"Weight of evidence" (WOE) is a common term in the published scientific and policy-making literature, most often seen in the context of risk assessment (RA). Its definition, however, is unclear. A systematic review of the scientific literature was undertaken to characterize the concept. For the years 1994 through 2004, PubMed was searched for publications in which "weight of evidence" appeared in the abstract and/or title. Of the 276 papers that met these criteria, 92 were selected for review: 71 papers published in 2003 and 2004 (WOE appeared in abstract/title) and 21 from 1994 through 2002 (WOE appeared in title). WOE has three characteristic uses in this literature: (1) metaphorical, where WOE refers to a collection of studies or to an unspecified methodological approach; (2) methodological, where WOE points to established interpretative methodologies (e.g., systematic narrative review, meta-analysis, causal criteria, and/or quality criteria for toxicological studies) or where WOE means that "all" rather than some subset of the evidence is examined, or rarely, where WOE points to methods using quantitative weights for evidence; and (3) theoretical, where WOE serves as a label for a conceptual framework. Several problems are identified: the frequent lack of definition of the term "weight of evidence," multiple uses of the term and a lack of consensus about its meaning, and the many different kinds of weights, both qualitative and quantitative, which can be used in RA. A practical recommendation emerges: the WOE concept and its associated methods should be fully described when used. A research agenda should examine the advantages of quantitative versus qualitative weighting schemes, how best to improve existing methods, and how best to combine those methods (e.g., epidemiology's causal criteria with toxicology's quality criteria).

Weight of evidence: a review of concept and methods.

Environmental aromatic acids are transformed to chemical energy in bacteria that possess the requisite secondary pathways. Some of these pathways rely on the activation of the aromatic acid by coenzyme A (CoA) thioesterification catalyzed by an aromatic acid: CoA ligase. Adaptation of such pathways to the bioremediation of man-made pollutants such as polychlorinated biphenyl (PCB) and dichlorodiphenyltrichloroethane (DDT) requires that the chlorinated benzoic acid byproduct that is formed be able to be eliminated by further degradation. To take advantage of natural benzoic acid degrading pathways requiring initial ring activation by thioesterification, the pathway aromatic acid:CoA ligase must be an effective catalyst with the chlorinated benzoic acid. This study, which focuses on the 4-chlorobenzoate:CoA ligase (CBL) of the 4-monochlorobiphenyl degrading bacterium Alcaligenes sp. strain ALP83, was carried out to determine if the 4-chlorobenzoate binding site of this enzyme can be transformed by rational design to recognize the chlorobenzoic acids formed in the course of breakdown of other environmental PCB congeners. The fundamental question addressed in this study is whether it is possible to add or subtract space from the substrate-binding pocket of this ligase (to complement the topology of the unnatural aromatic substrate) without causing disruption of the ligase catalytic machinery. Herein, we report the results of a substrate specificity analysis that, when interpreted within the context of the X-ray crystal structures, set the stage for the rational design of the ligase for thioesterification of two PCB-derived chlorobenzoic acids. The ligase was first optimized to catalyze CoA thioesterification of 3,4-dichlorobenzoic acid, a poor substrate, by truncating Ile303, a large hydrophobic residue that packs against the ring meta-C(H) group. The structural basis for the approximately 100-fold enhancement in the rate of 3,4-dichlorobenzoate thioesterification catalyzed by the I303A and I303G CBL mutants was validated by determination of the crystal structure of the 3,4-dichlorobenzoate-bound enzymes. Determinations of the structures of I303 mutant complexes of 3-chlorobenzoate, a very poor substrate, revealed nonproductive binding as a result of the inability of the substrate ring C(4)H group to fill the pocket that binds the C(4)Cl group of the native substrate. The C(4)Cl pocket of the CBL I303A mutant was then reduced in size by strategic amino acid replacement. A 54-fold improvement in catalytic efficiency was observed for the CBL F184W/I303A/V209T triple mutant. The results of this investigation are interpreted as evidence that the plasticity of the ligase catalytic scaffold is sufficient to allow expansion of substrate range by rational design. The combination of structural and kinetic analyses of the constructed mutants proved to be an effective approach to engineering the ligase for novel substrates.

/pdf/rational-redesign-of-the-4-chlorobenzoate-binding-site-of-4-456a6gso8c.pdf

Rational redesign of the 4-chlorobenzoate binding site of 4-chlorobenzoate: coenzyme a ligase for expanded substrate range.

In “Potential Human Cancer Risks From Exposure to PCBs: A Tale of Two Evaluations,”1 R. Golden, J. Doull, W. Waddell, and J. Mandell addressed three primary concerns with the Toxicological Profile ...

Comments on "Potential human cancer risks from exposure to PCBs: a tale of two evaluations".

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

M. Williams

Author Tools

Chat about Author

Papers

Comments on "Potential human cancer risks from exposure to PCBs: a tale of two evaluations".