An Increase in Tobacco Craving Is Associated with Enhanced Medial Prefrontal Cortex Network Coupling

Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI) in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC) network, which also included the subgenual anterior cingulate cortex (sgACC) extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving

The representation of scientific research in the national curriculum and secondary school pupils’ perceptions of research, its function, usefulness and value to their lives

Young people’s views on what research is, how it is conducted and whether it is important, influences the decisions they make about their further studies and career choices. In this paper we report the analysis of questionnaire data with a particular focus on pupil perceptions of research in the sciences and of the scientific method. The questionnaire was a 25-item Likert Scale (1-5) distributed to seven collaborating schools. We received 2634 returns from pupils across key stages 3, 4 and 5. We also asked teachers to complete the questionnaire in order to explore how they thought their pupils would respond. We received 54 teacher responses. Statistically significant differences in the responses were identified through a chi-square test on SPSS. As what is being taught influences secondary pupil views on research we also consider how the term ‘research’ appears in the national curriculum for England and Wales and the three main English exam boards. The main theoretical construct that informs our analysis of the questionnaire data and the national curriculum is Angela Brew’s 4-tier descriptor of perceptions of research (domino, trading, layer, journey). We use this framework in order to map what, when and how research is presented to school pupils in England and Wales. We also use this framework in order to highlight and discuss certain pupil views that emerged from the questionnaire data and which indicate areas where curriculum and pedagogy intervention may be necessary: pupils seem less confident in their understanding of research as involving the identification of a research question; and, they often see research as a means to confirm one’s own opinion. They do however understand research as involving the generation of new knowledge and the collection of new data, such as interviews and questionnaires as well as laboratory work, field trips and library searches and they appear relatively confident in their statements about their ability to do research, their school experiences of research and the importance of research in their future career choice

Sortilin regulates sorting and secretion of Sonic hedgehog

Sonic Hedgehog (Shh) is a secreted morphogen that is an essential regulator of patterning and growth. The Shh full-length protein undergoes autocleavage in the ER to generate the biologically active amino-terminal ShhN fragment, which is destined for secretion. Few receptors have been identified that control the trafficking of this morphogen through the secretory pathway. We identified Sortilin (Sort1), a member of the VPS10P domain receptor family, as a novel Shh trafficking receptor. We demonstrate that Sort/Shh interact using co-IP and proximity ligation in transfected cells and that they co-localize to the Golgi. Sort1 overexpression causes re-distribution of ShhN, and to a lesser extent ShhFL, to the Golgi and reduces Shh secretion. We show loss of Sort1 can partially rescue Hedgehog-associated patterning defects in a mouse model of deficient Shh processing and that Sort1 levels negatively regulate anterograde Shh transport in axons in vitro and Hh-dependent axon-glial interactions in vivo Taken together, we conclude that Shh and Sort1 can interact at the level of the Golgi and that Sort1 directs Shh away from the pathways that promote its secretion

Farnesol restores wild-type colony morphology to 96% of \u3ci\u3eCandida albicans\u3c/i\u3e colony morphology variants recovered following treatment with mutagens

Candida albicans is a diploid fungus that undergoes a morphological transition between budding yeast, hyphal, and pseudohyphal forms. The morphological transition is strongly correlated with virulence and is regulated in part by quorum sensing. Candida albicans produces and secretes farnesol that regulates the yeast to mycelia morphological transition. Mutants that fail to synthesize or respond to farnesol could be locked in the filamentous mode. To test this hypothesis, a collection of C. albicans mutants were isolated that have altered colony morphologies indicative of the presence of hyphal cells under environmental conditions where C. albicans normally grows only as yeasts. All mutants were characterized for their ability to respond to farnesol. Of these, 95.9% fully or partially reverted to wildtype morphology on yeast malt (YM) agar plates supplemented with farnesol. All mutants that respond to farnesol regained their hyphal morphology when restreaked on YM plates without farnesol. The observation that farnesol remedial mutants are so common (95.9%) relative to mutants that fail to respond to farnesol (4.1%) suggests that farnesol activates and (or) induces a pathway that can override many of the morphogenesis defects in these mutants. Additionally, 9 mutants chosen at random were screened for farnesol production. Two mutants failed to produce detectable levels of farnesol. Candida albicans est un champignon diploïde qui subit une transition morphologique entre les levures en herbe, les hyphes et les formes pseudohyphales. La transition morphologique est fortement corrélée à la virulence et est régulée en partie par la détection du quorum. Candida albicans produit et sécrète du farnésol qui régule la transition morphologique levure-mycélium. Les mutants qui ne parviennent pas à synthétiser ou à répondre au farnésol pourraient être verrouillés en mode filamenteux. Pour tester cette hypothèse, une collection de mutants de C. albicans a été isolée qui ont modifié les morphologies des colonies, indiquant la présence de cellules hyphales dans des conditions environnementales où C. albicans ne pousse normalement que sous forme de levures. Tous les mutants ont été caractérisés pour leur capacité à répondre au farnésol. Parmi ceux-ci, 95,9% sont entièrement ou partiellement revenus à la morphologie de type sauvage sur des plaques de gélose au levure de malt (YM) complétées par du farnésol. Tous les mutants qui répondent au farnésol ont retrouvé leur morphologie hyphale lorsqu\u27ils ont été recréés sur des plaques YM sans farnésol. L\u27observation selon laquelle les mutants curatifs du farnésol sont si communs (95,9%) par rapport aux mutants qui ne répondent pas au farnésol (4,1%) suggère que le farnésol s\u27active et (ou) induit une voie qui peut supplanter bon nombre des défauts de morphogenèse de ces mutants. De plus, 9 mutants choisis au hasard ont été testés pour la production de farnésol. Deux mutants n\u27ont pas réussi à produire des niveaux détectables de farnésol

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

Detection of Potential Transit Signals in the First Three Quarters of Kepler Mission Data

We present the results of a search for potential transit signals in the first three quarters of photometry data acquired by the Kepler Mission. The targets of the search include 151,722 stars which were observed over the full interval and an additional 19,132 stars which were observed for only 1 or 2 quarters. From this set of targets we find a total of 5,392 detections which meet the Kepler detection criteria: those criteria are periodicity of the signal, an acceptable signal-to-noise ratio, and a composition test which rejects spurious detections which contain non-physical combinations of events. The detected signals are dominated by events with relatively low signal-to-noise ratio and by events with relatively short periods. The distribution of estimated transit depths appears to peak in the range between 40 and 100 parts per million, with a few detections down to fewer than 10 parts per million. The detected signals are compared to a set of known transit events in the Kepler field of view which were derived by a different method using a longer data interval; the comparison shows that the current search correctly identified 88.1% of the known events. A tabulation of the detected transit signals, examples which illustrate the analysis and detection process, a discussion of future plans and open, potentially fruitful, areas of further research are included

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection

The Generic Genome Browser: A building block for a model organism system database

The Generic Model Organism System Database Project (GMOD) seeks to develop reusable software components for model organism system databases. In this paper we describe the Generic Genome Browser (GBrowse), a Web-based application for displaying genomic annotations and other features. For the end user, features of the browser include the ability to scroll and zoom through arbitrary regions of a genome, to enter a region of the genome by searching for a landmark or performing a full text search of all features, and the ability to enable and disable tracks and change their relative order and appearance. The user can upload private annotations to view them in the context of the public ones, and publish those annotations to the community. For the data provider, features of the browser software include reliance on readily available open source components, simple installation, flexible configuration, and easy integration with other components of a model organism system Web site. GBrowse is freely available under an open source license. The software, its documentation, and support are available at http://www.gmod.org