Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers

Mossy fibers, the dentate granule cell axons, are generated throughout an animal's lifetime. Mossy fiber paths and synapses are primarily restricted to the stratum lucidum within the CA3 region. Brain-derived neurotrophic factor (BDNF), a neurotrophin family protein that activates Trk neurotrophin receptors, is highly expressed in the stratum lucidum in an activity-dependent manner. The addition of a Trk neurotrophin receptor inhibitor, K252a, to cultured hippocampal slices induced aberrant extension of mossy fibers into ectopic regions. BDNF overexpression in granule cells ameliorated the mossy fiber pathway abnormalities caused by a submaximal dose of K252a. A similar rescue was observed when BDNF was expressed in CA3 pyramidal cells, most notably in mossy fibers distal to the expression site. These findings are the first to clarify the role of BDNF in mossy fiber pathfinding, not as an attractant cue but as a regulator, possibly acting in a paracrine manner. This effect of BDNF may be as a signal for new fibers to fasciculate and extend further to form synapses with neurons that are far from active BDNF-expressing synapses. This mechanism would ensure the emergence of new independent dentate gyrus-CA3 circuits by the axons of new-born granule cells

Experimental Verification of Finite Element Analysis for a Thermoplastic Orthodontic Aligner

In recent years, good outcomes have been reported using transparent and removable orthodontic appliances known as aligners. However, unpredicted tooth movement that contradicted 3-dimensional image simulations was observed in some cases. These anomalies could relate to biomechanical factors ; in particular, the characteristics of mechanical loading applied to the periodontal ligament and the tooth crown by aligners remain unclear. This study examines the biomechanical characteristics of aligners by a new method as follows : 1) development of an experimental model using artificial teeth and plastic aligners ; 2) finite element (FE) modeling and analysis using computed tomography (CT) images of the experimental model ; and, 3) comparison among observations of this actual model and standard FE analysis results. Roots of two artificial teeth were covered by silicone material at 1.0 mm intervals for each coronal proximal surface and plastic clear aligners were manufactured based on another model in which the interval was reduced to 0.0 mm to simulate bodily movement. An FE analysis model of this 1.0 mm teeth interval was reconstructed from the CT images. A virtual aligner based on the FE model was also generated with a 0.0 mm interval. Changes in space between the root surface and silicone in both the actual and FE model were compared with the aligner fitted in the initial model. Identical tendencies of movement were observed in both experimental results - the artificial teeth and computational results of FE analysis. Our method using an experimental and computational approach proved useful to examine aligner characteristics ; the use of such a biomechanical approach could further our understanding of aligner treatments

Microcystin degradation in sphingopyxis sp. C-1

The microcystin-degrading gene cluster, mlrA-B-C-D, plaies an important role in the degradation process of hepatotoxic microcystins for several bacterial species. However after microcystin is degraded to linear-microcystin by MlrA, it is still unknown about where and by what it is metabolited. In order to clarify it, we disrupted the mlrB gene and mlrC gene in chromosome of microcystin-degrading bacteria, Sphingopyxis sp. C-1. The cells disrupted mlrB gene and mlrC gene accumulated of microcystin-degradation product, linear-microcystin and tetrapeptide, respectively, whereas the cell free extracts of ?mlrB cells detected Adda and ?mlrC cells accumulated tetrapeptide. Moreover, topology analysis of MlrB using the ß-lactamase gene fusion method insisted MlrB is the peripheral protein binding the inner-membrane. These results insist that MlrB degrades the linear microcystin in the periplasmic space and MlrC degrades tetrapeptide in cytoplasm. Thus, in intact cells, MlrC cannot degrade linear-microcystin as being separated in inner-membrane from linear-microcystin while MlrC is capable of degrading the linear-microcystin in cell-free extract

Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain

<p>Abstract</p> <p>Background</p> <p>X11-family proteins, including X11, X11-like (X11L) and X11-like 2 (X11L2), bind to the cytoplasmic domain of amyloid β-protein precursor (APP) and regulate APP metabolism. Both X11 and X11L are expressed specifically in brain, while X11L2 is expressed ubiquitously. X11L is predominantly expressed in excitatory neurons, in contrast to X11, which is strongly expressed in inhibitory neurons. <it>In vivo </it>gene-knockout studies targeting X11, X11L, or both, and studies of X11 or X11L transgenic mice have reported that X11-family proteins suppress the amyloidogenic processing of endogenous mouse APP and ectopic human APP with one exception: knockout of X11, X11L or X11L2 has been found to suppress amyloidogenic metabolism in transgenic mice overexpressing the human Swedish mutant APP (APPswe) and the mutant human PS1, which lacks exon 9 (PS1dE9). Therefore, the data on X11-family protein function in transgenic human APP metabolism <it>in vivo </it>are inconsistent.</p> <p>Results</p> <p>To confirm the interaction of X11L with human APP ectopically expressed in mouse brain, we examined the amyloidogenic metabolism of human APP in two lines of human APP transgenic mice generated to also lack X11L. In agreement with previous reports from our lab and others, we found that the amyloidogenic metabolism of human APP increased in the absence of X11L.</p> <p>Conclusion</p> <p>X11L appears to aid in the suppression of amyloidogenic processing of human APP in brain <it>in vivo</it>, as has been demonstrated by previous studies using several human APP transgenic lines with various genetic backgrounds. X11L appears to regulate human APP in a manner similar to that seen in endogenous mouse APP metabolism.</p

