Zebrafish studies identify serotonin receptors mediating antiepileptic activity in Dravet syndrome.

Dravet syndrome is a life-threatening early-onset epilepsy not well controlled by antiepileptic drugs. Drugs that modulate serotonin (5-HT) signalling, including clemizole, locaserin, trazodone and fenfluramine, have recently emerged as potential treatment options for Dravet syndrome. To investigate the serotonin receptors that could moderate this antiepileptic activity, we designed and synthesized 28 novel analogues of clemizole, obtained receptor binding affinity profiles, and performed in vivo screening in a scn1lab mutant zebrafish (Danio rerio) model which recapitulates critical clinical features of Dravet syndrome. We discovered three clemizole analogues with 5-HT receptor binding that exert powerful antiepileptic activity. Based on structure-activity relationships and medicinal chemistry-based analysis, we then screened an additional set of known 5-HT receptor specific drug candidates. Integrating our in vitro and in vivo data implicates 5-HT2B receptors as a critical mediator in the mechanism of seizure suppression observed in Dravet syndrome patients treated with 5-HT modulating drugs

A Propensity-Matched Analysis of Outcomes for Patients With M2 Branch Occlusions at Endovascular Stroke Centers

Introduction: Endovascular therapy (EVT) for Emergent Large Vessel Occlusion (ELVO) is recommended for patients with acute proximal MCA (M1 segment) occlusions (Class I, level A evidence), but the benefits of EVT are uncertain in patients with M2 and more distal occlusions. The purpose of this study was to compare the efficacy and outcomes of EVT-treated M2 ELVOs with EVT-treated M1 ELVOs, and to examine the outcomes of EVT-treated M2 ELVO patients with those whose M2 ELVOs were not treated. Methods: Data were obtained from a multi-hospital system of patients from January 2014 and May 2018. Two propensity score (PS)-based nearest-neighbor matching analyses were used to match similar patients who had 1) EVT-treated M1 vs EVT-treated M2 ELVOs and 2) EVT-treated vs non-EVT-treated M2 ELVOs. Outcomes included length of stay (LOS), rate of successful reperfusion, discharge disposition, symptomatic intracranial hemorrhage (sICH), and discharge mRS. Chi-squared, Fisher’s exact, and Mann-Whitney U tests were used to compare matched patients. Results: Overall, 160 patients with EVT-treated M2 ELVOs, 350 with EVT-treated M1 ELVOs, and 113 with non-EVT-treated M2 ELVOs were included. Propensity score analyses resulted in 118 matched patients with EVT-treated M2 and EVT-treated M1 occlusions and 70 matched patients with EVT-treated and non-EVT-treated M2 ELVOs. M2 ELVOs made up 20% of all LVO patients. Treated M1 and M2 ELVOs were similar with respect to baseline NIHSS and outcomes. When attempted,intra-arterial reperfusion of M2 ELVOs was achieved at comparable rates to M1 ELVOs with equal rates of sICH (1.7%). Higher NIHSS was associated with EVT of M2 ELVOs (15.00[8.50,21.00] vs 7.00[4.00,17.75]; p\u3c0.001). Rates of mortality trended more favorably in treated M2 ELVOs (12.9% vs 20), which was not statistically significant (p=0.362). Conclusions: EVT for M2 ELVOs is as safe and effective as EVT for M1 vessel ELVOs. Rates of successful reperfusion, discharge mRS, LOS, sICH, discharge disposition and mortality are similar among EVT treated M2 and EVT treated M1 ELVOs. Though not statistically significant, EVT for patients with M2 ELVOs resulted in favorable trends toward higher survival rates of potential clinical significance

A selective role for neuronal activity regulated pentraxin in the processing of sensory-specific incentive value

