tracks

tracks January 12-February 8, 1999 Jaffe-Friede & Strauss Galleries, Hopkins Center, Dartmouth College jin soo kim artist-in-residencehttps://via.library.depaul.edu/oral_his_gallery/1086/thumbnail.jp

DIG-seq: a genome-wide CRISPR off-target profiling method using chromatin DNA

To investigate whether and how CRISPR-Cas9 on-target and off-target activities are affected by chromatin in eukaryotic cells, we first identified a series of identical endogenous DNA sequences present in both open and closed chromatin regions and then measured mutation frequencies at these sites in human cells using Cas9 complexed with matched or mismatched sgRNAs. Unlike matched sgRNAs, mismatched sgRNAs were highly sensitive to chromatin states, suggesting that off-target but not on-target DNA cleavage is hindered by chromatin. We next performed Digenome-seq using cell-free chromatin DNA (now termed DIG-seq) and histone-free genomic DNA in parallel and found that only a subset of sites, cleaved in histone-free DNA, were cut in chromatin DNA, suggesting that chromatin can inhibit Cas9 off-target effects in favor of its genome-wide specificity in cells.

Alcoholism and Diabetes Mellitus

Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism

Flow Characteristics Around Step-Up Street Canyons with Various Building Aspect Ratios

We investigate the flow characteristics around step-up street canyons with various building aspect ratios (ratio of along-canyon building length to street-canyon width, and upwind building height to downwind building height) using a computational fluid dynamics (CFD) model. Simulated results are validated against experimental wind-tunnel results, with the CFD simulations conducted under the same building configurations as those in the wind-tunnel experiments. The CFD model reproduces the measured in-canyon vortex, rooftop recirculation zone above the downwind building, and stagnation point position reasonably well. We analyze the flow characteristics, focusing on the structural change of the in-canyon flows and the interaction between the in- and around-canyon flows with the increase of building-length ratio. The in-canyon flows undergo development and mature stages as the building-length ratio increases. In the development stage (i.e., small building-length ratios), the position of the primary vortex wanders, and the incoming flow closely follows both the upstream and downstream building sidewalls. As a result, increasing momentum transfer from the upper layer contributes to a momentum increase in the in-canyon region, and the vorticity in the in-canyon region also increases. In the mature stage (i.e., large building-length ratios), the primary vortex stabilizes in position, and the incoming flow no longer follows the building sidewalls. This causes momentum loss through the street-canyon lateral boundaries. As the building-length ratio increases, momentum transfer from the upper layer slightly decreases, and the reverse flow, updraft, and streamwise flow in the in-canyon region also slightly decrease, resulting in vorticity reduction