PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems.

Interfacing gene delivery vehicles with biomaterials has the potential to play a key role in diversifying gene transfer capabilities, including localized, patterned, and controlled delivery. However, strategies for modifying biomaterials to interact with delivery vectors must be redesigned whenever new delivery vehicles and applications are explored. We have developed a vector-independent biomaterial platform capable of interacting with various adeno-associated viral (AAV) serotypes. A water-soluble, cysteine-tagged, recombinant protein version of the recently discovered multi-AAV serotype receptor (AAVR), referred to as cys-AAVR, was conjugated to maleimide-displaying polycaprolactone (PCL) materials using click chemistry. The resulting cys-AAVR-PCL system bound to a broad range of therapeutically relevant AAV serotypes, thereby providing a platform capable of modulating the delivery of all AAV serotypes. Intramuscular injection of cys-AAVR-PCL microspheres with bound AAV vectors resulted in localized and sustained gene delivery as well as reduced spread to off-target organs compared to a vector solution. This cys-AAVR-PCL system is thus an effective approach for biomaterial-based AAV gene delivery for a broad range of therapeutic applications

Sustainable Conservation of a Difficult Heritage in South Korea: Mapping the Conservation Resources of Sorok-do Island, Hansen’s Disease Site

South Korea’s Sorok-do island bears witness to the 100-year history of the Sorok-do hospital and the village for Hansen’s disease (leprosy) patients. All the facilities of Sorok-do were established by the Japanese imperial authorities, and the collective memories of social isolation and discrimination against Hansen’s disease patients were deeply embedded in this island during the colonial and post-colonial periods. Despite changing perceptions toward the conservation of the island’s history since the 1990s, the island’s deep collective memory remains at risk due to the increasing number of incoming settlers and the shrinking number of Hansen’s disease patients since the opening of the Sorok Bridge in 2009. Taking into consideration the historical lack of critical engagement with difficult heritage conservation in South Korea, this paper introduces a novel approach to sustainable conservation, using as a case study the Sorok-do island. We collected data using archival research, participant observation and semi-structured in-depth interviews, and analyzed them by using a position-mapping method. This paper examines the island’s multifaceted, shifting processes within its history, urban structure, and changing social meanings, and offers a new set of criteria for long-term strategies that will ensure both tangible and intangible types of conservation resources.</jats:p

A Comparative Analysis of Three Major Transfer Airports in Northeast Asia Focusing on Incheon International Airport Using a Conjoint Analysis

Due mainly to the privatization and commercialization of airline companies and deregulation of the aviation rules, the demand for air transport has continuously been increasing. Airport authorities state that transfer passengers, who contribute to the large portion of the airports’ profits, are gaining much more importance, particularly in the Northeast Asia region where the air transport industry is very vital. Therefore, this study aims to investigate the competitiveness of IIA (Incheon International Airport) with other major airports located in Northeast Asia in passenger transfers made between Southeast Asia and China to North America using Conjoint Analysis. Results have indicated that airport brand is the most important attribute for the competitiveness of airport, followed by cost, connectivity and duty free shops. In further analysis focusing on brand value of the three airports measured by the use of transfer passengers, it was revealed that IIA needs more effort in developing their brand identity to become the leading transfer hub airport. Based on the results, recommendations for increasing the brand value have also been suggested