The stem-loop binding protein regulates translation of histone mRNA during mammalian oogenesis

Although messenger RNAs encoding the histone proteins are among the most abundant in mammalian oocytes, the mechanism regulating their translation has not been identified. The stem-loop binding protein (SLBP) binds to a highly conserved sequence in the 3′-untranslated region (utr) of the non-polyadenylated histone mRNAs in somatic cells and mediates their stabilization and translation. We previously showed that SLBP, which is expressed only during S-phase of proliferating cells, is expressed in growing oocytes at G2 of the cell cycle and accumulates substantially during meiotic maturation. We report here that elevating the amount of SLBP in immature (G2) oocytes is sufficient to increase translation of a reporter mRNA bearing the histone 3′-utr and endogenous histone synthesis and that this effect is not mediated through increased stability of the encoding mRNAs. We further report that translation of the reporter mRNA increases dramatically during meiotic maturation coincident with the accumulation of SLBP. Conversely, when SLBP accumulation during maturation is prevented using RNA interference, both translation of the reporter mRNA and synthesis of endogenous histones are significantly reduced. This effect is not mediated by a loss of the encoding mRNAs. Moreover, following fertilization, SLBP-depleted oocytes also show a significant decrease in pronuclear size and in the amount of acetylated histone detectable on the chromatin. These results demonstrate that histone synthesis in immature and maturing oocytes is governed by a translational control mechanism that is directly regulated by changes in the amount of SLBP

tDCS increases anxiety reactivity to intentional worry

While considerable experimental research has examined the impact of transcranial direct current stimulation (tDCS) on a range of cognitive processes associated with emotional pathology, the impact of tDCS on worry has been comparatively neglected. Given that anxiety pathology is characterised by motivated engagement in worry, and that frontal tDCS has the capacity to enhance goal-oriented cognition, it is important to examine whether tDCS would increase or ameliorate the cognitive and emotional effects of worry. In the current study we examined how tDCS influenced the anxiety response to worry, and the frequency of negative intrusive thoughts. We additionally examined whether stimulation delivered in isolation, or in combination with a mindful-focus task would augment the effects of tDCS. Ninety-seven (75 female) healthy participants received either active or sham anodal tDCS to the left dorsolateral prefrontal cortex, delivered either in isolation or concurrently with a mindful task (four conditions). The frequency of negative thoughtc intrusions was assessed before and after a period of instructed worry, and state anxiety was assessed across the study. Active tDCS was associated with significantly greater elevation in anxiety in response to the worry induction. No effects were observed on the frequency of negative thought intrusions, and the combined delivery of tDCS with the concurrent mindful task did not alter the pattern of observed effects. While inviting replication in a high anxious sample, the present results highlight the possibility that tDCS may interact with motivated engagement in negative patterns of cognition, such as worry, to produce greater emotional reactivity

The effects of attentional bias modification on emotion regulation

BACKGROUND AND OBJECTIVES: In two experiments, we investigated the effects of Attentional Bias Modification (ABM) on emotion regulation, i.e. the manner in which people influence emotional experiences. We hypothesized that decreases in attentional bias to threat would impair upregulation and improve downregulation of negative emotions, while increases in attentional bias to threat would improve upregulation and impair downregulation of negative emotions. METHODS: Using the emotion-in-motion paradigm (Experiment 1, N = 60) and the visual search task (Experiment 2, N = 58), we trained participants to attend to either threatening or positive stimuli and we assessed emotion intensity while observing, upregulating, and downregulating emotions in response to grids of mixed emotional pictures. RESULTS: In Experiment 1, the attend positive group reported more positive emotions while merely watching grids of training pictures and the attend threat group showed impaired upregulation of negative affect. In Experiment 2, the attend threat group reported intensified negative emotions for all three instructions, while the attend positive group remained largely stable over time. LIMITATIONS: We cannot unequivocally attribute these changes in emotion regulation to changes in attentional bias, as neither of the experiments yielded significant changes in attentional bias to threat. CONCLUSIONS: By showing that attentional bias modification procedures affect the manner in which people deal with emotions, we add empirical weight to the conceptual overlap between attentional bias modification and emotion regulation

Chemical and Photometric Evolution of Extended Ultraviolet Disks: Optical Spectroscopy of M83 (NGC5236) and NGC4625

