Psychopathy and the DSM-IV criteria for antisocial personality disorder.

The Axis II Work Group of the Task Force on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) has expressed concern that antisocial personality disorder (APD) criteria are too long and cumbersome and that they focus on antisocial behaviors rather than personality traits central to traditional conceptions of psychopathy and to international criteria. R. D. Hare et al describe an alternative to the approach taken in the DSM-III—Revised (DSM-III—R; American Psychiatric Association, 1987), namely, the revised Psychopathy Checklist. The authors also discuss the multisite APD field trials designed to evaluate and compare 4 criteria sets: the DSM-III—R criteria, a shortened list of these criteria, the criteria for dyssocial personality disorder from the 10th edition of the International Classification of Diseases (World Health Organization, 1990), and a 10-item criteria set for psychopathic personality disorder derived from the revised Psychopathy Checklist. (PsycINFO Database Record (c) 2015 APA, all rights reserved

Some Secrets of Fluorescent Proteins: Distinct Bleaching in Various Mounting Fluids and Photoactivation of cyan fluorescent proteins at YFP-Excitation

Background
The use of spectrally distinct variants of green fluorescent protein (GFP) such as cyan or yellow mutants (CFP and YFP, respectively) is very common in all different fields of life sciences, e.g. for marking specific proteins or cells or to determine protein interactions. In the latter case, the quantum physical phenomenon of fluorescence resonance energy transfer (FRET) is exploited by specific microscopy techniques to visualize proximity of proteins.

Methodology/Principal Findings
When we applied a commonly used FRET microscopy technique - the increase in donor (CFP)-fluorescence after bleaching of acceptor fluorophores (YFP), we obtained good signals in live cells, but very weak signals for the same samples after fixation and mounting in commercial microscopy mounting fluids. This observation could be traced back to much faster bleaching of CFP in these mounting media. Strikingly, the opposite effect of the mounting fluid was observed for YFP and also for other proteins such as Cerulean, TFP or Venus. The changes in photostability of CFP and YFP were not caused by the fixation but directly dependent on the mounting fluid. Furthermore we made the interesting observation that the CFP-fluorescence intensity increases by about 10 - 15% after illumination at the YFP-excitation wavelength – a phenomenon, which was also observed for Cerulean. This photoactivation of cyan fluorescent proteins at the YFP-excitation can cause false-positive signals in the FRET-microscopy technique that is based on bleaching of a yellow FRET acceptor.

Conclusions/Significance
Our results show that photostability of fluorescent proteins differs significantly for various media and that CFP bleaches significantly faster in commercial mounting fluids, while the opposite is observed for YFP and some other proteins. Moreover, we show that the FRET microscopy technique that is based on bleaching of the YFP is prone to artifacts due to photoactivation of cyan fluorescent proteins under these conditions

Institutional Mergers in Ireland

The importance of knowledge as a driver of social and economic growth and prosperity, and the increasingly competitive “global race for knowledge and talent” (Hazelkorn, Higher Educ Manage Policy 21(1):55–76, 2009) have combined to transform the higher education landscape, forcing national governments and higher education institutions (HEIs) to pursue new ways of addressing the challenges of a multi-polar world order. Rising demand for higher education (HE), as part of the broader shift from elite to mass to universal participation, has led to the emergence of new models of provision. At the same time, many governments face restrictions on public resources due to high levels of public and private debt; accordingly, system-level and institutional restructuring has been contemplated as a way to enhance quality, performance and efficiency

The Development of Inclusive Learning Relationships in Mainstream Settings: A Multimodal Perspective

The debate regarding the inclusion of children with Special Educational Needs and Disabilities (SEND) in mainstream education in the UK partly revolves around what makes the classroom environment inclusive. Through the potential offered by the specific qualitative methodologies employed, this study aimed to explore the development of teachers’ pedagogical practices and learning relationships upon the inclusive education of children with special educational needs and disabilities in two primary school classes. The study considered the views and behaviours of primary school pupils with and without special educational needs, primary school teachers and teaching assistants (TAs) in one mainstream school. Drawing on a multimodal approach to discourse analysis to account for the complex relationships between symbolic and non-verbal modes of classroom signification, the study explored how meaning is produced in classrooms and children’s modes of communication, as well as in teachers’ practices. The two classes are compared on the basis of teaching observations, interviews, transcripts of dialogues, and analyses of classroom organisation and decoration. This paper suggests that the greatest influence on the educational and social outcomes of students with special educational needs is the behaviour and practices of the classroom teacher

Sensitive Detection of p65 Homodimers Using Red-Shifted and Fluorescent Protein-Based FRET Couples

