Integrated proteomic and glycoproteomic characterization of human high-grade serous ovarian carcinoma

Many gene products exhibit great structural heterogeneity because of an array of modifications. These modifications are not directly encoded in the genomic template but often affect the functionality of proteins. Protein glycosylation plays a vital role in proper protein functions. However, the analysis of glycoproteins has been challenging compared with other protein modifications, such as phosphorylation. Here, we perform an integrated proteomic and glycoproteomic analysis of 83 prospectively collected high-grade serous ovarian carcinoma (HGSC) and 23 non-tumor tissues. Integration of the expression data from global proteomics and glycoproteomics reveals tumor-specific glycosylation, uncovers different glycosylation associated with three tumor clusters, and identifies glycosylation enzymes that were correlated with the altered glycosylation. In addition to providing a valuable resource, these results provide insights into the potential roles of glycosylation in the pathogenesis of HGSC, with the possibility of distinguishing pathological outcomes of ovarian tumors from non-tumors, as well as classifying tumor clusters

Floor area concession incentives as planning instruments to promote green building: A critical review of international practices

Gross Floor Area (GFA) concession scheme, as a planning incentive, is developed from the notion of “make developers pay” in UK in 1990. It rewards developers additional GFA in exchange for public amenities so that government could save that amount of money. This paper carries out a review of GFA concession scheme in Hong Kong and Singapore to synergize the key features and success factors of its implementation. Reasons for its effectiveness were discussed from the perspective of political, economical, and business issues. Based on case studies, the key features of “Floor Area Concession Schemes” are discussed, including 1) very effective in places with high land value; 2) influencing built environment positively and negatively; 3) ensuring the buildings get certified by green building (GB) rating system. This paper identifies key success factors, comprising 1) common goal but different interests shared by developers and governments; 2) a bonus cap; 3) regular review and revision of the scheme; 4) links between planning objectives and GB technology and design practice, which will be discussed. These help formulate a general approach or model of “Floor Area Concession Schemes” for promoting green building.OTBArchitecture and The Built Environmen

Modeling the green building (GB) investment decisions of developers and end-users with transaction costs (TCs) considerations

The paper, through a “regenerative” lens, has focused upon a new conceptual game system involving transaction costs (TCs) for creating a more accessible green buildings (GB) market. Individual stakeholders steadfastly guard their own interests in any investment decision, which seldom considers any positive gains to society. Green buildings, branded as partial public goods, involve rational and irrational factors, incurring extra transaction costs (TCs) and affecting the willingness of the stakeholders to take part. This paper examines how to reduce the TCs incurred during the game played in the decision-making process with the ultimate aim of promoting GB. In the game model, the developers and end-users negotiate and bargain over the TCs caused by GB in comparison with its conventional counterpart. The findings are that 1) TCs are the overriding barriers impeding the development of the GB market. Reducing TCs will facilitate supply and demand in the GB market; 2) the equilibrium payoffs for the developer and the end-user are proportional to their bargaining powers (the higher the bargaining power is, the more benefit it will gain from the GB transaction); 3) strengthening the bargaining power of the developer can increase the expected utility of developing GB; and 4) more fake GB products or less credible developers will result in higher TCs for the end-users and therefore lower payoffs will be expected. The findings stress that the choice between developers & end-users over investing in GB is a complex game problem, where TCs could be conceptualized and showed their important role. By minimizing the TCs incurred in the complex decision of GB, it will not only benefit themselves but also bring net regenerative outcomes to society.Housing Quality and Process InnovationOTB Research Institute for the Built Environmen

Knowledge and concerns of newly diagnosed NIDDM patients in Singapore

10.1016/0168-8227(91)90125-WDiabetes Research and Clinical Practice12111-18DRCP

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders