Psychometric and Experimental Investigations of Beliefs About Losing Control

According to cognitive theory, maladaptive beliefs play a pivotal role in the development and maintenance of anxiety-related problems and there is overlap in the beliefs involved across these disorders. Interestingly, clinical reports claim that individuals with obsessive-compulsive disorder (OCD) and with social anxiety disorder (SAD) fear losing control over their thoughts, behaviour, emotions, and/or bodily functions. This indicates that negative beliefs about the likelihood and consequences of losing control could be involved in both disorders. This program of research was designed to foster psychometric investigations of beliefs about losing control and increase our understanding of the causal role of these beliefs in OCD and SAD. In Study 1, a measure of maladaptive beliefs about losing control, the Beliefs About Losing Control Inventory (BALCI), was validated in a sample of undergraduate students (N = 488). Results indicated that the BALCI’s items capture beliefs about losing control over one’s thoughts/behaviour/emotions (Factor 1), about the importance of staying in control (Factor 2), and about losing control over one’s body/bodily functions (Factor 3). The BALCI was found to be psychometrically sound and associated with OCD symptoms above and beyond already established maladaptive beliefs. In Study 2, beliefs about the likelihood of losing control over one’s behaviour were manipulated by providing false feedback to undergraduate participants (N = 128). Believing that one is likely to lose control over their behaviour led to increasing anxiety while approaching stimuli that are typically feared in OCD, lower perceived caution while interacting with these stimuli, and recalling experiencing more unwanted intrusions throughout the protocol. In Study 3, beliefs about the likelihood and consequences of losing control over one’s actions/speech were manipulated by assigning undergraduate participants (N = 93) to drinking vodka (alcohol condition), alcohol-free vodka (placebo condition), or orange juice (control condition). Participants then interacted with a stranger. Results indicated that those in the placebo (versus control) condition experienced greater anxiety, perceived themselves as making a poorer first impression, and reported engaging in more post-event processing. The pharmacological effects of alcohol appeared to mitigate the effects of beliefs about losing control. Implications for cognitive-behavioural theories and therapies are discussed

An experimental approach to understanding beliefs about losing control in obsessive-compulsive disorder

Cognitive theories of obsessive-compulsive disorder (OCD) posit that maladaptive beliefs lead to the development and maintenance of symptoms. However, currently identified beliefs (about responsibility and threat overestimation, perfectionism and intolerance for uncertainty, and about the importance of and control over thoughts) do not sufficiently explain OCD symptomatology. Anecdotal and other reports have documented concerns among those diagnosed with OCD regarding a potential loss of control over their thoughts and behaviour, indicating that negative beliefs about losing control may be an important cognitive domain involved in the aetiology of OCD. In this study, 133 undergraduate participants received (positive or negative) false feedback about their capacity to stay in control during a bogus EEG session, and completed a computer task asking them to control the pace of a series of pictures. As hypothesized, participants provided with negative feedback about their capacity to stay in control (i.e., high negative beliefs about losing control) checked significantly more often which keys they should use to control the pictures, t(106.95) = 2.28, p = .02, d = .44, as compared to participants provided with positive feedback (i.e., low negative beliefs about losing control), demonstrating that manipulating beliefs about losing control can impact checking behaviour. Also, checking behaviour predicted a lower desire for control over the computer task’s pictures, r(131) = -.30, p < .001, such that compulsions may be seen as opportunities to re-establish disrupted perceptions of control. Results support the inclusion of beliefs about losing control in cognitive models of OCD

Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Poly(ADP-ribose) polymerases (PARPs) catalyze the formation of poly(ADP-ribose) (pADPr), a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose) glycohydrolase (PARG), on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosyl)ation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS) aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions.</p> <p>Results</p> <p>PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1.</p> <p>Conclusions</p> <p>This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose) metabolism.</p

Creation of backdoors in quantum communications via laser damage

Practical quantum communication (QC) protocols are assumed to be secure provided implemented devices are properly characterized and all known side channels are closed. We show that this is not always true. We demonstrate a laser-damage attack capable of modifying device behaviour on-demand. We test it on two practical QC systems for key distribution and coin-tossing, and show that newly created deviations lead to side channels. This reveals that laser damage is a potential security risk to existing QC systems, and necessitates their testing to guarantee security.Comment: Changed the title to match the journal version. 9 pages, 5 figure

Proteomics reveals a switch in CDK1-associated proteins upon M-phase exit during the Xenopus laevis oocyte to embryo transition.

International audienceCyclin-dependent kinase 1 (CDK1) is a major M-phase kinase which requires the binding to a regulatory protein, Cyclin B, to be active. CDK1/Cyclin B complex is called M-phase promoting factor (MPF) for its key role in controlling both meiotic and mitotic M-phase of the cell cycle. CDK1 inactivation is necessary for oocyte activation and initiation of embryo development. This complex process requires both Cyclin B polyubiquitination and proteosomal degradation via the ubiquitin-conjugation pathway, followed by the dephosphorylation of the monomeric CDK1 on Thr161. Previous proteomic analyses revealed a number of CDK1-associated proteins in human HeLa cells. It is, however, unknown whether specific partners are involved in CDK1 inactivation upon M-phase exit. To better understand CDK1 regulation during MII-arrest and oocyte activation, we immunoprecipitated (IPed) CDK1 together with its associated proteins from M-phase-arrested and M-phase-exiting Xenopus laevis oocytes. A mass spectrometry (MS) analysis revealed a number of new putative CDK1 partners. Most importantly, the composition of the CDK1-associated complex changed rapidly during M-phase exit. Additionally, an analysis of CDK1 complexes precipitated with beads covered with p9 protein, a fission yeast suc1 homologue well known for its high affinity for CDKs, was performed to identify the most abundant proteins associated with CDK1. The screen was auto-validated by identification of: (i) two forms of CDK1: Cdc2A and B, (ii) a set of Cyclins B with clearly diminishing number of peptides identified upon M-phase exit, (iii) a number of known CDK1 substrates (e.g. peroxiredoxine) and partners (e.g. HSPA8, a member of the HSP70 family) both in IP and in p9 precipitated pellets. In IP samples we also identified chaperones, which can modulate CDK1 three-dimensional structure, as well as calcineurin, a protein necessary for successful oocyte activation. These results shed a new light on CDK1 regulation via a dynamic change in the composition of the protein complex upon M-phase exit and the oocyte to embryo transition

