NQO2 is a reactive oxygen species generating off-target for acetaminophen

[Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity

View-based modelling of human visual navigation errors

View-based and Cartesian representations provide rival accounts of visual navigation in humans, and here we explore possible models for the view-based case. A visual “homing” experiment was undertaken by human participants in immersive virtual reality. The distributions of end-point errors on the ground plane differed significantly in shape and extent depending on visual landmark configuration and relative goal location. A model based on simple visual cues captures important characteristics of these distributions. Augmenting visual features to include 3D elements such as stereo and motion parallax result in a set of models that describe the data accurately, demonstrating the effectiveness of a view-based approach

Enhancement of psychosocial treatment with D-cycloserine: models, moderators, and future directions

Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).F31 MH103969 - NIMH NIH HHS; K24 DA030443 - NIDA NIH HHS; R34 MH099309 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; R34 MH099318 - NIMH NIH HH

DNA and pacific commensal models : applications, construction, limitations, and future prospects

Components of the Pacific transported landscape have been used as proxies to trace the prehistoric movement of humans across the Pacific for almost two decades. Analyses of archaeological remains and DNA sequences of plants, animals, and microorganisms moved by or with humans have contributed to understanding prehistoric migration, trade, exchange, and sometimes revealed the geographic origins of particular plants and animals. This paper presents the basic elements of a DNA-based commensal model and discusses the phylogenetic and population genetic approaches these models employ. A clear delineation of the underlying assumptions of these models and the background information required to construct them have yet to appear in the literature. This not only provides a framework with which to construct a commensal model but also highlights gaps in current knowledge. The ways in which commensal models have enriched archaeological reconstructions will be highlighted, as will their current limitations. With these limitations in mind, options will be outlined for augmenting commensal models through the application of established techniques and new technologies in order to provide the best tools for reconstructing ancient human mobility and behavior in the Pacific and beyond

Augmenting human memory using personal lifelogs

Memory is a key human facility to support life activities, including social interactions, life management and problem solving. Unfortunately, our memory is not perfect. Normal individuals will have occasional memory problems which can be frustrating, while those with memory impairments can often experience a greatly reduced quality of life. Augmenting memory has the potential to make normal individuals more effective, and those with significant memory problems to have a higher general quality of life. Current technologies are now making it possible to automatically capture and store daily life experiences over an extended period, potentially even over a lifetime. This type of data collection, often referred to as a personal life log (PLL), can include data such as continuously captured pictures or videos from a first person perspective, scanned copies of archival material such as books, electronic documents read or created, and emails and SMS messages sent and received, along with context data of time of capture and access and location via GPS sensors. PLLs offer the potential for memory augmentation. Existing work on PLLs has focused on the technologies of data capture and retrieval, but little work has been done to explore how these captured data and retrieval techniques can be applied to actual use by normal people in supporting their memory. In this paper, we explore the needs for augmenting human memory from normal people based on the psychology literature on mechanisms about memory problems, and discuss the possible functions that PLLs can provide to support these memory augmentation needs. Based on this, we also suggest guidelines for data for capture, retrieval needs and computer-based interface design. Finally we introduce our work-in-process prototype PLL search system in the iCLIPS project to give an example of augmenting human memory with PLLs and computer based interfaces

The dimensions of personality in humans and other animals: A comparative and evolutionary perspective

This paper considers the structure and proximate mechanisms of personality in humans and other animals. Significant similarities were found between personality structures and mechanisms across species in at least two broad traits: Extraversion and Neuroticism. The factor space tapped by these personality dimensions is viewed as a general integrative framework for comparative and evolutionary studies of personality in humans and other animals. Most probably, the cross-species similarities between the most broad personality dimensions like Extraversion and Neuroticism as well as other Big Five factors reflect conservative evolution: constrains on evolution imposed by physiological, genetic and cognitive mechanisms. Lower-order factors, which are more species- and situation-specific, would be adaptive, reflecting correlated selection on and trade-offs between many traits