Calcium-independent inhibitory G-protein signaling induces persistent presynaptic muting of hippocampal synapses

Adaptive forms of synaptic plasticity that reduce excitatory synaptic transmission in response to prolonged increases in neuronal activity may prevent runaway positive feedback in neuronal circuits. In hippocampal neurons, for example, glutamatergic presynaptic terminals are selectively silenced, creating mute synapses, after periods of increased neuronal activity or sustained depolarization. Previous work suggests that cAMP-dependent and proteasome-dependent mechanisms participate in silencing induction by depolarization, but upstream activators are unknown. We, therefore, tested the role of calcium and G-protein signaling in silencing induction in cultured hippocampal neurons. We found that silencing induction by depolarization was not dependent on rises in intracellular calcium, from either extracellular or intracellular sources. Silencing was, however, pertussis toxin sensitive, which suggests that inhibitory G-proteins are recruited. Surprisingly, blocking four common inhibitory G-protein-coupled receptors (GPCRs) (adenosine A(1) receptors, GABA(B) receptors, metabotropic glutamate receptors, and CB(1) cannabinoid receptors) and one ionotropic receptor with metabotropic properties (kainate receptors) failed to prevent depolarization-induced silencing. Activating a subset of these GPCRs (A(1) and GABA(B)) with agonist application induced silencing, however, which supports the hypothesis that G-protein activation is a critical step in silencing. Overall, our results suggest that depolarization activates silencing through an atypical GPCR or through receptor-independent G-protein activation. GPCR agonist-induced silencing exhibited dependence on the ubiquitin-proteasome system, as was shown previously for depolarization-induced silencing, implicating the degradation of vital synaptic proteins in silencing by GPCR activation. These data suggest that presynaptic muting in hippocampal neurons uses a G-protein-dependent but calcium-independent mechanism to depress presynaptic vesicle release

Spectral Line De-confusion in an Intensity Mapping Survey

Spectral line intensity mapping has been proposed as a promising tool to efficiently probe the cosmic reionization and the large-scale structure. Without detecting individual sources, line intensity mapping makes use of all available photons and measures the integrated light in the source confusion limit, to efficiently map the three-dimensional matter distribution on large scales as traced by a given emission line. One particular challenge is the separation of desired signals from astrophysical continuum foregrounds and line interlopers. Here we present a technique to extract large-scale structure information traced by emission lines from different redshifts, embedded in a three-dimensional intensity mapping data cube. The line redshifts are distinguished by the anisotropic shape of the power spectra when projected onto a common coordinate frame. We consider the case where high-redshift [CII] lines are confused with multiple low-redshift CO rotational lines. We present a semi-analytic model for [CII] and CO line estimates based on the cosmic infrared background measurements, and show that with a modest instrumental noise level and survey geometry, the large-scale [CII] and CO power spectrum amplitudes can be successfully extracted from a confusion-limited data set, without external information. We discuss the implications and limits of this technique for possible line intensity mapping experiments.Comment: 13 pages, 14 figures, accepted by Ap

Understanding factors relevant to poor sleep and coping methods in people with schizophrenia

Background Sleep disruption is pervasive in people with schizophrenia, but few studies have explored their sleep experiences. This study aims to identify factors relevant to sleep problems and explore coping methods used by community-dwelling people with schizophrenia. Methods Eighteen participants with schizophrenia were recruited from three mental health centers in Taiwan. They completed a semi-structured interview and the Pittsburgh Sleep Quality Index (PSQI) assessment. The Person-Environment-Occupation model offered a framework to assess factors related to sleep. Thematic analysis was used for the qualitative data analysis. Results Factors related to sleep were classified under person, environment, and occupation domains. The person domain included three subthemes: psychiatric symptoms, unpleasant emotions, and frustration about sleep. The environment domain included three subthemes: sensory intrusions from the environment, quality of bedding, and roommates. The occupation domain included sleep interruption and sleep preparation. There were notable discrepancies in sleep quality between the participants’ narratives and their PSQI global scores. Regarding coping methods for poor sleep, sleep medication was the primary strategy while some participants also used other strategies, such as modifying the environment, adjusting routines, or engaging in activities that improve sleep quality. Conclusions Psychiatric symptoms and nightmares were identified as unique sleep disruptions in people with schizophrenia, and poor economic status was also found to impact their sleep. The sleep quality of people with schizophrenia tends to be poor, as identified by the PSQI, even though they may have positive perceptions of their sleep quality. Our participants appeared to prefer to take hypnotics to address their sleep problems, which may be due to limited knowledge about alternatives. Mental health professionals are encouraged to receive training in the application of non-pharmacological approaches to support their clients’ issues related to sleep

Z0Z_0 Boson Decays to Bc(∗)B^{(*)}_c Meson and Its Uncertainties

The programming new $e^{+}e^-$ collider with high luminosity shall provide another useful platform to study the properties of the doubly heavy $B_c$ meson in addition to the hadronic colliders as LHC and TEVATRON. Under the `New Trace Amplitude Approach', we calculate the production of the spin-singlet $B_c$ and the spin-triplet $B^*_c$ mesons through the $Z^0$ boson decays, where uncertainties for the production are also discussed. Our results show $\Gamma_{(^1S_0)}= 81.4^{+102.1}_{-40.5}$ KeV and $\Gamma_{(^3S_1)}=116.4^{+163.9}_{-62.8}$ KeV, where the errors are caused by varying $m_b$ and $m_c$ within their reasonable regions.Comment: 11 pages, 5 figures, 2 tables. To be published in Eur.Phys.J.

Cryptococcus neoformans Overcomes Stress of Azole Drugs by Formation of Disomy in Specific Multiple Chromosomes

Cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in AIDS patients. Fluconazole (FLC), a triazole, is widely used for the maintenance therapy of cryptococcosis. Heteroresistance to FLC, an adaptive mode of azole resistance, was associated with FLC therapy failure cases but the mechanism underlying the resistance was unknown. We used comparative genome hybridization and quantitative real-time PCR in order to show that C. neoformans adapts to high concentrations of FLC by duplication of multiple chromosomes. Formation of disomic chromosomes in response to FLC stress was observed in both serotype A and D strains. Strains that adapted to FLC concentrations higher than their minimal inhibitory concentration (MIC) contained disomies of chromosome 1 and stepwise exposure to even higher drug concentrations induced additional duplications of several other specific chromosomes. The number of disomic chromosomes in each resistant strain directly correlated with the concentration of FLC tolerated by each strain. Upon removal of the drug pressure, strains that had adapted to high concentrations of FLC returned to their original level of susceptibility by initially losing the extra copy of chromosome 1 followed by loss of the extra copies of the remaining disomic chromosomes. The duplication of chromosome 1 was closely associated with two of its resident genes: ERG11, the target of FLC and AFR1, the major transporter of azoles in C. neoformans. This adaptive mechanism in C. neoformans may play an important role in FLC therapy failure of cryptococcosis leading to relapse during azole maintenance therapy