BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage

BRCA1 is a major player in the DNA damage response. This is evident from its loss, which causes cells to become sensitive to a wide variety of DNA damaging agents. The major BRCA1 binding partner, BARD1, is also implicated in the DNA damage response, and recent reports indicate that BRCA1 and BARD1 co-operate in this pathway. In this report, we utilized small interfering RNA to deplete BRCA1 and BARD1 to demonstrate that the BRCA1-BARD1 complex is required for ATM/ATR (ataxia-telangiectasia-mutated/ATM and Rad3-related)-mediated phosphorylation of p53(Ser-15) following IR- and UV radiation-induced DNA damage. In contrast, phosphorylation of a number of other ATM/ATR targets including H2AX, Chk2, Chk1, and c-jun does not depend on the presence of BRCA1-BARD1 complexes. Moreover, prior ATM/ATR-dependent phosphorylation of BRCA1 at Ser-1423 or Ser-1524 regulates the ability of ATM/ATR to phosphorylate p53(Ser-15) efficiently. Phosphorylation of p53(Ser-15) is necessary for an IR-induced G(1)/S arrest via transcriptional induction of the cyclin-dependent kinase inhibitor p21. Consistent with these data, repressing p53(Ser-15) phosphorylation by BRCA1-BARD1 depletion compromises p21 induction and the G(1)/S checkpoint arrest in response to IR but not UV radia-tion. These findings suggest that BRCA1-BARD1 complexes act as an adaptor to mediate ATM/ATR-directed phosphorylation of p53, influencing G(1)/S cell cycle progression after DNA damage.

The contribution of N₂O₃ to the cytotoxicity of the nitric oxide donor DETA/NO: an emerging role for S-nitrosylation

The relationship between the biological activity of NO and its chemistry is complex. The objectives of this study were to investigate the influence of oxygen tension on the cytotoxicity of the NO• donor DETA/NO and to determine the effects of oxygen tension on the key RNS (reactive nitrogen species) responsible for any subsequent toxicity. The findings presented in this study indicate that the DETA/NO-mediated cytotoxic effects were enhanced under hypoxic conditions. Further investigations revealed that neither ONOO⁻ (peroxynitrite) nor nitroxyl was generated. Fluorimetric analysis in the presence of scavengers suggest for the first time that another RNS, dinitrogen trioxide may be responsible for the cytotoxicity with DETA/NO. Results showed destabilization of HIF (hypoxia inducible factor)-1α and depletion of GSH levels following the treatment with DETA/NO under hypoxia, which renders cells more susceptible to DETA/NO cytotoxicity, and could account for another mechanism of DETA/NO cytotoxicity under hypoxia. In addition, there was significant accumulation of nuclear p53, which showed that p53 itself might be a target for S-nitrosylation following the treatment with DETA/NO. Both the intrinsic apoptotic pathway and the Fas extrinsic apoptotic pathway were also activated. Finally, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is another important S-nitrosylated protein that may possibly play a key role in DETA/NO-mediated apoptosis and cytotoxicity. Therefore this study elucidates further mechanisms of DETA/NO mediated cytotoxicity with respect to S-nitrosylation that is emerging as a key player in the signalling and detection of DETA/NO-modified proteins in the tumour microenvironment.

Betwixt spaces: Students’ accounts of turning point experiences in first-year transitions

'Not belonging' is becoming a prevalent theme within accounts of the first-year student experience at university. In this study the notion of not belonging is extended by assuming a more active role for the idea of liminality in a student's transition into the university environments of academic and student life. In doing so, the article suggests that the transition between one place (home) and another (university) can result in an 'in-between-ness' - a betwixt space. Through an interpretative methodology, the study explores how students begin to move from this betwixt space into feeling like fully-fledged members of university life. It is concluded that there is a wide range of turning points associated with the students' betwixt transition, which shapes, alters or indeed accentuates the ways in which they make meaningful connections with university life. Moreover, transitional turning point experiences reveal a cast of characters and symbolic objects; capture contrasting motivations and evolving relationships; display multiple trajectories of interpersonal tensions and conflicts; highlight discontinuities as well as continuities; and together, simultaneously liberate and constrain the students' transition into university life.

