Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome

With an incidence of ~1 in 800 births, Down syndrome (DS) is the most com- mon chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA 21 that directly contribute to cognitive de fi cits remain incompletely understood. Here, we found that the HSA21- encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued de fi cits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes

Hybrid fiber reinforced self-compacting concrete: fiber synergy at low fber volume fraction

In most cases, fiber reinforced self-compacting concrete (FRSCC) contains only one type of fiber. The use of two or more types of fibers in a suitable combination may potentially not only improve the overal properties of self-compacting concrete, but may also result in performance synergie. The combining of fibers, often called hybridization, is investigated in this paper for a cimentetious matrix. Control, single, two fibers hybrid composites were cast using different fiber type steel and polypropylene with different sizes. Flexural toughness tests were performed and results were extensively analysed to identify synergy, if any, associated with various fiber combinations. Based on various analysis schemes, the paper identifies fiber combinations that demonstrate maximum synergy in terms of flexural toughness. Journal of Civil Engineering Research and Practice Vol. 3(1) 2006: 21-2