Does Bisphenol A Confer Risk of Neurodevelopmental Disorders? What We Have Learned from Developmental Neurotoxicity Studies in Animal Models

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, such as attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior-associated neurodevelopmental disorders. Consistent with neuronal phenotypes caused by BPA, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes the current literature on the developmental neurotoxicity of BPA in laboratory animals with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.     

Phage‐mediated transfer of virulence genes

Bacteriophages as accessory genetic elements play a crucial role in the dissemination of genes and the promotion of genetic diversity within bacterial populations. Such horizontal transfer of DNA is critical in the emergence of new pathogenic organisms, through the dissemination of genes encoding virulence factors such as toxins, adhesins and agressins. Phages can transfer genes that are not necessary for bacteriophage persistence and are generally recognised by their ability to convert their host bacteria to new phenotypes. This phenomenon is known as phage conversion. If such converting genes encode for virulence factors, the consequences of phage infection may include increased virulence of the host bacteria, and the conversion of a non‐pathogenic strain to a potentially dangerous pathogen. A number of virulence factors in bacteria causing diseases in plants, animals and humans are encoded by converting phages, the vast majority of which are temperate as opposed to lytic in nature. © 2001 Society of Chemical Industry     

Designing intersections—designing subjectivity: Feminist theory and praxis in a sex discrimination legislation system

This paper looks at the intersections between feminist epistemology, feminist jurisprudence and research on artificial intelligence and the law. It is suggested that feminist theory highlights the role of subjectivity which is ignored in the traditional epistemology of AI systems. This allows AI systems to appear to be “perspectiveless” when they may be tacitly used in a normative role which ignores alternative knowledges. The paper looks at the Cyc system as an example. In developing an expert system to advise on Sex Discrimination law a number of lessons are learned both from the Forms Helper system and more particularly from feminist jurisprudence and from the critique of AI from feminist epistemology.     

Dietary Influences on Bovine Milk cis-9,trans-11-Conjugated Linoleic Acid Content

The effects of grass dry matter (DM) allowance and dietary supplements of full fat rapeseeds on levels of cis-9,trans-11 octadecadienoic (CLA) acid in bovine milk were investigated. Grass allowance of 16 kg/(cow*day) resulted in reduced (p<0.05) milk fat CLA levels (3.91 mg CLA/g fat) compared to 20 kg/(cow*day) after 19 wk treatment. CLA levels increased in milk fat from cows on a high-rapeseed-supplemented diet (p<0.001) (1650 g/(cow*day) full fat rapeseed) compared to the control (pasture) and low rapeseed (p<0.01) (825 g/(cow*day) full fat rapeseed) supplemented diets. The variation in milk fat CLA levels among individual cows over both trials was 1.5–16 mg/g.     

Photoinducible Oncometabolite Detection

Dysregulated metabolism can fuel cancer by altering the production of bioenergetic building blocks and directly stimulating oncogenic gene-expression programs. However, relatively few optical methods for the direct study of metabolites in cells exist. To address this need and facilitate new approaches to cancer treatment and diagnosis, herein we report an optimized chemical approach to detect the oncometabolite fumarate. Our strategy employs diaryl tetrazoles as cell-permeable photoinducible precursors to nitrileimines. Uncaging these species in cells and cell extracts enables them to undergo 1,3-dipolar cycloadditions with endogenous dipolarophile metabolites such as fumarate to form pyrazoline cycloadducts that can be readily detected by their intrinsic fluorescence. The ability to photolytically uncage diaryl tetrazoles provides greatly improved sensitivity relative to previous methods, and enables the facile detection of dysregulated fumarate metabolism through biochemical activity assays, intracellular imaging, and flow cytometry. Our studies showcase an intersection of bioorthogonal chemistry and metabolite reactivity that can be applied for biological profiling, imaging, and diagnostics.