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The birds of Genome10K

OBrien, Stephen J Haussler, David Ryder, Oliver

Published in GigaScience

Everyone loves the birds of the world. From their haunting songs and majesty of flight to dazzling plumage and mating rituals, bird watchers – both amateurs and professionals - have marveled for centuries at their considerable adaptations. Now, we are offered a special treat with the publication of a series of papers in dedicated issues of Science,...

Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA

Deng, Nan Jiao, Yan Cao, Yanhong Liu, Xiaoyun Ma, Yonghui Hasty, Karen A Brand, David D Stuart, John M Gu, Weikuan

Published in BMC Immunology

BackgroundTo understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1−/− mice that are resistant to spontaneous arthritis into BALB/c−/− mice which are susceptible....

PKC inhibition results in a Kv 1.5 + Kv β1.3 pharmacology closer to Kv 1.5 channels.

Macías, A de la Cruz, A Prieto, A Peraza, D A Tamkun, M M González, T Valenzuela, C

Published in British journal of pharmacology

The finding that the voltage-dependence of inactivation and the pharmacology of Kv 1.5 + Kv β1.3 channels after PKC inhibition resembled that observed in Kv 1.5 channels suggests that both processes are dependent on PKC-mediated phosphorylation. These results may have clinical relevance in diseases that are characterized by alterations in kinase ac...

Transcriptional regulation by trithorax-group proteins.

Kingston, Robert E Tamkun, John W

Published in Cold Spring Harbor perspectives in biology

The trithorax group of genes (trxG) was identified in mutational screens that examined developmental phenotypes and suppression of Polycomb mutant phenotypes. The protein products of these genes are primarily involved in gene activation, although some can also have repressive effects. There is no central function for these proteins. Some move nucle...

Gene repression. H3K27me and PRC2 transmit a memory of repression across generations and during development.

Gaydos, Laura J Wang, Wenchao Strome, Susan

Published in Science (New York, N.Y.)

For proper development, cells must retain patterns of gene expression and repression through cell division. Repression via methylation of histone H3 on Lys27 (H3K27me) by Polycomb repressive complex 2 (PRC2) is conserved, but its transmission is not well understood. Our studies suggest that PRC2 represses the X chromosomes in Caenorhabditis elegans...

Luminal cells are favored as the cell of origin for prostate cancer.

Wang, Zhu A Toivanen, Roxanne Bergren, Sarah K Chambon, Pierre Shen, Michael M

Published in Cell reports

The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. ...

SLIT/ROBO2 signaling promotes mammary stem cell senescence by inhibiting Wnt signaling.

Harburg, Gwyndolen Compton, Jennifer Liu, Wei Iwai, Naomi Zada, Shahrzad Marlow, Rebecca Strickland, Phyllis Zeng, Yi Arial Hinck, Lindsay

Published in Stem cell reports

WNT signaling stimulates the self-renewal of many types of adult stem cells, including mammary stem cells (MaSCs), but mechanisms that limit this activity are poorly understood. Here, we demonstrate that SLIT2 restricts stem cell renewal by signaling through ROBO2 in a subset of basal cells to negatively regulate WNT signaling. The absence of SLIT/...

Comparative analysis of metazoan chromatin organization.

Ho, Joshua W K Jung, Youngsook L Liu, Tao Alver, Burak H Lee, Soohyun Ikegami, Kohta Sohn, Kyung-Ah Minoda, Aki Tolstorukov, Michael Y Appert, Alex ...

Published in Nature

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation...

Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells.

Flach, Johanna Bakker, Sietske T Mohrin, Mary Conroy, Pauline C Pietras, Eric M Reynaud, Damien Alvarez, Silvia Diolaiti, Morgan E Ugarte, Fernando Forsberg, E Camilla ...

Published in Nature

Haematopoietic stem cells (HSCs) self-renew for life, thereby making them one of the few blood cells that truly age. Paradoxically, although HSCs numerically expand with age, their functional activity declines over time, resulting in degraded blood production and impaired engraftment following transplantation. While many drivers of HSC ageing have ...

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

Hoadley, Katherine A Yau, Christina Wolf, Denise M Cherniack, Andrew D Tamborero, David Ng, Sam Leiserson, Max D M Niu, Beifang McLellan, Michael D Uzunangelov, Vladislav ...

Published in Cell

Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a u...

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