IHG-1 must be localised to mitochondria to decrease Smad7 expression and amplify TGF-β1-induced fibrotic responses

TGF-ß1 is a prototypic profibrotic cytokine and major driver of fibrosis in the kidney and other organs. Induced in high glucose-1 (IHG-1) is a mitochondrial protein which we have recently reported to be associated with renal disease. IHG-1 amplifies responses to TGF-ß1 and regulates mitochondrial biogenesis by stabilising the transcriptional co-activator peroxisome proliferator-activated receptor gamma coactivator-1-alpha. Here we report that the mitochondrial localization of IHG-1 is pivotal in amplification of TGF-ß1 signaling. We demonstrate that IHG-1 expression is associated with repression of the endogenous TGF-ß1 inhibitor Smad7. Intriguingly, expression of a non-mitochondrial deletion mutant of IHG-1 (?mts-IHG-1) repressed TGF-ß1 fibrotic signaling in renal epithelial cells. In cells expressing ?mts-IHG-1 fibrotic responses including CCN2/connective tissue growth factor, fibronectin and jagged-1 expression were reduced following stimulation with TGF-ß1. ?mts-IHG-1 modulation of TGF-ß1 signaling was associated with increased Smad7 protein expression. ?mts-IHG-1 modulated TGF-ß1 activity by increasing Smad7 protein expression as it failed to inhibit TGF-ß1 transcriptional responses when endogenous Smad7 expression was knocked down. These data indicate that mitochondria modulate TGF-ß1 signal transduction and that IHG-1 is a key player in this modulation.

The Terror that Underpins the “Peace”: The Political Economy of Colombia's Paramilitary Demobilization Process

Studies on terrorism have traditionally focused on non-state actors who direct violence against liberal states. These studies also tend to focus on political motivations and, therefore, have neglected the economic functions of terrorism. This article challenges the divorce of the political and economic spheres by highlighting how states can use terrorism to realise interconnected political and economic goals. To demonstrate this, we take the case of the paramilitary demobilisation process in Colombia and show how it relates to the US-Colombian free trade agreement. We argue that the demobilisation process fulfils a dual role. First, the process aims to improve the image of the Colombian government required to pass the controversial free trade agreement through US Congress to protect large amounts of US investment in the country. Second, the demobilisation process serves to mask clear continuities in paramilitary terror that serve mutually supportive political and economic functions for US investment in Colombia.

Transnational Fantômas: The Influence of Feuillade’s Series on International Cinema during the 1910s

The influence of Fantômas novels and films on global popular culture is widely acknowledged. From the 1915 Spanish musical "Cine-fantomas" to the 1960s Italian comic book series "Diabolik," "Kriminal" and "Satanik," from Turkish B-movies such as "Fantoma Istanbulda Bulusalim" (dir. Natuk Baytan, 1967) to Julio Cortazar’s anti-imperialist pamphlet "Fantômas contra los vampiros multinacionales" (1975), Pierre Souvestre and Marcel Allain’s original literary series have engendered uncountable translations, adaptations, imitations and plagiarisms that have spread the character’s fame worldwide since its first appearance in 1911.
By focusing on the influence of Louis Feuillade’s film adaptations during the first decade of Fantômas’ long history as a transnational and transmedia icon, this paper aims to contribute to the growing interdisciplinary field that deals with the history of the supranational cultural sphere created by modern media culture. As a sort of archaeology of contemporary cultural globalization, this form of study intends to enrich previous historical surveys that had only taken into consideration specific national contexts. Moreover, it might also rebalance certain “colonizing” accounts that overemphasize the role of the cultural superpowers such as France, the UK or the US, often forgetting the appropriation of the products of international popular culture to be found in other countries. Therefore, this paper examines the transnational circulation of Fantômas films and, in particular, the creative processes engendered outside of France their origin country. As a controversial character and a central player in the relationship between cinema and literature in the crucial years when the feature and serial film boosted and legitimized the film industry, Fantômas represents an exemplary case study to discuss the cross-cultural and cross-media dynamics engendered by popular fiction.

