Reduced Rate of Neural Differentiation in the Dentate Gyrus of Adult Dysbindin Null (Sandy) Mouse

Genetic variations in the gene encoding dysbindin has consistently been associated with schizophrenia and bipolar disorder, although little is known about the neural functions carried out by dysbindin. To gain some insight into this area, we took advantage of the readily available dysbindin-null mouse sandy (sdy−/−) and studied hippocampal neurogenesis using thymidine analogue bromodeoxuridine (BrdU). No significant differences were found in the proliferation (4 hours) or survival (1, 4 and 8 weeks after the last BrdU injection) of progenitors in the subgranular regions of the dentate gyrus between sdy−/− and sdy+/+ (control) mice. However, 4 weeks after the last BrdU injection, a significant reduction was observed in the ratio of neuronal differentiation in sdy−/− when compared to that of sdy+/+ (sdy+/+  = 87.0±5.3% vs. sdy−/−  = 71.3±8.3%, p = 0.01). These findings suggest that dysbindin plays a role during differentiation process in the adult hippocampal neurogenesis and that its deficit may negatively affect neurogenesis-related functions such as cognition and mood

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Numerical and experimental study on splash formation with consideration of the surface condition of solid wall

ABSTRACT The purpose of the present paper is to propose a method to simulate the splash formation taking account of the surface condition of the solid plunging into water. Usually, the boundary condition between the solid and the fluid is supposed to be "no-slip" in the simulation of the fluid structure interaction (FSI). We discuss in this paper, however, that the above no-slip condition in the simulation is not always valid. First, we have experimentally studied the patterns of splashes caused by different spheres diving into water, showing that the splash by the hydro-gel sphere is the crown-type one, whereas the acrylic sphere creates the column-type one despite the same experimental condition Regarding the numerical models, we propose two diffrent methods of MPS method. First, as an engineering model to express the slimy surface, the slip ratio, which is the reduction ratio of the shear stress near a solid wall obtained through the experiment, is introduced in the shear term of the Navier-Stokes equation. Second, the effect of the electric attractive/repulsive type force observed in the acrylic resin is introduced into the Navier-Stokes equation as the external force. The splash patterns calculated with the above proposed models and the 3D large scale parallel computing are in good agreement with the experimental results. REFERENCES [1] M. Yokoyama, Y. Kubota, K. Kikuchi, G. Yagawa, and O. Mochizuki, "Some remarks on surface conditions of solid body plunging into water with particle method" Advanced Modellin

Fault size and depth extent of the Ecuador earthquake (M<inf>w</inf> 7.8) of 16 April 2016 from teleseismic and tsunami data

The April 2016 Ecuador Mw 7.8 earthquake was the first megathrust tsunamigenic earthquake along the Ecuador-Colombia subduction zone since 1979 (Mw 8.2 with 200 deaths from tsunami). While there was no tsunami damage from the 2016 earthquake, small tsunamis were recorded at DART and tide gauges. Here, we designed various fault models with and without shallow-slip area, and compared the computed teleseismic and tsunami waveforms with the observations. While teleseismic inversions were indifferent about inclusion or exclusion of the shallow slip, tsunami waveforms strongly favored the slip model without shallow slip. Our final slip model has a depth range of 15–44 km and its western shallowest limit is located at the distance of ~60 km from the trench. Maximum and average slips were 2.5 and 0.7 m, respectively. The large-slip area was 80 km (along strike) × 60 km (along dip) in the depth range of 15–35 km

Effect of impact ionization on the saturation of 1s→2p+ shallow donor transition in n-GaAs

The magneto-photoconductivity due to 1s-2p+ optical transitions of shallow donors in n-GaAs has been investigated as a function of intensity for several bias voltages at low temperatures between 2K and 4.2 K. At low intensities a superlinear increase of the photoconductive signal with rising intensity has been observed which gets more pronounced at higher bias voltages and lower temperatures. The power broadening of the linewidth was found to be distinctly different from the behaviour expected for a two-level system. By a detailed analysis in terms of a nonlinear generation-recombination model it is shown that these effects may be attributed to impact ionization of the optically excited 2p+ states

Source model of the 16 September 2015 Illapel, Chile, M<inf>w</inf> 8.4 earthquake based on teleseismic and tsunami data