We present the results from the analysis of optical spectra of 31 Halpha-selected regions in the extended UV (XUV) disks of M83 (NGC5236) and NGC4625 recently discovered by GALEX. The spectra were obtained using IMACS at Las Campanas Observatory 6.5m Magellan I telescope and COSMIC at the Palomar 200-inch telescope, respectively for M83 and NGC4625. The line ratios measured indicate nebular oxygen abundances (derived from the R23 parameter) of the order of Zsun/5-Zsun/10. For most emission-line regions analyzed the line fluxes and ratios measured are best reproduced by models of photoionization by single stars with masses in the range 20-40 Msun and oxygen abundances comparable to those derived from the R23 parameter. We find indications for a relatively high N/O abundance ratio in the XUV disk of M83. Although the metallicities derived imply that these are not the first stars formed in the XUV disks, such a level of enrichment could be reached in young spiral disks only 1 Gyr after these first stars would have formed. The amount of gas in the XUV disks allow maintaining the current level of star formation for at least a few Gyr.Comment: 52 pages, 8 tables, 7 figures, accepted for publication in Ap

Leading-effect vs. Risk-taking in Dynamic Tournaments: Evidence from a Real-life Randomized Experiment

Two 'order effects' may emerge in dynamic tournaments with information feedback. First, participants adjust effort across stages, which could advantage the leading participant who faces a larger 'effective prize' after an initial victory (leading-effect). Second, participants lagging behind may increase risk at the final stage as they have 'nothing to lose' (risk-taking). We use a randomized natural experiment in professional two-game soccer tournaments where the treatment (order of a stage-specific advantage) and team characteristics, e.g. ability, are independent. We develop an identification strategy to test for leading-effects controlling for risk-taking. We find no evidence of leading-effects and negligible risk-taking effects

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Reinventing grounded theory: some questions about theory, ground and discovery

Grounded theory’s popularity persists after three decades of broad-ranging critique. In this article three problematic notions are discussed—‘theory,’ ‘ground’ and ‘discovery’—which linger in the continuing use and development of grounded theory procedures. It is argued that far from providing the epistemic security promised by grounded theory, these notions—embodied in continuing reinventions of grounded theory—constrain and distort qualitative inquiry, and that what is contrived is not in fact theory in any meaningful sense, that ‘ground’ is a misnomer when talking about interpretation and that what ultimately materializes following grounded theory procedures is less like discovery and more akin to invention. The procedures admittedly provide signposts for qualitative inquirers, but educational researchers should be wary, for the significance of interpretation, narrative and reflection can be undermined in the procedures of grounded theory

Genetic stratification of depression in UK Biobank

Depression is a common and clinically heterogeneous mental health disorder that is frequently comorbid with other diseases and conditions. Stratification of depression may align sub-diagnoses more closely with their underling aetiology and provide more tractable targets for research and effective treatment. In the current study, we investigated whether genetic data could be used to identify subgroups within people with depression using the UK Biobank. Examination of cross-locus correlations were used to test for evidence of subgroups using genetic data from seven other complex traits and disorders that were genetically correlated with depression and had sufficient power (>0.6) for detection. We found no evidence for subgroups within depression for schizophrenia, bipolar disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, anorexia nervosa, inflammatory bowel disease or obesity. This suggests that for these traits, genetic correlations with depression were driven by pleiotropic genetic variants carried by everyone rather than by a specific subgroup

Search for Yukawa Production of a Light Neutral Higgs Boson at LEP

Within a Two-Higgs-Doublet Model (2HDM) a search for a light Higgs boson in the mass range of 4-12 GeV has been performed in the Yukawa process e+e- -> b bbar A/h -> b bbar tau+tau-, using the data collected by the OPAL detector at LEP between 1992 and 1995 in e+e- collisions at about 91 GeV centre-of-mass energy. A likelihood selection is applied to separate background and signal. The number of observed events is in good agreement with the expected background. Within a CP-conserving 2HDM type II model the cross-section for Yukawa production depends on xiAd = |tan beta| and xihd = |sin alpha/cos beta| for the production of the CP-odd A and the CP-even h, respectively, where tan beta is the ratio of the vacuum expectation values of the Higgs doublets and alpha is the mixing angle between the neutral CP-even Higgs bosons. From our data 95% C.L. upper limits are derived for xiAd within the range of 8.5 to 13.6 and for xihd between 8.2 to 13.7, depending on the mass of the Higgs boson, assuming a branching fraction into tau+tau- of 100%. An interpretation of the limits within a 2HDM type II model with Standard Model particle content is given. These results impose constraints on several models that have been proposed to explain the recent BNL measurement of the muon anomalous magnetic moment.Comment: 24 pages, 9 figures, Submitted to Euro. Phys. J.