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.     

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface‐engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.     

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.     

Patterns of stability in adult attachment: An empirical test of two models of continuity and change.

One of the core assumptions of attachment theory is that attachment representations are stable over time. Unfortunately, the data on attachment stability have been ambiguous, and as a result, alternative theoretical perspectives have evolved to explain them. The objective of the present research was to evaluate alternative models of stability by studying adults in 2 intensive longitudinal investigations. Specifically, we assessed attachment representations in 1 sample (N = 203) daily over a 30-day period and in the other sample (N = 388) weekly over a year. Analyses show that the patterns of stability that exist in adult attachment are most consistent with a prototype model—a model assuming that there is a stable factor underlying temporary variations in attachment. Moreover, although the Big Five personality traits exhibited a pattern of stability that was similar to that of attachment, they did not account for the stability observed in attachment. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Impacts of stress on estimation performance in Hong Kong

Cost estimation not only requires precise technical and analytical input from estimators but also involves the use of subjective judgement. An investigation on the impact of stress on estimation performance was conducted involving 177 professional estimators in Hong Kong. Using correlation analysis, regression analysis and structural equation modelling, the relationships between stress and various aspects of estimation performance are examined and a causal structural model is developed. The results indicate that stress is a cause of negative estimation performance (resulting in weak interpersonal relationships, unfamiliarity with organization and ineffective process), while, simultaneously, it is beneficial to the professional estimation performance. Furthermore, there is an inverted U‐shaped relationship between stress and the organizational relationship.     

The Lysosomal Protein Saposin B Binds Chloroquine

Chloroquine (CQ) has been widely used in the treatment of malaria since the 1950s, though toxicity and resistance is increasingly limiting its use in the clinic. More recently, CQ is also becoming recognized as an important therapeutic compound for the treatment of autoimmune disorders and has shown activity as an anticancer agent. However, the full extent of CQ pharmacology in humans is still unclear. Herein, we demonstrate that the lysosomal protein saposin B (sapB), critical for select lipid degradation, binds CQ with implications for both CQ function and toxicity. Using isothermal titration calorimetry (ITC) and fluorescence quenching experiments, CQ was shown to bind to the dimeric form of sapB at both pH 5.5 and pH 7.4 with an average binding affinity of 2.3×10⁴ m ^?1. X‐ray crystallography confirmed this, and the first complete crystal structure of sapB with a bound small molecule (CQ) is reported. The results suggest that sapB might play a role in mitigating CQ‐based toxicity and that sapB might itself be overwhelmed by CQ causing impaired lipid degradation.