We proposed a source model for the 16 September 2015 Illapel (Chile) tsunamigenic earthquake using teleseismic and tsunami data. The 2015 epicenter was at the northernmost of the aftershocks zone of the 2010 Mw 8.8 Maule earthquake. Teleseismic body wave inversions and tsunami simulations showed optimum rupture velocities of 1.5–2.0 km/s. The agreement between observed and synthetic waveforms was quantified using normalized root-mean-square (NRMS) misfit. The variations of NRMS misfits were larger for tsunami data compared to the teleseismic data, because tsunami waveforms are more sensitive to the spatial distribution of slip. The large-slip area was 80 km (along strike) × 100 km (along dip) with an average slip of 5.0 m and depth of 12–33 km, located ~70 km to the northwest of the epicenter. We obtained a seismic moment of 4.42 × 1021 Nm equivalent to Mw 8.4. Results may indicate a northward stress transfer from the 2010 Maule earthquake.Teleseismic data were provided by the Incorporated Research Institutions for Seismology (http://www.iris.edu/wilber3/find_event). Tide gauge data can be found at the Intergovernmental Oceanographic Commission website (http://www.ioc-sealevelmonitoring.org/). DART records were provided by NOAA (http://nctr.pmel.noaa.gov/Dart/). Earthquake catalogs by the USGS National Earthquake Information Center (http://earthquake.usgs.gov/earthquakes/search/) and Global Instrumental Earthquake Catalogue (1900-2009) of International Seismological Centre Global Earthquake Model (http://www.globalquakemodel.org/what/seismic-hazard/instrumental-catalogue/) were used in this study. We used the GMT software for drawing the figures [Wessel and Smith, 1998]. This article benefited from constructive review comments by Costas E. Synolakis (University of Southern California, USA) and Yuichiro Tanioka (Hokkaido University, Japan) for which we are grateful. We acknowledge financial supports from the Japan Society for the Promotion of Science

Deep-Water Characteristics of the Trans-Pacific Tsunami from the 1 April 2014 M w 8.2 Iquique, Chile Earthquake

© 2014, Springer Basel.We studied the tsunami generated by the 1 April 2014 Mw 8.2 Iquique (Chile) earthquake using 20 Deep-ocean Assessment and Reporting of Tsunamis (DART) records and applying Fourier and wavelet analyses as well as performing numerical simulations. Deep-water tsunami wave heights were in the range of 0.8–35.0 cm. For the stations located more than 2,200 km from the source, the average wave height was 1.7 ± 1.1 cm. The observed tsunami arrivals were delayed by 1–17 min relative to the simulated ones based on the linear long wave equations, and the delays were proportional to the tsunami travel distances. A small initial depression was observed at DART stations located at distances >10,000 km from the source whereas, traditionally, an initial elevation is expected at stations located seaward of subduction zones. Fourier analyses showed tsunami governing periods of 21.1 ± 1.7 and 14.7 ± 0.7 min, corresponding to a fault length of 60–70 km and a fault width of 40–45 km. While the two 21-min and 15-min signals appeared in most DART stations during ~0.5 h following the conventional arrival times, the 15-min signal was delayed at some far-field stations. Distribution of maximum DART wave heights across the Pacific Ocean did not show a meaningful relation between maximum DART wave heights and directivity or distance from the source.The sea level data used in this study were provided through the USA National Oceanographic and Atmospheric Administration (NOAA). We thank Hiroshi Tsuruoka and Takeo Ishibe at the Earthquake Research Institute (ERI) for assisting in preparation of some figures. Several figures were drafted using the GMT software (Wessel and Smith 1991). We are sincerely grateful to Prof. Alexander Rabinovich, the editor, and two anonymous reviewers for comments that improved this article. This study is supported by the Japan Society for the Promotion of Science (JSPS)

Fault slip distribution of the 2014 Iquique, Chile, earthquake estimated from ocean-wide tsunami waveforms and GPS data

We applied a new method to compute tsunami Green’s functions for slip inversion of the 1 April 2014 Iquique earthquake using both near-field and far-field tsunami waveforms. Inclusion of the effects of the elastic loading of seafloor, compressibility of seawater, and the geopotential variation in the computed Green’s functions reproduced the tsunami travel-time delay relative to long-wave simulation, and allowed us to use far-field records in tsunami waveform inversion. Multiple time window inversion was applied to tsunami waveforms iteratively until the result resembles the stable moment-rate function from teleseismic inversion. We also used GPS data for a joint inversion of tsunami waveforms and co-seismic crustal deformation. The major slip region with a size of 100 km × 40 km is located down-dip the epicenter at depth ~28 km, regardless of assumed rupture velocities. The total seismic moment estimated from the slip distribution is 1.24 × 1021 Nm (Mw 8.0)