Double Dissociation of Amygdala and Hippocampal Contributions to Trace and Delay Fear Conditioning

A key finding in studies of the neurobiology of learning memory is that the amygdala is critically involved in Pavlovian fear conditioning. This is well established in delay-cued and contextual fear conditioning; however, surprisingly little is known of the role of the amygdala in trace conditioning. Trace fear conditioning, in which the CS and US are separated in time by a trace interval, requires the hippocampus and prefrontal cortex. It is possible that recruitment of cortical structures by trace conditioning alters the role of the amygdala compared to delay fear conditioning, where the CS and US overlap. To investigate this, we inactivated the amygdala of male C57BL/6 mice with GABA A agonist muscimol prior to 2-pairing trace or delay fear conditioning. Amygdala inactivation produced deficits in contextual and delay conditioning, but had no effect on trace conditioning. As controls, we demonstrate that dorsal hippocampal inactivation produced deficits in trace and contextual, but not delay fear conditioning. Further, pre- and post-training amygdala inactivation disrupted the contextual but the not cued component of trace conditioning, as did muscimol infusion prior to 1- or 4-pairing trace conditioning. These findings demonstrate that insertion of a temporal gap between the CS and US can generate amygdala-independent fear conditioning. We discuss the implications of this surprising finding for current models of the neural circuitry involved in fear conditioning

Balancing, Proportionality, and Constitutional Rights

In the theory and practice of constitutional adjudication, proportionality review plays a crucial role. At a theoretical level, it lies at core of the debate on rights adjudication; in judicial practice, it is a widespread decision-making model characterizing the action of constitutional, supra-national and international courts. Despite its circulation and centrality in contemporary legal discourse, proportionality in rights-adjudication is still extremely controversial. It raises normative questions—concerning its justification and limits—and descriptive questions—regarding its nature and distinctive features. The chapter addresses both orders of questions. Part I centres on the justification of proportionality review, the connection between proportionality, balancing and theories of rights and the critical aspects of this connection. Part II identifies and analyses the different forms of proportionality both in review, as a template for rights-adjudication, and of review, as a way of defining the scope and limits of adjudication

Predictors of binge drinking in adolescents: ultimate and distal factors - a representative study

<p>Abstract</p> <p>Background</p> <p>As epidemiological surveys have shown, binge drinking is a constant and wide-spread problem behavior in adolescents. It is not rare to find that more than half of all adolescents engage in this behavior when assessing only the last 4 weeks of time independent of the urbanity of the region they live in. There have been several reviews on predictors of substance consumption in adolescents in general, but there has been less high quality research on predictors of binge drinking, and most studies have not been theoretically based. The current study aimed to analyze the ultimate and distal factors predicting substance consumption according to Petraitis' theory of triadic influence. We assessed the predictive value of these factors with respect to binge drinking in German adolescents, including the identification of influence direction.</p> <p>Methods</p> <p>In the years 2007/2008, a representative written survey of N = 44,610 students in the 9^thgrade of different school types in Germany was carried out (net sample). The return rate of questionnaires was 88% regarding all students whose teachers or school directors had agreed to participate in the study. In this survey, prevalence of binge drinking was investigated as well as potential predictors from the social/interpersonal, the attitudinal/environmental, and the intrapersonal fields (3 factors of Petraitis). In a multivariate logistic regression analysis, these variables were included after testing for multicollinearity in order to assess their ability to predict binge drinking.</p> <p>Results</p> <p>Prevalence of binge drinking in the last 30 days was 52.3% for the surveyed adolescents with a higher prevalence for boys (56.9%) than for girls (47.5%). The two most influential factors found to protect against binge drinking with <it>p </it>< .001 were low economic status and importance of religion. The four most relevant risk factors for binge drinking (<it>p </it>< .001) were life-time prevalence of school absenteeism/truancy, academic failure, suicidal thoughts, and violence at school in the form of aggressive behavior of teachers. The model of Petraitis was partly confirmed for Binge Drinking in German adolescents and the direction of influence factors was clarified.</p> <p>Conclusions</p> <p>Whereas some of the risk and protective factors for binge drinking are not surprising since they are known for substance abuse in general, there are two points that could be targeted in interventions that do not focus on adolescents alone: (a) training teachers in positive, reassuring behavior and constructive criticism and (b) a focus on high risk adolescents either because they have a lack of coping strategies when in a negative mood or because of their low academic achievement in combination with absenteeism from school.</p

Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells

Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Sourcing Technological Knowledge Through Foreign Inward Licensing to Boost the Performance of Indian Firms: The Contingent Effects of Internal R&D and Business Group Affiliation

Sourcing technological knowledge from abroad is becoming a popular strategy among emerging market firms (EMFs). Combining the Knowledge-Based View and the Resource Dependence Theory, we argue that augmenting technological knowledge through foreign licensing enables EMFs to access state-of-the-art technological knowledge, reduce operational costs and risks associated to the innovation process, and develop a knowledge-based competitive advantage, ultimately boosting their financial performance. Using data about Indian firms observed from 2001 to 2013, we find that firms with a higher share of foreign inward technology licenses report better financial performance. However, the positive impact of technological knowledge accessed through inward licensing on firm performance is contingent upon: (1) the internal knowledge developed through R&D activity, and (2) the affiliation with business groups. While Indian firms with higher level of internal R&D are able to better leverage the value of foreign technological knowledge, thus reaching higher performance, firms affiliated to business groups gain fewer benefits from licensed foreign technological knowledge than non-business-group affiliated firms