Ion acceleration by superintense laser-plasma interaction

Ion acceleration driven by superintense laser pulses is attracting an impressive and steadily increasing effort. Motivations can be found in the applicative potential and in the perspective to investigate novel regimes as available laser intensities will be increasing. Experiments have demonstrated, over a wide range of laser and target parameters, the generation of multi-MeV proton and ion beams with unique properties such as ultrashort duration, high brilliance, and low emittance. An overview is given of the state of the art of ion acceleration by laser pulses as well as an outlook on its future development and perspectives. The main features observed in the experiments, the observed scaling with laser and plasma parameters, and the main models used both to interpret experimental data and to suggest new research directions are described.

Episodic Reasoning for Vision-Based Human Action Recognition

Smart Spaces, Ambient Intelligence, and Ambient Assisted Living are environmental paradigms that strongly depend on their capability to recognize human actions. While most solutions rest on sensor value interpretations and video analysis applications, few have realized the importance of incorporating common-sense capabilities to support the recognition process. Unfortunately, human action recognition cannot be successfully accomplished by only analyzing body postures. On the contrary, this task should be supported by profound knowledge of human agency nature and its tight connection to the reasons and motivations that explain it. The combination of this knowledge and the knowledge about how the world works is essential for recognizing and understanding human actions without committing common-senseless mistakes. This work demonstrates the impact that episodic reasoning has in improving the accuracy of a computer vision system for human action recognition. This work also presents formalization, implementation, and evaluation details of the knowledge model that supports the episodic reasoning.

A Hamiltonian approach to simulation of acoustic systems involving nonlinear interactions

Nonlinear interactions take place in most systems that arise in music acoustics, usually as a result of player-instrument coupling. Several time-stepping methods exist for the numerical simulation of such systems. These methods generally involve the discretization of the Newtonian description of the system. However, it is not always possible to prove the stability of the resulting algorithms, especially when dealing with systems where the underlying force is a non-analytic function of the phase space variables. On the other hand, if the discretization is carried out on the Hamiltonian description of the system, it is possible to prove the stability of the derived numerical schemes. This Hamiltonian approach is applied to a series of test models of single or multiple nonlinear collisions and the energetic properties of the derived schemes are discussed. After establishing that the schemes respect the principle of conservation of energy, a nonlinear single-reed model is formulated and coupled to a digital bore, in order to synthesize clarinet-like sounds.

Race, space and politics in Mid-Victorian Ireland: the ethnologies of Abraham Hume and John McElheran

There has been much scholarly debate about the significance and influence of racialist thinking in the political and cultural history of nineteenth-century Ireland. With reference to that ongoing historiographical discussion, this paper considers the racial geographies and opposing political motivations of two Irish ethnologists, Abraham Hume and John McElheran, using their racialist regimes to query some of the common assumptions that have informed disagreements over the role and reach of racial typecasting in mid-nineteenth-century Ireland. As well as examining in detail the racial imaginaries promulgated by Hume and McElheran, the paper also argues for the importance of situating racialist discourse in the spaces in which it was communicated and contested. Further, in highlighting the ways in which Hume and McElheran collapsed together race, class and religion, the paper troubles the utility of a crisp analytical distinction between those disputed categories.

Video Activism and the Ambiguities of Counter-Surveillance

This paper examines the use of visual technologies by political activists in protest situations to monitor police conduct. Using interview data with Australian video activists, this paper seeks to understand the motivations, techniques and outcomes of video activism, and its relationship to counter-surveillance and police accountability. Our data also indicated that there have been significant transformations in the organization and deployment of counter-surveillance methods since 2000, when there were large-scale protests against the World Economic Forum meeting in Melbourne accompanied by a coordinated campaign that sought to document police misconduct. The paper identifies and examines two inter-related aspects of this: the act of filming and the process of dissemination of this footage. It is noted that technological changes over the last decade have led to a proliferation of visual recording technologies, particularly mobile phone cameras, which have stimulated a corresponding proliferation of images. Analogous innovations in internet communications have stimulated a coterminous proliferation of potential outlets for images Video footage provides activists with a valuable tool for safety and publicity. Nevertheless, we argue, video activism can have unintended consequences, including exposure to legal risks and the amplification of official surveillance. Activists are also often unable to control the political effects of their footage or the purposes to which it is used. We conclude by assessing the impact that transformations in both protest organization and media technologies might have for counter-surveillance techniques based on visual surveillance.