Comparative proteome analysis of human epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Epithelial ovarian cancer is a devastating disease associated with low survival prognosis mainly because of the lack of early detection markers and the asymptomatic nature of the cancer until late stage. Using two complementary proteomics approaches, a differential protein expression profile was carried out between low and highly transformed epithelial ovarian cancer cell lines which realistically mimic the phenotypic changes observed during evolution of a tumour metastasis. This investigation was aimed at a better understanding of the molecular mechanisms underlying differentiation, proliferation and neoplastic progression of ovarian cancer.</p> <p>Results</p> <p>The quantitative profiling of epithelial ovarian cancer model cell lines TOV-81D and TOV-112D generated using iTRAQ analysis and two-dimensional electrophoresis coupled to liquid chromatography tandem mass spectrometry revealed some proteins with altered expression levels. Several of these proteins have been the object of interest in cancer research but others were unrecognized as differentially expressed in a context of ovarian cancer. Among these, series of proteins involved in transcriptional activity, cellular metabolism, cell adhesion or motility and cytoskeleton organization were identified, suggesting their possible role in the emergence of oncogenic pathways leading to aggressive cellular behavior.</p> <p>Conclusion</p> <p>The differential protein expression profile generated by the two proteomics approaches combined to complementary characterizations studies will open the way to more exhaustive and systematic representation of the disease and will provide valuable information that may be helpful to uncover the molecular mechanisms related to epithelial ovarian cancer.</p

Open multistate Majorana model

The multistate Majorana model in the presence of dissipation and dephasing is considered. It is proven that increasing the Hilbert space dimension the system becomes more and more fragile to quantum noise. The impossibility to recast the problem in the form of a set of independent spin-$1/2$ problems because of the presence of the noise is pointed out

Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells.

International audienceThe mitotic spindle is crucial to achieve segregation of sister chromatids. To identify new mitotic spindle assembly regulators, we isolated 855 microtubule-associated proteins (MAPs) from Drosophila melanogaster mitotic or interphasic embryos. Using RNAi, we screened 96 poorly characterized genes in the Drosophila central nervous system to establish their possible role during spindle assembly. We found that Ensconsin/MAP7 mutant neuroblasts display shorter metaphase spindles, a defect caused by a reduced microtubule polymerization rate and enhanced by centrosome ablation. In agreement with a direct effect in regulating spindle length, Ensconsin overexpression triggered an increase in spindle length in S2 cells, whereas purified Ensconsin stimulated microtubule polymerization in vitro. Interestingly, ensc-null mutant flies also display defective centrosome separation and positioning during interphase, a phenotype also detected in kinesin-1 mutants. Collectively, our results suggest that Ensconsin cooperates with its binding partner Kinesin-1 during interphase to trigger centrosome separation. In addition, Ensconsin promotes microtubule polymerization during mitosis to control spindle length independent of Kinesin-1

CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage

Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins, including CBX4, have been shown to accumulate at sites of DNA damage. However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity is directly involved in the DNA damage response (DDR). Here we define a novel role for CBX4 as an early DDR protein that mediates SUMO conjugation at sites of DNA lesions. DNA damage stimulates sumoylation of BMI1 by CBX4 at lysine 88, which is required for the accumulation of BMI1 at DNA damage sites. Moreover, we establish that CBX4 recruitment to the sites of laser micro-irradiation-induced DNA damage requires PARP activity but does not require H2AX, RNF8, BMI1 nor PI-3-related kinases. The importance of CBX4 in the DDR was confirmed by the depletion of CBX4, which resulted in decreased cellular resistance to ionizing radiation. Our results reveal a direct role for CBX4 in the DDR pathway

Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes

Poly(ADP-ribose) (pADPr) is a polymer assembled from the enzymatic polymerization of the ADP-ribosyl moiety of NAD by poly(ADP-ribose) polymerases (PARPs). The dynamic turnover of pADPr within the cell is essential for a number of cellular processes including progression through the cell cycle, DNA repair and the maintenance of genomic integrity, and apoptosis. In spite of the considerable advances in the knowledge of the physiological conditions modulated by poly(ADP-ribosyl)ation reactions, and notwithstanding the fact that pADPr can play a role of mediator in a wide spectrum of biological processes, few pADPr binding proteins have been identified so far. In this study, refined in silico prediction of pADPr binding proteins and large-scale mass spectrometry-based proteome analysis of pADPr binding proteins were used to establish a comprehensive repertoire of pADPr-associated proteins. Visualization and modeling of these pADPr-associated proteins in networks not only reflect the widespread involvement of poly(ADP-ribosyl)ation in several pathways but also identify protein targets that could shed new light on the regulatory functions of pADPr in normal physiological conditions as well as after exposure to genotoxic stimuli