Nuclear envelope protein Lem2 is required for mouse development and regulates MAP and AKT kinases

The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating signaling in the nucleus. Numerous human diseases arise from mutations in lamina proteins, and experimental models for these disorders have revealed aberrant regulation of various signaling pathways. Previously, we reported that the inner nuclear membrane protein Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes, although muscle regeneration induced by cardiotoxin was delayed. By contrast, homozygous Lemd2 knockout mice died by E11.5. Although many normal morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were substantially reduced in size. This was accompanied by activation of multiple MAP kinases (ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential role in mouse embryonic development and that it is involved in regulating several signaling pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered to be another candidate gene for human disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The proteomics of quiescent and nonquiescent cell differentiation in yeast stationary-phase cultures

Starved yeast cultures differentiate into quiescent (Q) and nonquiescent (NQ) cell fractions. The yeast GFP-fusion library (4159 strains) and high-throughput flow cytometry were used to study this process. This showed significant metabolic and physiologic differences between Q/NQ cells and provided new tools for studying their differentiation

The sequence and analysis of duplication-rich human chromosome 16

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.Joel Martin, Cliff Han, Laurie A. Gordon, Astrid Terry, Shyam Prabhakar, Xinwei She, Gary Xie, Uffe Hellsten, Yee Man Chan, Michael Altherr, Olivier Couronne, Andrea Aerts, Eva Bajorek, Stacey Black, Heather Blumer, Elbert Branscomb, Nancy C. Brown, William J. Bruno, Judith M. Buckingham, David F. Callen, Connie S. Campbell, Mary L. Campbell, Evelyn W. Campbell, Chenier Caoile, Jean F. Challacombe, Leslie A. Chasteen, Olga Chertkov, Han C. Chi, Mari Christensen, Lynn M. Clark, Judith D. Cohn, Mirian Denys, John C. Detter, Mark Dickson, Mira Dimitrijevic-Bussod, Julio Escobar, Joseph J. Fawcett, Dave Flowers, Dea Fotopulos, Tijana Glavina, Maria Gomez, Eidelyn Gonzales, David Goodstein, Lynne A. Goodwin, Deborah L. Grady, Igor Grigoriev, Matthew Groza, Nancy Hammon, Trevor Hawkins, Lauren Haydu, Carl E. Hildebrand, Wayne Huang, Sanjay Israni, Jamie Jett, Phillip B. Jewett, Kristen Kadner, Heather Kimball, Arthur Kobayashi, Marie-Claude Krawczyk, Tina Leyba, Jonathan L. Longmire, Frederick Lopez, Yunian Lou, Steve Lowry, Thom Ludeman, Chitra F. Manohar, Graham A. Mark, Kimberly L. McMurray, Linda J. Meincke, Jenna Morgan, Robert K. Moyzis, Mark O. Mundt, A. Christine Munk, Richard D. Nandkeshwar, Sam Pitluck, Martin Pollard Paul Predki, Beverly Parson-Quintana, Lucia Ramirez, Sam Rash, James Retterer, Darryl O. Ricke, Donna L. Robinson, Alex Rodriguez, Asaf Salamov, Elizabeth H. Saunders, Duncan Scott, Timothy Shough, Raymond L. Stallings, Malinda Stalvey, Robert D. Sutherland, Roxanne Tapia, Judith G. Tesmer, Nina Thayer, Linda S. Thompson, Hope Tice, David C. Torney, Mary Tran-Gyamfi, Ming Tsai, Levy E. Ulanovsky, Anna Ustaszewska, Nu Vo, P. Scott White, Albert L. Williams, Patricia L. Wills, Jung-Rung Wu, Kevin Wu, Joan Yang, Pieter DeJong, David Bruce, Norman A. Doggett, Larry Deaven, Jeremy Schmutz, Jane Grimwood, Paul Richardson, Daniel S. Rokhsar, Evan E. Eichler, Paul Gilna, Susan M. Lucas, Richard M. Myers, Edward M. Rubin and Len A. Pennacchi

The sequence and analysis of duplication rich human chromosome 16

We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software