Mapping and analysis of chromatin state dynamics in nine human cell types

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.     

Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.     

Identity of the proliferating cell nuclear antigen and cyclin

Studies of growth regulation and cellular transformation will be assisted by the identification of proteins that are preferentially synthesized in dividing cells. The 'proliferating cell nuclear antigen' ( PCNA ), distinguished by its apparent association with cell division, is defined by reaction with an antibody found in the autoimmune disease systemic lupus erythematosus (SLE). This antibody reacts with proliferating cells including tumour cells but gives weak or undetectable immunofluorescence with resting cells of normal tissues. Peripheral blood lymphocytes are devoid of PCNA until activated by mitogen in vitro. In synchronized cultures its level and distribution fluctuate through the cell cycle, with a striking accumulation in the nucleolus late in the G1 phase and early in the S phase. Many of these properties are shared by ' cyclin '. This nuclear protein, identified by its position in a two-dimensional separation of cell proteins, is also transformation-sensitive and is preferentially synthesized in the S phase. We establish here that PCNA and cyclin are identical, and show that PCNA is an acidic nuclear protein of apparent molecular weight 35,000.     

Synaptic boutons in the hippocampus: Changes are produced by age and experience

Zusammenfassung Erstmaliger morphometrischer Nachweis bei 2 Gruppen reifer, altersunterschiedlicher Ratten, dass die Zahl der Synapsen im Hippocampus mit dem Alter zunimmt, wobei die effektive Steigerungsrate auch mit Umwelteinflüssen zusammenhängen könnte.

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This work was supported by grants from the U.S. National Institutes of Health to JJB (No. NS-06164) and to LEW,Jr., (No. NS-09358) and funds from the Center for Neurobiological Sciences of the University of Florida (No. NIH-MH-10320).     

Slavery in the subfamily dolichoderinae (F. Formicidae) and its ecological consequences

Summary Evidence of slave-making habits in 2 species of the subfamily Dolichoderinae has been found in arid habitats of western North America. The enslaved species are of the subfamilies Myrmicinae and Formicinae. In previously reported cases of slavery in ants, both the slave-making and enslaved species are of the subfamily Formicinae., In the 2 new cases of slavery reported here, presence of slaves of another species in a colony significantly increases the breadth of diet and/or the range of temperatures at which the colony forages.     

de Broglie Waves as the “Bridge of Becoming” Between Quantum Theory and Relativity

It is hypothesized that de Broglie’s ‘matter waves’ provide a dynamical basis for Minkowski spacetime in an antisubstantivalist or relational account. The relativity of simultaneity is seen as an effect of the de Broglie oscillation together with a basic relativity postulate, while the dispersion relation from finite rest mass gives rise to the differentiation of spatial and temporal axes. Thus spacetime is seen as not fundamental, but rather as emergent from the quantum level. A result by Solov’ev which demonstrates that time is not an applicable concept at the quantum level is adduced in support of this claim. Finally, it is noted that de Broglie waves can be seen as the “bridge of becoming” discussed by (2005).     

De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous.