Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat

Quantum control of hybrid nuclear-electronic qubits

Pulsed magnetic resonance is a wide-reaching technology allowing the quantum state of electronic and nuclear spins to be controlled on the timescale of nanoseconds and microseconds respectively. The time required to flip either dilute electronic or nuclear spins is orders of magnitude shorter than their decoherence times, leading to several schemes for quantum information processing with spin qubits. We investigate instead the novel regime where the eigenstates approximate 50:50 superpositions of the electronic and nuclear spin states forming "hybrid nuclear-electronic" qubits. Here we demonstrate quantum control of these states for the first time, using bismuth-doped silicon, in just 32 ns: this is orders of magnitude faster than previous experiments where pure nuclear states were used. The coherence times of our states are five orders of magnitude longer, reaching 4 ms, and are limited by the naturally-occurring 29Si nuclear spin impurities. There is quantitative agreement between our experiments and no-free-parameter analytical theory for the resonance positions, as well as their relative intensities and relative Rabi oscillation frequencies. In experiments where the slow manipulation of some of the qubits is the rate limiting step, quantum computations would benefit from faster operation in the hybrid regime.Comment: 20 pages, 8 figures, new data and simulation

Controlling spin relaxation with a cavity

Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized that the spontaneous emission rate can be strongly enhanced by placing the quantum system in a resonant cavity -an effect which has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave or optical cavities, underpinning single-photon sources. Here we report the first application of these ideas to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity of high quality factor and small mode volume, we reach for the first time the regime where spontaneous emission constitutes the dominant spin relaxation mechanism. The relaxation rate is increased by three orders of magnitude when the spins are tuned to the cavity resonance, showing that energy relaxation can be engineered and controlled on-demand. Our results provide a novel and general way to initialise spin systems into their ground state, with applications in magnetic resonance and quantum information processing. They also demonstrate that, contrary to popular belief, the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point where quantum fluctuations have a dramatic effect on the spin dynamics; as such our work represents an important step towards the coherent magnetic coupling of individual spins to microwave photons.Comment: 8 pages, 6 figures, 1 tabl

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

NeuN/Rbfox3 Nuclear and Cytoplasmic Isoforms Differentially Regulate Alternative Splicing and Nonsense-Mediated Decay of Rbfox2

Anti-NeuN (Neuronal Nuclei) is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45–50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors), confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45–50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism

NeuN/Rbfox3 Nuclear and Cytoplasmic Isoforms Differentially Regulate Alternative Splicing and Nonsense-Mediated Decay of Rbfox2

Anti-NeuN (Neuronal Nuclei) is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45–50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors), confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45–50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism

The CUGBP2 Splicing Factor Regulates an Ensemble of Branchpoints from Perimeter Binding Sites with Implications for Autoregulation

Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition of information-poor sequence motifs. The CUGBP2 splicing regulator plays a key role in the brain region-specific silencing of the NI exon of the NMDA R1 receptor. However, the sequence motifs utilized by this factor for specific target exon selection and its role in splicing silencing are not understood. Here, we use chemical modification footprinting to map the contact sites of CUGBP2 to GU-rich motifs closely positioned at the boundaries of the branch sites of the NI exon, and we demonstrate a mechanistic role for this specific arrangement of motifs for the regulation of branchpoint formation. General support for a branch site-perimeter–binding model is indicated by the identification of a group of novel target exons with a similar configuration of motifs that are silenced by CUGBP2. These results reveal an autoregulatory role for CUGBP2 as indicated by its direct interaction with functionally significant RNA motifs surrounding the branch sites upstream of exon 6 of the CUGBP2 transcript itself. The perimeter-binding model explains how CUGBP2 can effectively embrace the branch site region to achieve the specificity needed for the selection of exon targets and the fine-tuning of alternative splicing patterns

Decoherence in Crystals of Quantum Molecular Magnets

Decoherence in Nature has become one of the most pressing problems in physics. Many applications, including quantum information processing, depend on understanding it; and fundamental theories going beyond quantum mechanics have been suggested [1-3], where the breakdown of quantum theory appears as an 'intrinsic decoherence', mimicking environmental decoherence [4]. Such theories cannot be tested until we have a handle on ordinary environmental decoherence processes. Here we show that the theory for insulating electronic spin systems can make accurate predictions for environmental decoherence in molecular-based quantum magnets [5]. Experimental understanding of decoherence in molecular magnets has been limited by short decoherence times, which make coherent spin manipulation extremely difficult [6-9]. Here we reduce the decoherence by applying a strong magnetic field. The theory predicts the contributions to the decoherence from phonons, nuclear spins, and intermolecular dipolar interactions, for a single crystal of the Fe8 molecular magnet. In experiments we find that the decoherence time varies strongly as a function of temperature and magnetic field. The theoretical predictions are fully verified experimentally - there are no other visible decoherence sources. Our investigation suggests that the decoherence time is ultimately limited by nuclear spins, and can be extended up to about 500 microseconds, by optimizing the temperature, magnetic field, and nuclear isotopic concentrations.Comment: Submitted version including 11 pages, 3 figures and online supporting materials. Appeared on Nature Advance Online Publication (AOP) on July 20th, 2011. (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10314.html

A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis

BACKGROUND: Alternative pre-mRNA splicing (AS) plays a central role in generating complex proteomes and influences development and disease. However, the regulation and etiology of AS in human tumorigenesis is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: A Basic Local Alignment Search Tool database was constructed for the expressed sequence tags (ESTs) from all available databases of human cancer and normal tissues. An insertion or deletion in the alignment of EST/EST was used to identify alternatively spliced transcripts. Alignment of the ESTs with the genomic sequence was further used to confirm AS. Alternatively spliced transcripts in each tissue were then subtractively cross-screened to obtain tissue-specific variants. We systematically identified and characterized cancer/tissue-specific and alternatively spliced variants in the human genome based on a global view. We identified 15,093 cancer-specific variants of 9,989 genes from 27 types of human cancers and 14,376 normal tissue-specific variants of 7,240 genes from 35 normal tissues, which cover the main types of human tumors and normal tissues. Approximately 70% of these transcripts are novel. These data were integrated into a database HCSAS (http://202.114.72.39/database/human.html, pass:68756253). Moreover, we observed that the cancer-specific AS of both oncogenes and tumor suppressor genes are associated with specific cancer types. Cancer shows a preference in the selection of alternative splice-sites and utilization of alternative splicing types. CONCLUSIONS/SIGNIFICANCE: These features of human cancer, together with the discovery of huge numbers of novel splice forms for cancer-associated genes, suggest an important and global role of cancer-specific AS during human tumorigenesis. We advise the use of cancer-specific alternative splicing as a potential source of new diagnostic, prognostic, predictive, and therapeutic tools for human cancer. The global view of cancer-specific AS is not only useful for exploring the complexity of the cancer transcriptome but also widens the eyeshot of clinical research

Seek Help from Teachers or Fight Back? Student Perceptions of Teachers’ Actions during Conflicts and Responses to Peer Victimization

Previous research has shown that teachers’ actions when addressing conflict on school grounds can shape adolescent perceptions regarding how well the school manages victimization. Our objective in this study was to determine how these perceptions influenced the likelihood that adolescent students would react to victimization scenarios by either seeking help from school authority or physically fighting back. Vignettes describing two events of victimization were administered to 148 ethnic minority adolescents (Latino, African American, and Asian backgrounds; 49% female) attending an urban high school with high rates of conflict. Positive perceptions of teachers’ actions during conflicts—assessed via a questionnaire tapping how teachers manage student conflicts both generally and in a specific instance of strife—predicted a greater willingness to seek help from school authority, which in turn negatively predicted self-reported aggressive responses to the victimization scenarios. Path analysis established the viability of this indirect effect model, even when we controlled for sex, beliefs about the acceptability of aggression, and previous levels of reactive aggression. Adolescents’ perceptions of teachers’ actions during conflicts are discussed in relation to social information processing models, improving student–teacher relations, and decreasing aggression at schools