The Role of NADPH oxidase 2 (NOX2) in High-Fat Diet-Induced Adiposopathy and Brain Dysfunction in a Mouse Model

Obesity can have numerous detrimental consequences, namely metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer, and Alzheimer’s disease. The pathogenesis and physiologic consequences of obesity are unknown, but they are often associated with increased inflammation and oxidative stress in both the body and in the brain. One factor that has been implicated in causing inflammation associated with a high fat diet is the enzyme NADPH oxidase, or NOX, specifically the subunit NOX2. Two studies were performed in order to assess the effects of a high fat diet in combination with a universal NOX2 deficiency and a NOX2 deficiency targeted to macrophages. The results of the first study indicate that the NOX2 knockout (NOX2KO) mice on a high fat diet do not experience all the deleterious metabolic and inflammatory effects in the body and brain to the same degree as wild-type mice. This suggests that a deficiency in NOX2 does offer protection from some of the deleterious effects of a high fat diet. It was also determined from the first study that NOX2 expression is localized to macrophages in the visceral adipose tissue. In order to target these macrophages, a second study was conducted. For this second study, a mouse model was genetically engineered with the intent of inhibiting NOX2 solely within macrophages. Similar to the first study, these macrophage-deficient NOX2 knockout (macNOX2KO) mice were placed on a high fat along with the NOX2-flox wild-type (WT-FL) mice. The results suggest that the macrophage-deficient NOX2 knockout mice were protected from the deleterious effects of a high fat diet. In summary, the deletion of NOX2 appears to offer a protective benefit against the deleterious effects of obesity in the context of a high fat diet. Specifically, the deletion of NOX2 in macrophages also offers this protection with the added benefit of targeting the deletion so as to not affect NOX2 functioning in other cells in the body

Is my Aha! bigger than yours? Investigating individual differences in the experience of insight

A Neural Network Theory (NNT) account of insight processes and individual differences in cognitive ability predicts that, compared to routine problem solving, insight experiences will be associated with less involvement of control functions and will occur less frequently among people with greater fluid ability. The present study investigated the role of fluid intelligence and metacognitive control in the elicitation of Aha experiences. Seventy-six participants, predominantly university students (84% female), attempted a set of problems, including classic insight, non-insight and riddles. Subjective experiences of insight, certainty and suddenness of the solution process were measured, using a purpose-built concurrent rating apparatus and retrospective report. Participants completed Raven’s Advanced Progressive Matrices (fluid intelligence) and an attention-switching task (metacognitive control). Hierarchical Generalised Linear Modelling was used to model Aha experiences as a function of item-level predictors (Level 1) and person-characteristics (Level 2). The overall odds of reporting an Aha experience were 0.42. Higher fluid intelligence, but not metacognitive control, was associated with reduced odds of reporting Aha on a problem (OR=0.88, 95% CI: 0.82,0.95), controlling for accuracy, solution suddenness, and verbal skills. Aha experiences were significantly associated with multiple theoretically meaningful retrospective and concurrent problem-solving experience ratings, with fluid intelligence moderating some associations. These findings support the NNT account of insight as a special process and fluid intelligence as a factor limiting the complexity, and accessible solution states from the initial problem representation, leading to the requirement for an alternative representation. The study demonstrates some methodological solutions to difficulties inherent in measuring insight. A chimpanzee named Sultan, two sticks, and a hard-to-reach banana; this is the scenario from which almost a century of research investigating “Aha!” experiences emerged (Ohlsson, 1992). Early Gestalt psychologist Wolfgang Kohler observed that after repeated attempts to reach the banana, Sultan entered a failure-induced sulk. However, he became suddenly re-energised, and purposefully joined two sticks together to retrieve the banana (Kohler, 1921 cited in Ohlsson 1992). How, after numerous attempts and apparent acceptance of failure, did the solution to this intractable problem suddenly appear in Sultan's consciousness? What processes simmering beyond conscious awareness conjured a fully formed solution and planted it so abruptly into Sultan's dormant and tortured mind? "Aha!" Aha experiences are thought to be indicative of a moment of insight and have historically been associated with exceptional creativity, scientific discovery and genius (Hill & Kemp, 2018; Metcalfe & Wiebe, 1987; Shen et al., 2016; Sternberg & Davidson, 1995). These experiences have been shown to be distinct neurophysiological phenomena (Bowden & Jung-Beeman, 2003; Kounios et al., 2006; Sandkühler & Bhattacharya, 2008; Tik et al., 2018) that facilitate memory (Danek et al., 2013), improve learning (Dominowski & Buyer, 2000), and provide motivation during difficult learning (Liljedahl, 2005). Current definitions of insight moments describe them as the occurrence of a solution or path to a solution suddenly and unexpectedly coming to mind following a pause in active thinking when a problem-solver feels unable to make further progress (Bowden et al., 2005; Sternberg & Davidson, 1995). Insight is asserted to be a special process that is distinct from analytical problem-solving (Knoblich et al., 1999; Ohlsson, 1992; Sternberg & Davidson, 1995). Analytical problem-solving is continuous and incremental and does not engender a salient Aha experience (Schooler et al., 1993). Despite a substantial body of research seeking to demystify these processes, the specialness of insight is still the subject of much debate. Recent research suggests that the lack of clarity is a result of the way insight is operationalised in many studies as “solving an insight problem” (Danek et al., 2016; Webb et al., 2016) without verifying that the problem-solver has experienced an Aha moment. These studies indicate that insight is not reliably evoked by these problems, suggesting the processes engaged in solving insight problems may be idiosyncratic (Danek et al., 2016; Webb et al., 2016). That is, it is possible that rather than task requirements, individual differences of the problem-solver influence whether or not insight processes are used to solve a problem and the subsequent occurence of an Aha experience. Two individual characteristics that may be relevant to the Aha experience are fluid intelligence and metacognitive control. Fluid intelligence is defined as the ability to use controlled and deliberate mental operations to solve problems, deduce patterns, identify relations and draw inferences (McGrew, 2009). Metacognitive control is a facet of metacognition that refers explicitly to the control processes involved in regulating and directing information processing resources (Nelson & Narens, 1990). Differing levels of these abilities may influence the cognitive processes engaged during problem-solving (Dix et al., 2016). Thus, the central aim of this study is to investigate whether individual differences in fluid intelligence or metacognitive control influence whether an Aha experience occurs upon problem-solving. The present study agrees with several others that an Aha reported by the problem-solver is verification that insight has occurred (Bowden et al., 2005; Danek et al., 2016; Webb et al., 2016). However, some researchers argue that Aha experiences occur randomly (Chuderski, 2014) or are related to post-solution affect of evaluations of the solution (Topolinski & Reber, 2010). The second aim of the present study is to determine if Aha moments are associated with problem-solving experiences that are indicative of a special process. Due to current limitations in methodology, a new device was developed to accomplish this aim. This is described in section 2.5