Change in plasma membrane potential of rat thymocytes by tert-butylhydroquinone, a food additive : Possible risk on lymphocytes

Tertiary butylhydroquinone (TBHQ) is a food additive and has various beneficial actions under in vitro and in vivo experimental conditions. Therefore, it is necessary to collect additional data on the toxicity of TBHQ in order to avoid adverse effects during clinical applications. Changes in plasma membrane potential are associated with changes in physiological functions even in non-excitable cells such as lymphocytes. Thus, compounds that affect membrane potential may modify some lymphocytic functions. The effect of TBHQ on plasma membrane potential was examined in rat thymocytes using flow cytometric techniques. Treatment of rat thymocytes with TBHQ caused hyperpolarization and then depolarization. The TBHQ-induced hyperpolarization was due to the activation of Ca2+-dependent K+ channels. TBHQ elevated intracellular Ca2+ levels. The depolarization by TBHQ was caused by a nonspecific increase in membrane ionic permeability. Both the sustained depolarization and elevation of intracellular Ca2+ level by TBHQ are thought to be adverse for thymocytes because such changes disturb membrane and intracellular signaling. The thymus is most active during neonatal and pre-adolescent periods. If TBHQ exerts adverse actions on thymocytes, it may result in an immunotoxic effect in neonates and adolescents

Cosmic shear statistics in the Suprime-Cam 2.1 sq deg field: Constraints on Omega_m and sigma_8

We present measurements of the cosmic shear correlation in the shapes of galaxies in the Suprime-Cam 2.1 deg^2 R_c-band imaging data. As an estimator of the shear correlation originated from the gravitational lensing, we adopt the aperture mass variance. We detect a non-zero E mode variance on scales between 2 and 40arcmin. We also detect a small but non-zero B mode variance on scales larger than 5arcmin. We compare the measured E mode variance to the model predictions in CDM cosmologies using maximum likelihood analysis. A four-dimensional space is explored, which examines sigma_8, Omega_m, Gamma and zs (a mean redshift of galaxies). We include three possible sources of error: statistical noise, the cosmic variance estimated using numerical experiments, and a residual systematic effect estimated from the B mode variance. We derive joint constraints on two parameters by marginalizing over the two remaining parameters. We obtain an upper limit of Gamma0.9 (68% confidence). For a prior Gamma\in[0.1,0.4] and zs\in[0.6,1.4], we find sigma_8=(0.50_{-0.16}^{+0.35})Omega_m^{-0.37} for flat cosmologies and sigma_8=(0.51_{-0.16}^{+0.29})Omega_m^{-0.34}$ for open cosmologies (95% confidence). If we take the currently popular LCDM model, we obtain a one-dimensional confidence interval on sigma_8 for the 95.4% level, 0.62<\sigma_8<1.32 for zs\in[0.6,1.4]. Information on the redshift distribution of galaxies is key to obtaining a correct cosmological constraint. An independent constraint on Gamma from other observations is useful to tighten the constraint.Comment: 12 pages, 12 figures, accepted for publication in Ap

〈研究ノート〉筑波大学陸域環境研究センター構内における地下水と土壌水の酸素・水素安定同位体比の特徴について

It is necessary to make clear the formation process of the stable isotopic compositions of oxygen and hydrogen in soil water for consideration of the soil water movement. We have taken soil samples in the Terrestrial Environment Research Center (TERC) at eleven times from April 28 to November 15, 2001 and analyzed stable isotopic compositions of oxygen and hydrogen in soil water.There are cyclic variations of the δ18Ο and δD profiles in soil water. Isotopic compositions of soil water near soil surface become isotopically heavy because of the evaporation in particular summer season, thus the isotopic heavy peak is formed near the soil surface. In fall season, there is strongly rainfall by a number of typhoons and autumn rain fronts, so relatively large amount of precipitation are supplied to the soil. At that time, the cyclic variations of the isotopes in soil water move downward wholly, but when rainfall is relatively small amount, the cyclic variations do not move clearly. This result indicate that the recharge occurs only after intense rainfall events of typhoons or autumn rain front. And as a result of the stable isotopic compositions of soil water and groundwater, the piston flow is dominantly in the soil water movement in TERC. Consequently, cyclic variations of δ18Ο and δD in soil water are caused by the evaporation in summer season and transmitted downward by the storm events