Mouse hepatocyte overexpression of NF‐κB‐inducing kinase (NIK) triggers fatal macrophage‐dependent liver injury and fibrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109646/1/hep27348-sup-0001-suppinfo01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109646/2/hep27348.pd

The estimated glomerular filtration rate was U-shaped associated with abdominal aortic calcification in US adults: findings from NHANES 2013–2014

ObjectivesThe high incidence of abdominal aortic calcification (AAC) is well-documented in individuals with severe renal function decline. However, there is limited research on the historical relationship between estimated glomerular filtration rate (eGFR) and the risk of AAC occurrence in the general population undergoing routine medical examinations. The main objective of this study was to investigate the historical relationship between eGFR and AAC in the general population of the United States.MethodsWe performed a cross-sectional study using the National Health and Nutrition Examination Survey 2013–2014 database. Weighted multivariate linear regression models were used to estimate the associations of eGFR with AAC score. Smooth curve fitting and two-piecewise linear regression were employed to explore the potential non-linear relationship.ResultsA total of 2,978 participant (48.22% were male) aged 40–80 years were included in this study. The fully-adjusted model demonstrated a negative correlation between eGFR and AAC score (β = −0.015, 95% CI: −0.023 to −0.006). However, when applying the smooth curve fitting method, a U-shaped relationship was identified, and the inflection point was calculated at 76.43 ml/min/1.73 m2 using the two-piecewise linear regression model.ConclusionsThere was a U-shaped association between eGFR and AAC score in general US adults, with an inflection point at about 76.43 ml/min/1.73 m2

Ad Hoc Integration and Querying of Heterogeneous Online Distributed Databases

This dissertation provides an ad hoc integration methodology to manage and integrate heterogeneous online distributed databases on demand. The problem arises from an impending demand from scientific users to conveniently manage existing Web data along with the complexity involved in the construction of a functional data federation system using existing data integration technologies. We close this gap with a databases management framework accompanying novel Web data specification languages, wrapper generation technologies, and distributed query processing techniques. A major achievement of this dissertation is the establishment of a sound relational data model for Web data. Under this model, the Web becomes a synthetic extension of the traditional database systems. Consequently, a novice user of our system can cheaply integrate a large number of distributed Web sources with in-house databases for daily scientific data analysis purpose. The relational Web modeling leads to a practical ad hoc integration system - the Meteoroid system (a MEthodology for ad hoc inTEgration of Online distributed heteROgeneous Internet Data) - in the context of biological data interoperability. We identify that a main difficulty for ad hoc integration lies in the lack of a fully automated wrapper generation and maintenance technique for general semi-structured data such as HTML, XML and plain text documents. We address this issue through a thorough study of characteristics of online Web data and devise various automated wrapper techniques to facilitate robust data wrapping tasks. With this technique, form-based Web data and table-based Web data can be treated like traditional relational databases. A seamless interoperation environment for Web data and in-house databases is possible. Another difficulty impeding ad hoc integration is in the query processing for heterogeneous distributed sources, where conflict of data is common and on demand mediation of distributed sources is desirable. The dynamicity and unpredictability of Web data further complicate the query processing task. We studied limitations posed by the Web environment for integration query processing and developed innovative techniques to expedite the early appearance of available results. Finally we demonstrate a prototype system for ad hoc integration of heterogeneous biological data. In the system, visual Web-based interfaces guide the integration of heterogeneous data for novice users. A declarative environment is supported for ad hoc querying and management of distributed data sources

Supporting Remote User Defined Functions in Heterogeneous Biological Databases

Similar to most scientic studies, biological analyses demand a great deal of computations and simulations involving sophisticated tools that are often found geographically distributed over the Internet. A worldwide eort in genomics research has resulted in a powerful collection of publicly available sequence analysis tools. These tools often require specialized local services and domain knowledge to function correctly, rendering them unlikely candidates for integration into remote database applications. Thus, integration of heterogeneous \functions" still remains an open problem. Providing a reasonable framework for seamless integration of these tools with database query engines will enable application developers to exploit and harness the power of these eective analysis tools. In this paper, we present an integration framework for such tools by enabling access to them in a user transparent way as part of database queries. In our system, such online tools are abstracted as remote user dened functions (RUDF). An extended SQL DDL language, called the Internet Function Denition Language (IFDL), is presented for the specication and denition of RUDFs. The interface between database system and the Internet is implemented using a layer based on a language called the Hyper Text Query Language (HTQL). The separation of IFDL, DDL, HTQL and SQL DML oers several optimization opportunities and makes it possible to develop an architecture for interoperability of heterogeneous databases with RUDFs in more simple and ecient ways.

A small‐molecule inhibitor of NF‐κB‐inducing kinase (NIK) protects liver from toxin‐induced inflammation, oxidative stress, and injury

Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF‐κβ‐inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small‐molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK‐induced p100‐to‐p52 processing and inflammatory gene expression, both in vitro and in vivo. Furthermore, in vivo administration of B022 protected against not only NIK but also CCl4‐induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.—Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small‐molecule inhibitor of NF‐κβ‐inducing kinase (NIK) protects liver from toxin‐induced inflammation, oxidative stress, and injury. FASEB J. 31, 711–718 (2017). http://www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154426/1/fsb2fasebj3120840r.pd