The developmental process of flood shoals based on observations in Toufutsu lake, Japan

Recently, the flood tidal sand bars have been developed at the entrance channel of Toufutsu Lake located along Okhotsk Sea in Hokkaido, and they affect flood control, inland water fisheries in lake, and so forth. In this study, we aimed to reveal the developmental process of sand bars by observations, which are velocity observation, water level observation, bed material investigation and video monitoring. Followings were major accomplishments of this study. (1) The maximum magnitude of reverse velocity at St.400 in the entrance channel during the periods of flood-tide was faster than that of normal velocity during the periods of ebb-tide. (2) The relationship between velocity at SP400 and friction velocity at SP400 during the periods of flood-tide is different from that during the periods of ebb-tide. (3) The\ud flood tidal sand bars at the entrance channel of Toufutsu Lake were developed by not only sea waves, but also adverse tidal current in the spring-tide

New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration

After brain injury, neural stem cell–derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast mi-gration is restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts use Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neu-roblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. These neuroblasts matured into striatal neurons and efficiently regenerated neuronal circuits, resulting in functional recovery in the poststroke mice. These results suggest that the positioning of new neurons will be critical for func-tional neuronal regeneration in stem/progenitor cell–based therapies for brain injury

Neuroimaging at 7 Tesla: a pictorial narrative review

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Axonal Control of the Adult Neural Stem Cell Niche

SUMMARYThe ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C

Recent Results From a Si/CdTe Semiconductor Compton Telescope

We are developing a Compton telescope based on high resolution Si and CdTe detectors for astrophysical observations in sub-MeV/MeV gamma-ray region. Recently, we constructed a prototype Compton telescope which consists of six layers of double-sided Si strip detectors and CdTe pixel detectors to demonstrate the basic performance of this new technology. By irradiating the detector with gamma-rays from radio isotope sources, we have succeeded in Compton reconstruction of images and spectra. The obtained angular resolution is 3.9{sup o} (FWHM) at 511 keV, and the energy resolution is 14 keV (FWHM) at the same energy. In addition to the conventional Compton reconstruction, i.e., drawing cones in the sky, we also demonstrated a full reconstruction by tracking Compton recoil electrons using the signals detected in successive Si layers. By irradiating {sup 137}Cs source, we successfully obtained an image and a spectrum of 662 keV line emission with this method. As a next step, development of larger double-sided Si strip detectors with a size of 4 cm x 4 cm is underway to improve the effective area of the Compton telescope. We are also developing a new low-noise analog ASIC to handle the increasing number of channels. Initial results from these two new technologies are presented in this paper as well

Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model

Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D2 autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD

Dizajniranje i vrednovanje bioadhezijskog filma za transdermalnu isporuku propranolol hidroklorida

The objective of the study was to develop a suitable transdermal delivery system for propranolol hydrochloride (PPL) via employing chitosan as a film former. Drug concentration uniformity, thickness, moisture uptake capacity and skin bioadhesion of the films were characterized. The effects of chitosan and PPL concentration and different penetration enhancers on the release and permeation profiles from the films were investigated. Skin irritation of the candidate film was evaluated. Chitosan film (PPL 2 mg cm2, chitosan 2 % m/m, cineol 10 %, m/m) was found non-irritant and achieved 88.2 % release after 8 hours in phosphate buffer. Significant high (p < 0.001) permeation of PPL through rat skin was obtained using this film compared to the film without enhancer (about 8 times enhancement factor), making it a promising transdermal delivery system for PPL.Cilj rada bio je razvoj pogodnog transdermalnog sustava na bazi kitozana za isporuku propranolol hidroklorida (PPL). Svim pripravcima ispitana je jednoličnost udjela lijeka, debljina, sposobnost vlaženja i bioadhezivnost na kožu. Ispitivan je i utjecaj kitozana, koncentracije PPL-a i sredstva za povećanje permeacije na oslobađanje i permeacijski profil, te potencijalni iritacijski učinak na kožu. Iz kitozanskog filma (PPL 2 mg cm2, 2 %, m/m, kitozana i 10 %, m/m, cineola), koji nije djelovao iritabilno, postignuto je 88,2 % oslobađanja nakon 8 sati u fosfatnom puferu. S ovim pripravkom postignuta je i vrlo značajna (p < 0,001) permeacija PPL kroz kožu štakora, oko osam puta veća u usporedbi s filmom bez sredstva za povećanje permeacije. Pripravak bi se mogao upotrijebiti za transdermalnu isporuku PPL