Neuronal activity regulated pentraxin (Narp) is a secreted neuronal product which clusters AMPA receptors and regulates excitatory synaptogenesis. Although Narp is selectively enriched in brain, its role in behavior is not known. As Narp is expressed prominently in limbic regions, we examined whether Narp deletion affects performance on tasks used to assess motivational consequences of food-rewarded learning. Narp knock-out (KO) mice were unimpaired in learning simple pavlovian discriminations, instrumental lever pressing, and in acquisition of at least two aspects of pavlovian incentive learning, conditioned reinforcement and pavlovian-instrumental transfer. In contrast, Narp deletion resulted in a substantial deficit in the ability to use specific outcome expectancies to modulate instrumental performance in a devaluation task. In this task, mice were trained to respond on two levers for two different rewards. After training, mice were prefed with one of the two rewards, devaluing it. Responding on both levers was then assessed in extinction. Whereas control mice showed a significant preference in responding on the lever associated with the nondevalued reward, Narp KO mice responded equally on both levers, failing to suppress responding on the lever associated with the devalued reward. Both groups consumed more of the nondevalued reward in a subsequent choice test, indicating Narp KO mice could distinguish between the rewards themselves. These data suggest Narp has a selective role in processing sensory-specific information necessary for appropriate devaluation performance, but not in general motivational effects of reward-predictive cues on performance

Light absorption by inhomogeneous semiconductor film

Processes of light absorption by thin semiconductor film in the framework of local-field method are studied. The film is inhomogeneously implanted with O⁺ ions. A distribution of implanted layer is characterized by different profiles. The effective susceptibility (response to the external field) and dissipative function of inhomogeneous in thickness semiconductor film were calculated. The absorption spectra are numerically calculated as a function of the frequency and angle of incidence. It was obtain that light absorption spectra are strongly dependent on profile distributions of implanted impurities along the film thickness

Research of generalized immittance converter on the field-effect transistor with polarity reversal of voltage on the gate

Досліджено узагальнений перетворювач іммітансу на польовому транзисторі при позитивній та негативній полярності напруги на затворі від індуктивного іммітансу навантаження.Generalized immittance converter (GIC) on field-effect transistor with a p-n-junction (JFET) and with positive and negative polarity voltage on the gate of inductive immittance load was studied. JFET is included in the scheme with common source. Physical equivalent circuit JFET at different voltage polarity on the gate was interpritated. Dependences of the input resistance of the load resistance at various gate voltage polarity was investigated. The diagrams of Volpert-Smit were built. The conditions under which JFET can be used as a converter and inverter of immittance without changing the connection circuit were specified. With the negative polarity of voltage on the gate JFET possesses properties of immittance inverter, with a positive polarity of voltage on the gate JFET possesses properties of immittance converter. In general, the structures of JFET with p-n junction is similar to the structures of UJT and IST, which allows in certain modes to describe it by the similar physical small-signal equivalent circuits. The main difference is in the length and resistance of the channel (base), which significantly affects the nature of the physical processes in it. Using the JFET in direct displacement of p-n junction it is necessary to describe the T-shaped equivalent circuit which is used for the bipolar transistor, the realized GIC possessing properties of immittance converter. Application of JFET as a converter or inverter of immittance without changing of the connection circuit is limited by the quantity of the immittance transformation and relative frequency Ω

Anisotropic Instabilities in Trapped Spinor Bose-Einstein Condensates

We theoretically investigate the effect of an anisotropic trap on the instability of the polar $(m_F=0)$ phase of a spin-1 Bose-Einstein condensate. By considering rigorously the spatial quantization, we show that the growth of the nascent ferromagnetic phase at short times becomes anisotropic with stronger oscillations in the magnetization correlation function along the unconfined direction.Comment: 8 pages, 6 figure

Discovery of SiCSi in IRC+10216: A missing link between gas and dust carriers of SiC bonds

We report the discovery in space of a disilicon species, SiCSi, from observations between 80 and 350 GHz with the IRAM 30m radio telescope. Owing to the close coordination between laboratory experiments and astrophysics, 112 lines have now been detected in the carbon-rich star CWLeo. The derived frequencies yield improved rotational and centrifugal distortion constants up to sixth order. From the line profiles and interferometric maps with the Submillimeter Array, the bulk of the SiCSi emis- sion arises from a region of 6 arcseconds in radius. The derived abundance is comparable to that of SiC2. As expected from chemical equilibrium calculations, SiCSi and SiC2 are the most abundant species harboring a SiC bond in the dust formation zone and certainly both play a key role in the formation of SiC dust grains.Comment: To be published in the Astrophysical Journal Letters; Accepted May 6 201