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Multistart simulated annealing refinement of the crystal structure of the 70S ribosome.

Korostelev, Andrei Laurberg, Martin Noller, Harry F

Published in Proceedings of the National Academy of Sciences of the United States of America

A macromolecular X-ray crystal structure is usually represented as a single static model with a single set of temperature factors representing a simple approximation of motion and disorder of the structure. Multiconformer representations of small proteins have been shown to better describe anisotropic motion and disorder and improve the quality of ...

The infinite sites model of genome evolution.

Ma, Jian Ratan, Aakrosh Raney, Brian J Suh, Bernard B Miller, Webb Haussler, David

Published in Proceedings of the National Academy of Sciences of the United States of America

We formalize the problem of recovering the evolutionary history of a set of genomes that are related to an unseen common ancestor genome by operations of speciation, deletion, insertion, duplication, and rearrangement of segments of bases. The problem is examined in the limit as the number of bases in each genome goes to infinity. In this limit, th...

Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass.

Smoum, Reem Bar, Arik Tan, Bo Milman, Garry Attar-Namdar, Malka Ofek, Orr Stuart, Jordyn M Bajayo, Alon Tam, Joseph Kram, Vardit ...

Published in Proceedings of the National Academy of Sciences of the United States of America

Bone mass is determined by a continuous remodeling process, whereby the mineralized matrix is being removed by osteoclasts and subsequently replaced with newly formed bone tissue produced by osteoblasts. Here we report the presence of endogenous amides of long-chain fatty acids with amino acids or with ethanolamine (N-acyl amides) in mouse bone. Of...

Demographic history and rare allele sharing among human populations.

Gravel, Simon Henn, Brenna M Gutenkunst, Ryan N Indap, Amit R Marth, Gabor T Clark, Andrew G Yu, Fuli Gibbs, Richard A Bustamante, Carlos D

Published in Proceedings of the National Academy of Sciences of the United States of America

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to da...

Targeting protein-trafficking pathways alters melanoma treatment sensitivity.

Huang, Zhi-ming Chinen, Milka Chang, Philip J Xie, Tong Zhong, Lily Demetriou, Stephanie Patel, Mira P Scherzer, Rebecca Sviderskaya, Elena V Bennett, Dorothy C ...

Published in Proceedings of the National Academy of Sciences of the United States of America

Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide to...

Transoceanic drift and the domestication of African bottle gourds in the Americas.

Kistler, Logan Montenegro, Alvaro Smith, Bruce D Gifford, John A Green, Richard E Newsom, Lee A Shapiro, Beth

Published in Proceedings of the National Academy of Sciences of the United States of America

Bottle gourd (Lagenaria siceraria) was one of the first domesticated plants, and the only one with a global distribution during pre-Columbian times. Although native to Africa, bottle gourd was in use by humans in east Asia, possibly as early as 11,000 y ago (BP) and in the Americas by 10,000 BP. Despite its utilitarian importance to diverse human p...

Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system.

Jiao, Jian-Wei Feldheim, David A Chen, Dong Feng

Published in Proceedings of the National Academy of Sciences of the United States of America

In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report th...

Multiplex protein assays based on real-time magnetic nanotag sensing.

Osterfeld, Sebastian J Yu, Heng Gaster, Richard S Caramuta, Stefano Xu, Liang Han, Shu-Jen Hall, Drew A Wilson, Robert J Sun, Shouheng White, Robert L ...

Published in Proceedings of the National Academy of Sciences of the United States of America

Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly so...

Early doors (Edo) mutant mouse reveals the importance of period 2 (PER2) PAS domain structure for circadian pacemaking.

Militi, Stefania Maywood, Elizabeth S Sandate, Colby R Chesham, Johanna E Barnard, Alun R Parsons, Michael J Vibert, Jennifer L Joynson, Greg M Partch, Carrie L Hastings, Michael H ...

Published in Proceedings of the National Academy of Sciences of the United States of America

The suprachiasmatic nucleus (SCN) defines 24 h of time via a transcriptional/posttranslational feedback loop in which transactivation of Per (period) and Cry (cryptochrome) genes by BMAL1-CLOCK complexes is suppressed by PER-CRY complexes. The molecular/structural basis of how circadian protein complexes function is poorly understood. We describe a...

Rotation of the head of the 30S ribosomal subunit during mRNA translocation.

Guo, Zhuojun Noller, Harry F

Published in Proceedings of the National Academy of Sciences of the United States of America

Elongation factor-G-catalyzed translocation of mRNA and tRNAs during protein synthesis involves large-scale conformational changes in the ribosome. Formation of hybrid-state intermediates is coupled to counterclockwise (forward) rotation of the body of the 30S subunit. Recent structural studies implicate intrasubunit rotation of the 30S head in tra...

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