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Parkville, Australia

Li S.,New York Medical College | Labaj P.P.,University of Vienna | Zumbo P.,New York Medical College | Sykacek P.,University of Vienna | And 12 more authors.
Nature Biotechnology | Year: 2014

High-throughput RNA sequencing (RNA-seq) enables comprehensive scans of entire transcriptomes, but best practices for analyzing RNA-seq data have not been fully defined, particularly for data collected with multiple sequencing platforms or at multiple sites. Here we used standardized RNA samples with built-in controls to examine sources of error in large-scale RNA-seq studies and their impact on the detection of differentially expressed genes (DEGs). Analysis of variations in guanine-cytosine content, gene coverage, sequencing error rate and insert size allowed identification of decreased reproducibility across sites. Moreover, commonly used methods for normalization (cqn, EDASeq, RUV2, sva, PEER) varied in their ability to remove these systematic biases, depending on sample complexity and initial data quality. Normalization methods that combine data from genes across sites are strongly recommended to identify and remove site-specific effects and can substantially improve RNA-seq studies. © 2014 Nature America, Inc. Source


News Article
Site: http://www.scientificamerican.com

It can be hard to visualize how biology works at the molecular level, but biomedical animators like Drew Berry at the Walter and Eliza Hall Institute of Medical Research make it easy, using a wealth of data to create vibrant motion pictures of cellular processes in vivid color, complete with sound effects. Cells act like small cities, with proteins and other molecules moving between different factories. But they can’t move themselves. They need motor proteins to pull them or walk around. At 3:10 in this animation, you can watch two motor proteins, dynein (pale green) and kinesin (orange), strut their stuff. Animators like these integrate studies about structure, energy, and more to know just where and when to place every molecule. The hues and the sound of footsteps give them personality and bring them to life. You can watch animations on more cellular processes on WEHI’s online platforms, without needing to walk with any motor proteins to get there.


Czabotar P.E.,WEHI | Lee E.F.,WEHI | Thompson G.V.,WEHI | Wardak A.Z.,WEHI | And 4 more authors.
Journal of Biological Chemistry | Year: 2011

Pro-survival members of the Bcl-2 family of proteins restrain the pro-apoptotic activity of Bax, either directly through interactions with Bax or indirectly by sequestration of activator BH3-only proteins, or both. Mutations in Bax that promote apoptosis can provide insight into how Bax is regulated. Here, we describe crystal structures of the pro-survival proteins Mcl-1 and Bcl-xL in complex with a 34-mer peptide from Bax that encompasses its BH3 domain. These structures reveal canonical interactions between four signature hydrophobic amino acids from the BaxBH3 domain and the BH3-binding groove of the pro-survival proteins. In both structures, Met-74 from the Bax peptide engages with the BH3-binding groove in a fifth hydrophobic interaction. Various Bax Met-74 mutants disrupt interactions between Bax and all pro-survival proteins, but these Bax mutants retain pro-apoptotic activity. Bax/Bak-deficient mouse embryonic fibroblast cells reconstituted with several Bax Met-74 mutants are more sensitive to the BH3 mimetic compound ABT-737 as compared with cells expressing wild-type Bax. Furthermore, the cells expressing Bax Met-74 mutants are less viable in colony assays even in the absence of an external apoptotic stimulus. These results support a model in which direct restraint of Bax by pro-survival Bcl-2 proteins is a barrier to apoptosis. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Source

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