The brattleboro rat displays a natural deficit in social discrimination that is restored by clozapine and a neurotensin analog.

Cognitive deficits in schizophrenia are a major source of dysfunction for which more effective treatments are needed. The vasopressin-deficient Brattleboro (BRAT) rat has been shown to have several natural schizophrenia-like deficits, including impairments in prepulse inhibition and memory. We investigated BRAT rats and their parental strain, Long-Evans (LE) rats, in a social discrimination paradigm, which is an ethologically relevant animal test of cognitive deficits of schizophrenia based upon the natural preference of animals to investigate conspecifics. We also investigated the effects of the atypical antipsychotic, clozapine, and the putative antipsychotic, PD149163, a brain-penetrating neurotensin-1 agonist, on social discrimination in these rats. Adult rats were administered saline or one of the three doses of clozapine (0.1, 1.0, or 10 mg/kg) or PD149163 (0.1, 0.3, or 1.0 mg/kg), subcutaneously. Following drug administration, adult rats were exposed to a juvenile rat for a 4-min learning period. Animals were then housed individually for 30 min and then simultaneously exposed to the juvenile presented previously and a new juvenile for 4 min. Saline-treated LE rats, but not BRAT rats, exhibited intact social discrimination as evidenced by greater time spent exploring the new juvenile. The highest dose of clozapine and the two highest doses of PD149163 restored social discrimination in BRAT rats. These results provide further support for the utility of the BRAT rat as a genetic animal model relevant to schizophrenia and drug discovery. The potential of neurotensin agonists as putative treatments for cognitive deficits of schizophrenia was also supported

Photoionization in the time and frequency domain

Ultrafast processes in matter, such as the electron emission following light absorption, can now be studied using ultrashort light pulses of attosecond duration ($10^{-18}$s) in the extreme ultraviolet spectral range. The lack of spectral resolution due to the use of short light pulses may raise serious issues in the interpretation of the experimental results and the comparison with detailed theoretical calculations. Here, we determine photoionization time delays in neon atoms over a 40 eV energy range with an interferometric technique combining high temporal and spectral resolution. We spectrally disentangle direct ionization from ionization with shake up, where a second electron is left in an excited state, thus obtaining excellent agreement with theoretical calculations and thereby solving a puzzle raised by seven-year-old measurements. Our experimental approach does not have conceptual limits, allowing us to foresee, with the help of upcoming laser technology, ultra-high resolution time-frequency studies from the visible to the x-ray range.Comment: 5 pages, 4 figure

Competition between folded and extended structures of alanylalanine (Ala-Ala) in a molecular beam

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Cationic double K-hole pre-edge states of CS2 and SF6

Recent advances in X-ray instrumentation have made it possible to measure the spectra of an essentially unexplored class of electronic states associated with double inner-shell vacancies. Using the technique of single electron spectroscopy, spectra of states in CS2 and SF6 with a double hole in the K-shell and one electron exited to a normally unoccupied orbital have been obtained. The spectra are interpreted with the aid of a high-level theoretical model giving excellent agreement with the experiment. The results shed new light on the important distinction between direct and conjugate shake-up in a molecular context. In particular, systematic similarities and differences between pre-edge states near single core holes investigated in X-ray absorption spectra and the corresponding states near double core holes studied here are brought out

Experimental Verification of the Chemical Sensitivity of Two-Site Double Core-Hole States Formed by an X-ray FEL

We have performed X-ray two-photon photoelectron spectroscopy (XTPPS) using the Linac Coherent Light Source (LCLS) X-ray free-electron laser (FEL) in order to study double core-hole (DCH) states of CO2, N2O and N2. The experiment verifies the theory behind the chemical sensitivity of two-site (ts) DCH states by comparing a set of small molecules with respect to the energy shift of the tsDCH state and by extracting the relevant parameters from this shift.Comment: 11 pages, 2 figure

Promise and Pitfalls of Animal Models of Schizophrenia

Animal models are indispensible tools for advancing understanding of the cause of any given disease and developing new treatments. Developing animal models for schizophrenia presents formidable challenges owing to the distinctively human nature of the symptoms that define it and the thus-far-obscured underlying biological mechanisms. Nevertheless, progress has been and continues to be made in this important field of endeavor. This article discusses the challenges facing investigators who seek to develop and use animal models for translational research in schizophrenia and the responses that have emerged to those challenges, as well as the likely pathways that will lead to future progress