BACKGROUND: Fluorescence Resonance Energy Transfer (FRET) between the green fluorescent protein (GFP) variants CFP and YFP is widely used for the detection of protein-protein interactions. Nowadays, several monomeric red-shifted fluorescent proteins are available that potentially improve the efficiency of FRET. METHODOLOGY/PRINCIPAL FINDINGS: To allow side-by-side comparison of several fluorescent protein combinations for detection of FRET, yellow or orange fluorescent proteins were directly fused to red fluorescent proteins. FRET from yellow fluorescent proteins to red fluorescent proteins was detected by both FLIM and donor dequenching upon acceptor photobleaching, showing that mCherry and mStrawberry were more efficient acceptors than mRFP1. Circular permutated yellow fluorescent protein variants revealed that in the tandem constructs the orientation of the transition dipole moment influences the FRET efficiency. In addition, it was demonstrated that the orange fluorescent proteins mKO and mOrange are both suitable as donor for FRET studies. The most favorable orange-red FRET pair was mKO-mCherry, which was used to detect homodimerization of the NF-kappaB subunit p65 in single living cells, with a threefold higher lifetime contrast and a twofold higher FRET efficiency than for CFP-YFP. CONCLUSIONS/SIGNIFICANCE: The observed high FRET efficiency of red-shifted couples is in accordance with increased Förster radii of up to 64 A, being significantly higher than the Förster radius of the commonly used CFP-YFP pair. Thus, red-shifted FRET pairs are preferable for detecting protein-protein interactions by donor-based FRET methods in single living cells

Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation

The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85α mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85α mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85α towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85α BH domain mutants (E137K, E217K, R262T E297K) for bovine p85α BH and found that the mutations did not alter the overall domain structure. Thus, several p85α mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85α BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activit

Before and after study of bar workers' perceptions of the impact of smoke-free workplace legislation in the Republic of Ireland

<p>Abstract</p> <p>Background</p> <p><it>Objectives</it>: To compare support for, and perceptions of, the impacts of smoke-free workplace legislation among bar workers in the Republic of Ireland (ROI) pre- and post-implementation, and to identify predictors of support for the legislation.</p> <p>Methods</p> <p><it>Setting</it>: Public houses (pubs) in three areas of the ROI.</p> <p><it>Design</it>: Comparisons pre- and post-implementation of smoke-free workplace legislation.</p> <p><it>Participants</it>: From a largely non-random selection, 288 bar workers volunteered for the baseline survey; 220 were followed up one year later (76.4%).</p> <p><it>Outcome measures: </it>Level of support for the legislation, attitude statements concerning potential impacts of the law and modelled predictors of support for the legislation.</p> <p>Results</p> <p>Pre-implementation 59.5% of participants supported the legislation, increasing to 76.8% post-implementation. Support increased among smokers by 27.3 percentage points from 39.4% to 66.7% (p < 0.001) and among non-smokers by 12.4% percentage points from 68.8% to 81.2% (p = 0.003).</p> <p>Pre-legislation three-quarters of participants agreed that the legislation would make bars more comfortable and was needed to protect workers' health. Post-legislation these proportions increased to over 90% (p < 0.001). However, negative perceptions also increased, particularly for perceptions that the legislation has a negative impact on business (from 50.9% to 62.7%, p = 0.008) and that fewer people would visit pubs (41.8% to 62.7%, p < 0.001). After adjusting for relevant covariates, including responses to the attitude statements, support for the ban increased two to three-fold post-implementation. Regardless of their views on the economic impact, most participants agreed, both pre- and post-implementation, that the legislation was needed to protect bar workers' health.</p> <p>Conclusion</p> <p>Smoke-free legislation had the support of three-quarters of a large sample of bar workers in the ROI. However, this group holds complex sets of both positive and negative perspectives on the legislation. Of particular importance is that negative economic perceptions did not diminish the widely held perception that the ban is needed to protect workers' health.</p

The Janus kinases (Jaks)

The Janus kinase (Jak) family is one of ten recognized families of non-receptor tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and they each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin, radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are activated and phosphorylate the receptors, creating docking sites for signaling molecules, especially members of the signal transducer and activator of transcription (Stat) family. Mutations of the Drosophila Jak (Hopscotch) have revealed developmental defects, and constitutive activation of Jaks in flies and humans is associated with leukemia-like syndromes. Through the generation of Jak-deficient cell lines and gene-targeted mice, the essential, nonredundant functions of Jaks in cytokine signaling have been established. Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs

Gadolinium and nephrogenic systemic fibrosis: time to tighten practice

Nephrogenic systemic fibrosis (NSF) is a relatively new entity, first described in 1997. Few cases have been reported, but the disease has high morbidity and mortality. To date it has been seen exclusively in patients with renal dysfunction. There is an emerging link with intravenous injection of gadolinium contrast agents, which has been suggested as a main triggering factor, with a lag time of days to weeks. Risk factors include the severity of renal impairment, major surgery, vascular events and other proinflammatory conditions. There is no reason to believe that children have an altered risk compared to the adult population. It is important that the paediatric radiologist acknowledges emerging information on NSF but at the same time considers the risk:benefit ratio prior to embarking on alternative investigations, as children with chronic kidney disease require high-quality diagnostic imaging