Performer as perceiver: perceiver as performer

The proposition in the title of this paper is intended to draw a link between psychological processes involved in aesthetic gestural performance (e.g. music, dance) for both performers and perceivers. In the performance scenario, the player/dancer/etc., perceptually guides their actions, and acquires the skill for a performance through their previous perceptions. On the other side, the perceiver watching, listening to and experiencing another’s motor performance, simulates the actions of the performance within the range of their own motor capabilities. These phenomena are possible due to common mechanisms of action and perception, and in tandem provide the basis for the rich experience of gestural performance.
This paper reviews evidence for these claims, using examples from the domains of music and dance performance. Questions that arise from these propositions are addressed and suggested empirical explorations of these ideas are given. Further problems in incorporating these theories about gestural performance experience within Enaction are highlighted for future discussion.

An exploratory study of specialist and generalist teachers: predicting self efficacy in delivering primary physical education.

We aimed to determine whether primary school teachers’ motivational regulations to exercise and self efficacy in delivering a physical education (PE) lesson are different based on prior PE training. Two groups of qualified primary school teachers were recruited; PE specialists and a group of generalist primary school teachers who also teach PE. All teachers completed the Behavioural Regulation in Exercise Questionnaire-2, International Physical Activity Questionnaire and the Teachers’ Sense of Efficacy Scale. PE specialists demonstrated significantly higher levels of intrinsic motivation towards exercise participation and took part in more physical activity in comparison to the generalist teachers. Regression analysis showed that being a PE specialist predicted higher scores in instructional strategies and classroom management in PE. Our findings support the useof Self Determination Theory concepts in understanding teacher’s exercise participation motivations. These findings have implications for the modelling role of teachers in encouraging children to be physically active.

Unravelling the migration decision-making process: English early retirees moving to rural mid-Wales

There are established migrant reasons to explain rural in-migration. These include quality of life, rural idyll and lifestyle motivations. However, such one-dimensional sound bites portray rural in-migration in overly simplistic and stereotypical terms. In contrast, this paper distinguishes the decision to move from the reason for moving and in doing so sheds new light on the interconnections between different domains (family, work, finance, health) of the migrant's life which contribute to migration behaviour. Focussing on early retirees to mid-Wales and adopting a life course perspective the overall decision to move is disaggregated into a series of decisions. Giving voices to the migrants themselves demonstrates the combination of life events necessary to lead to migration behaviour, the variable factors (and often economic dominance) considered in the choice of destination (including that many are reluctant migrants to Wales), and the perceived 'accidental' choice of location and/or property. It is argued that quality of life, rural idyll and lifestyle sound bites offer an inadequate understanding of rural in-migration and associated decision-making processes. Moreover, they disguise the true nature of migrant decision making.

Gender Differences in the Perceptions of Genuine and Simulated Laughter and Amused Facial Expressions

This article addresses gender differences in laughter and smiling from an evolutionary perspective. Laughter and smiling can be responses to successful display behavior or signals of affiliation amongst conversational partners—differing social and evolutionary agendas mean there are different motivations when interpreting these signals. Two experiments assess perceptions of genuine
and simulated male and female laughter and amusement social signals. Results show male simulation can always be distinguished. Female simulation is more complicated as males seem to distinguish cues of simulation yet judge simulated signals to be genuine. Females judge other female’s genuine signals to have higher levels of simulation. Results highlight the importance of laughter and smiling in human interactions, use of dynamic stimuli, and using multiple methodologies to assess perception.