Global Expansion of National Securities Laws: Extraterritoriality and Jurisdictional Conflicts

[Excerpt] “As securities fraud has grown increasingly transnational, it has become necessary to expand the reach of anti-fraud provisions to persons and entities participating in global securities markets. So far, however, no single antifraud provision exists to govern the entire global marketplace. Although each country strives to combat international securities fraud by using its own regulatory regime, problems can develop when extraterritorial application of national securities laws leads to regulatory overlapping or conflicts. In light of these problems, it is necessary to set forth clear guidelines for determining whether national securities laws can apply extraterritorially and, if so, how far they can extend. The U.S., in particular, has longstanding and extensive experience in seeking extraterritorial application of national securities laws. In doing so, the U.S. has developed several tests to justify extraterritoriality, and has bolstered a statutory basis for extraterritorial application of anti-fraud prohibitions in actions brought by the U.S. Securities and Exchange Commission (SEC) or the U.S. Department of Justice (DOJ).

Exclusive Endoscopic Resection of Nasopharyngeal Papillary Adenocarcinoma via Combined Transnasal and Transoral Approach

Low grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is an extremely rare variant of nasopharyngeal cancer, which exhibits distinct clinicopathological characteristics. Surgical resection has been regarded as the principal treatment. For this, transpalatal or transfacial approach has been classically used for exposure of the field. Up for now, there has been no report on applying endoscopic approach for this disease, which could be an effective alternative to minimize possible morbidities of palatotomy or maxillotomy. Endoscopic approach can be justified considering narrow extent and indolent behavior of LGNPPA. We report a patient with LGNPPA, which was successfully resected exclusively by endoscopic visualization. Our case exhibited narrow-based exophytic features with compatible immunopathologic profiles of LGNPPA. Exclusive endoscopic resection can be effective and less-morbid modality for this rare disease as in this case

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

Background A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Methods Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Results Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. Conclusion In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.This work was supported by the Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2018R1A2B2002923) to S.J.B. This work was also partially supported by a clinical research grant (NCC1810150) provided by the National Cancer Center to J.R. and S.J.B. The Fig. 7 Nootkatone controls the NAG-1 expression at the transcriptional level. a Nootkatone increases NAG-1 promoter activity. HCT-116 cells were transfected with pNAG-1 − 1086/+ 41 luciferase and pRL-null plasmid. The cells were treated with EtOH or various concentrations of nootkatone for 24 h, and luciferase activity was measured. The y-axis refers to the ratio of firefly luciferase over renillar luciferase activity. The EtOH-treated cells were set as 1.0. Statistical significance was displayed as *p < 0.05, ***p < 0.001 versus EtOH-treated cells. The data represent mean ± SD from three independent experiments. b Three deletion NAG-1 promoter constructs were co-transfected with pRL-null vector into HCT-116 cells. The cells were treated with EtOH or 100 μM of nootkatone for 24 h, and luciferase activity was measured. Fold induction refers to the ratio of luciferase activity in nootkatone-treated cells versus EtOH-treated cells. Statistical significance was displayed as **p < 0.01 and ***p < 0.001 versus EtOH-treated cells. The data represent mean ± SD from three independent experiments. c HCT-116 cells were co-transfected with wild type pNAG-1 − 133/+ 41 in the presence of empty or EGR-1 expression vector. Cells were subsequently treated with 100 μM nootkatone for 24 h. The results are presented as means ± S.D. of three independent transfections. d Western blot of EGR-1 protein in the presence of nootkatone. β-actin was used as loading control. e Luciferase activity of EGR-1 promoter-luciferase construct (pEGR-1260-LUC). The cells were treated with EtOH or nootkatone for 24 h prior to measurement of luciferase activity. Fold induction refers to the ratio of luciferase activity in nootkatone-treated cells compared to EtOH-treated cells. Statistical significance represented as *p < 0.05, ***p < 0.001 versus EtOH-treated cells. n.s. represents not significant. The data represent mean ± SD from four independent experiments Yoo et al. BMC Cancer (2020) 20:881 Page 10 of 12 funding agency did not have any influence in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Grid selection strategy for high-resolution cryo-EM

Cryo-electron microscopy (cryo-EM) is a revolutionary technique to study the three-dimensional structure of macromolecules and theirs complexes at molecular resolution. The first step in preparing samples for cryo-EM is to select and optimize the right grid for the specimen. This screening process needs consideration in many aspects including concentration and stability of the specimen, compatibility with grid material and optimum ice thickness across the grid. Importantly, the best signal-to-noise ratio (SNR) for a micrograph is closely related to vitrifying the grid sample with the optimum imaging condition. Here we describe overall strategies for grid selection and optimization by understanding the properties of grids and a variety of techniques for grid treatment for high-resolution electron micrographs. This review also describes the utilization of various specimen supports including amorphous carbon, graphene and functionalized support films.N

Color 2018

Cover for Color 2018, from the RISD Library Zine Collection.https://digitalcommons.risd.edu/specialcollections_zinecollection/1719/thumbnail.jp

Cryo-EM structures of GroEL:ES2 with RuBisCO visualize molecular contacts of encapsulated substrates in a double-cage chaperonin

The GroEL/GroES chaperonin system assists the folding of many proteins, through conformational transitions driven by ATP hydrolysis. Although structural information about bullet-shaped GroEL:ES1 complexes has been extensively reported, the substrate interactions of another functional complex, the foot-ball-shaped GroEL:ES2, remain elusive. Here, we report single-particle cryo-EM structures of reconstituted wild-type GroEL:ES2 complexes with a chemically denatured substrate, ribulose-1,5-bisphosphate carboxylase oxygenase (RuBisCO). Our structures demonstrate that native-like folded RuBisCO density is captured at the lower part of the GroEL chamber and that GroEL&apos;s bulky hydrophobic residues Phe281, Tyr360, and Phe44 contribute to direct contact with RuBisCO density. In addition, our analysis found that GroEL:ES2 can be occupied by two substrates simultaneously, one in each chamber. Together, these observations provide insights to the football-shaped GroEL:ES2 complex as a functional state to assist the substrate folding with visualization.Y