Assembly and structural analysis of a covalently closed nano-scale DNA cage

The inherent properties of DNA as a stable polymer with unique affinity for partner molecules determined by the specific Watson–Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited for decades in the design of a variety of artificial substrates for investigations of DNA-interacting enzymes. More recently, strategies for synthesis of more complex two-dimensional (2D) and 3D DNA structures have emerged. However, the building of such structures is still in progress and more experiences from different research groups and different fields of expertise are necessary before complex DNA structures can be routinely designed for the use in basal science and/or biotechnology. Here we present the design, construction and structural analysis of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron, as defined by the double-stranded DNA helices that assembles from eight oligonucleotides with a yield of ∼30%. As demonstrated by Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses the eight-stranded DNA structure has a central cavity larger than the apertures in the surrounding DNA lattice and can be described as a nano-scale DNA cage, Hence, in theory it could hold proteins or other bio-molecules to enable their investigation in certain harmful environments or even allow their organization into higher order structures

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition

A Hybrid Multiple Criteria Decision-Making Technique to Evaluate Regional Intellectual Capital: Evidence from China

With the dawn of economic globalization and the knowledge economy, intellectual capital has become the most important factor to determine economic growth. However, due to resource endowment, location conditions, policy differences, and other factors, provinces in China show sizeable differences in regional intellectual capital (RIC), which affects the coordinated development of the regional economy. Evaluating RIC is a typical multiple-criteria decision-making (MCDM) problem. Therefore, this study employs a set of MCDM techniques to solve this problem. First, the Delphi method is used to determine the formal decision structure based on a systematic literature review. A novel hybrid method, namely, the Grey-based Decision-Making Trial and Evaluation Laboratory (DEMATEL) and Analytic Network Process (ANP), i.e., GDANP, is employed to obtain the relative weight of each criterion. Finally, based on the data of 31 provinces in China, the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) is used to evaluate the RIC. According to the questionnaires filled out by an expert panel, we establish an evaluation index of RIC with 21 criteria. Based on the results of empirical study, the level of RIC in different regions in China is quite different. Furthermore, the RIC ranking is largely consistent with the provincial gross domestic product (GDP) ranking, in line with the current status of development in the regions. Indeed, this paper shows that the proposed hybrid method can effectively measure the level of RIC

Downregulation of FAK-Related Non-Kinase Mediates the Migratory Phenotype of Human Fibrotic Lung Fibroblasts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89993/1/white-downregulation_fak-related_non-kinase.pd

FAK-Related Nonkinase Is a Multifunctional Negative Regulator of Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease whose underlying molecular mechanisms are largely unknown. Herein, we show that focal adhesion kinase–related nonkinase (FRNK) plays a key role in limiting the development of lung fibrosis. Loss of FRNK function in vivo leads to increased lung fibrosis in an experimental mouse model. The increase in lung fibrosis is confirmed at the histological, biochemical, and physiological levels. Concordantly, loss of FRNK function results in increased fibroblast migration and myofibroblast differentiation and activation of signaling proteins that drive these phenotypes. FRNK-deficient murine lung fibroblasts also have an increased capacity to produce and contract matrix proteins. Restoration of FRNK expression in vivo and in vitro reverses these profibrotic phenotypes. These data demonstrate the multiple antifibrotic actions of FRNK. More important, FRNK expression is down-regulated in human IPF, and down-regulation of FRNK in normal human lung fibroblasts recapitulates the profibrotic phenotype seen in FRNK-deficient cells. The effect of loss and gain of FRNK in the experimental model, when taken together with its down-regulation in human IPF, suggests that FRNK acts as an endogenous negative regulator of lung fibrosis by repressing multiple profibrotic responses