Transport behaviour and diffusion of telematics: a conceptual framework and empirical application

The potential impacts that may be expected from new information and telecommunicationsystems applied to transport are considerable. However, as is the case with anynew technological innovation, at the basis of success of transport telematics lies theacceptance by potential users, which suggests that there is a clear need to investigatethe user side of these technologies. Given this need to explore the interactionbetween human behaviour and transport telematics, the aim of this paper is toinvestigate behavioral factors and their interrelationships in the use and diffusion ofnew telematics technologies. We will focus our attention on those systems whichprovide information to various categories of users, viz. public transport users andprivate car users.A conceptual framework is presented that covers all variables of interest for theinvestigation of user responses to these technologies. An important explanatoryvariable for acceptance of new telematics technologies is user segmentation; it has tobe recognized that the effects of respective technological innovations will varybetween various groups of transport users. In analyzing in more detail the dynamics o

The relevance and use of information and telecommunication networks as strategic tools in the transport sector: a Dutch case study

New information and telecommunication technologies in the transport sector, often named `Advanced Transport Telematics' (ATT), play a key role in thenew European network economy, as they have the potential to offer new solutions to the emerging transport problems in Europe. However, the successfulexploitation of ATT in European transport markets depends on the technology being implemented in a way which meets the distinct needs of the differentroad user groups in order to achieve social acceptance and thereby political approval.It is therefore vitally important that decision makers (i.e. those influencing theadoption of ATT) have sufficient information on the needs of (commercial) road users and on the way they perceive ATT options in addressing those needs. The ATT market comprises a large number of actors from both the public and the private sector. At the demand side, some major potential market sectorscan be identified. In addition to private users, there are intermediate or collective users (e.g., road authorities) and commercial users (e.g., thefreight sector). In the latter case ATT may play a strategic role by facing the need of the freight sector to orient itself towards the opportunitiesoffered by theEuropean internal market, which has far-reaching impacts not only on organisations operating in intemational networks, but also on those operatingnationally.The aim of the underlying study is to investigate the potential ATT market among these main user and interest groups, where the range of telematicsapplications will be restricted to those applied to inter-urban road transport. The focus will be on collective users (road managers) and commercialusers (road freight operators). Surveys and in-depth interviews have been used to gather relevant information on the views, attitudes and expectation

Extrinsic tau-coupling and the regulation of interceptive reaching under varying task constraints

We investigated a general theory accounting for the guidance of ongoing movements in an interceptive reaching task. The aim was to assess the premise of tau-coupling that the coupling constant k, the ratio of taus(τs) of motion gaps between hand and object, reflects the kinematics of the on-going movement. The spatial and temporal constraints of the interceptive action were manipulated in three task conditions. While the time dependent counterpart of k, K(t) exhibited task effects, k itself could not distinguish between task manipulations. K(t) showed large variability during the initial acceleration phase, small variability during the rest of the movement, and task dependent changes during the final deceleration phase of interception. The findings highlight the importance of clarifying what constitutes as τ-coupling