262 research outputs found

    MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

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    Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe

    Modulation of microglia by Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model

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    The active component of Wolfberry (Lycium barbarum), lycium barbarum polysaccharides (LBP), has been shown to be neuroprotective to retinal ganglion cells (RGCs) against ocular hypertension (OH). Aiming to study whether this neuroprotection is mediated via modulating immune cells in the retina, we used multiphoton confocal microscopy to investigate morphological changes of microglia in whole-mounted retinas. Retinas under OH displayed slightly activated microglia. One to 100 mg/kg LBP exerted the best neuroprotection and elicited moderately activated microglia in the inner retina with ramified appearance but thicker and focally enlarged processes. Intravitreous injection of lipopolysaccharide decreased the survival of RGCs at 4 weeks, and the activated microglia exhibited amoeboid appearance as fully activated phenotype. When activation of microglia was attenuated by intravitreous injection of macrophage/microglia inhibitory factor, protective effect of 10 mg/kg LBP was attenuated. The results implicated that neuroprotective effects of LBP were partly due to modulating the activation of microglia

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    1)発育状態は,強化酵母を添加した飼料によるものがすぐれていた。2)強化酵母無添加の飼料によるものは,雄1匹,雌2匹が死亡した,これは感染する病気が原因と思われる。3)強化酵母無添加の飼料によるものは,いずれも妊娠しなかったが,添加したものは3匹が各々妊娠し出産した。これにより,強化酵母が繁殖に効果があると思われる。なお,今回の実験が夏期であったので,さらに季節をかえて実験を重ねたいと思う

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    (1)加熱時間別の浸透状態を見ると,外層ではおよそ30分間の浸透が著しくその後の変化は少ない。内層に食塩が浸透しはじめるのは,沸騰後約20分で,その後20分間に浸透が進んだ。 (2)食塩添加の時機による差は,食塩添加後の加熱時間が同じ場合は,じゃがいもが煮えた状態で添加したものの浸透状態がよかった。また,煮えてから添加しても,添加後の加熱時間が短かければ浸透は少ない。 (3)加熱後の食塩の移動状態をみると,室温放置の場合は,外層から内層への移動状態がはっきりとみられ,外層と内層の食塩濃度の差は時間の経過とともに少なくなった。煮汁に浸しておいたものでは,食塩水からの浸透が続くため,時間が経過しても外層と内層との差はほとんど変らなかった。外層・内層とも2時間までにほぼ浸透し,その後はあまり浸透しなかった。従って加熱後2時間までの浸透状態を今後検討したい

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    (1)発育状態はよもぎ粉末を添加した場合,0.3~0.5%程度の微量では効果が少ない。(2)添加量を増すことにより,成長に効果があり,3~10%までにおいては添加の量の多いほど体重の増加は良好である。(3)あくをぬかない飼料によるものは,あくぬきのものに比べて体重の増加は極めて悪い。(4)解剖の結果において,内臓に異状はなかった。本実験において以上のことがわかったがなお,よもぎ粉末を10%以上添加して飼育した場合,およびよもぎのあくぬき方,成分等について今後研究を重ねたいと思う
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