein complexes. The increased interactions allowed the previously nonessential genes to become members of vital pathways. By accounting for changes in gene essentiality, we firmly reestablished the centrality-lethality rule, which proposed the relationship of essential genes and network hubs. Furthermore, we discovered that the number of connections associated with essential and non-essential genes depends on whether they were essential in ancestral species. Our study describes for the first time how network evolution occurs to change gene essentiality

    Rampant exchange of the structure and function of extramembrane domains between membrane and water soluble proteins.

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    Of the membrane proteins of known structure, we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure. Moreover, 41% of known water soluble protein structures share a domain with an already known membrane protein structure. We also found that functional residues are frequently conserved between extramembrane domains of membrane and soluble proteins that share structural similarity. These results suggest membrane and soluble proteins readily exchange domains and their attendant functionalities. The exchanges between membrane and soluble proteins are particularly frequent in eukaryotes, indicating that this is an important mechanism for increasing functional complexity. The high level of structural overlap between the two classes of proteins provides an opportunity to employ the extensive information on soluble proteins to illuminate membrane protein structure and function, for which much less is known. To this end, we employed structure guided sequence alignment to elucidate the functions of membrane proteins in the human genome. Our results bridge the gap of fold space between membrane and water soluble proteins and provide a resource for the prediction of membrane protein function. A database of predicted structural and functional relationships for proteins in the human genome is provided at sbi.postech.ac.kr/emdmp

    The cytochemical localization of adenyl cyclase activity in rat sublingual gland

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    Adenyl cyclase activity in mucous acinar cells and serous demilune cells of the rat sublingual gland was localized cytochemically. After incubation with adenylyl-imidodiphosphate (AMP-PNP) as substrate, deposits of reaction product are found along the cell membranes bordering the secretory surfaces of serous demilune cells. These are the membranes which participate directly in secretion by fusing with the granule membranes. The granule membranes of the demilune cells do not reveal reaction product, but the membranes of the granules which are fused with and become part of the cell membrane do show deposits. Thus, it appears that the cell membranes which fuse with granule membranes during secretion are associated with a high level of adenyl cyclase activity. In support of this, the luminal membranes of the mucous acinar cells which do not fuse with granule membranes during secretion are not associated with detectable amounts of adenyl cyclase activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49675/1/1001440407_ftp.pd

    Decision Supporting Methodology and System Based on Theory of Constraints for Making an Optimal Product Portfolio Strategy in Shipbuilding Industry

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    Shipbuilding is a typical ‘build to order’ industry. It has a business model that generates revenues from building various ships and offshore products in accordance with owner’s requirements at each production stage. Under uncertainty in shipping market, it is very essential for the shipbuilder to prepare the fast and competitive decision for product portfolio strategy in order to maximize contribution margin by exploiting production facilities and constraints. TOC(theory of constrains) proposed by Dr. goldratt in 1979 has been evolved into a management philosophy with practices and principles spanning a multitude of operations management sub-disciplines.[1] In this study, we introduce the unique decision supporting methodology for the optimal product portfolio sets based on TOC. This methodology is established by adopting the concept of Drum Buffer Rope (DBR)[2] in constraints planning and Throughput Account (TA)[3][4][5] in management accounting of TOC. In addition, Decision Supporting System (DSS)[6] is implemented by applying this methodology. This DSS system provides a throughput estimator with reflecting the cost structure of shipbuilding industry and a resource simulator built on heuristic algorithms to operate major constraint-resources in shipyard such as dock, quay and pre-erection area etc. Several examples are presented to show that the proposed methodology and system can effectively support the strategic decision-making process of a global shipbuilding company
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