A STRIPAK component Strip regulates neuronal morphogenesis by affecting microtubule stability

During neural development, regulation of microtubule stability is essential for proper morphogenesis of neurons. Recently, the striatin-interacting phosphatase and kinase (STRIPAK) complex was revealed to be involved in diverse cellular processes. However, there is little evidence that STRIPAK components regulate microtubule dynamics, especially in vivo. Here, we show that one of the core STRIPAK components, Strip, is required for microtubule organization during neuronal morphogenesis. Knockdown of Strip causes a decrease in the level of acetylated α-tubulin in Drosophila S2 cells, suggesting that Strip influences the stability of microtubules. We also found that Strip physically and genetically interacts with tubulin folding cofactor D (TBCD), an essential regulator of α- and β-tubulin heterodimers. Furthermore, we demonstrate the genetic interaction between strip and Down syndrome cell adhesion molecule (Dscam), a cell surface molecule that is known to work with TBCD. Thus, we propose that Strip regulates neuronal morphogenesis by affecting microtubule stability.This work was supported by grants from the Japanese Ministry of Education, Science, Sports, Culture and Technology (MEXT), the Japan Society for the Promotion of Science and the Japan Science and Technology Agency (to C.S., M.O., M.M. and T.C.)

Translocation of a daughter vesicle in a model system of self-reproducing vesicles

Translocation of a daughter vesicle from a mother vesicle through a pore is experimentally studied by many groups using a model system of self-reproducing vesicles. However, the theoretical formulation of the problem is not fully understood. In the present study, we present a theoretical formulation of the process based on our previous work [P. Khunpetch et al., Phys. Fluids 33, 077103 (2021)]. In our previous work, we considered the daughter vesicle as a rigid body. In the present work, however, we allow the daughter vesicle to deform during the expulsion process. We thus derive the free energy constituting of the elastic moduli of both the mother and daughter vesicles, and of pressure-driven contribution. The minimum energy path of the translocation is searched by using the string method. Our improved model successfully suggests the disappearance of the energy barrier where all the elastic moduli are in agreement with the experimental reports, while the previous work is unsuccessful to do so. The equations of motion of the daughter vesicle have been derived within the framework of the Onsager principle. We found that the translocation time of the daughter vesicle can be reduced when the pressure inside the mother vesicle increases, or the initial size of the daughter vesicle decreases

Morphologies in vesicle-vesicle adhesion

A single cell system, such as red blood cell, shows a series of shape transitions, stomatocyte-­‐discocyte-­‐ echinocyte, by applying a variety of chemical and physical stresses. This series of shapes is well described by minimization of elastic energy, i.e., area difference elasticity (ADE) model [1,2]. By adhering vesicles, the aggregates show rich morphologies due to the competition between the elastic energy and the adhesion energy, which gives physical basis of morphogenesis in cell division [3]. When two deformable spherical vesicles are adhered each other, the doublet has a flat contact area with two spherical caps (sphere doublet), where the total energy of the adhering vesicles is governed by the vesicle stretching energy and the adhesion energy. On the other hand, for the adhesion of non-­‐spherical vesicles, the membrane bending energy starts to compete the adhesion energy. In this region, the total energy of the doublet, W, is expressed by a sum of the vesicles’ bending energy, Wb,1 and Wb,2, and the adhesion energy assumed to be proportional to the contact area Ac, W = Wb,1 + Wb,2 − ΓAc , where Γ (\u3e0) is the adhesion strength and the bending energy is expressed by Helfrich model [4]. This theoretical model predicts that in the weak adhesion, the adhering vesicles prefer the minimum contact area morphology (flat adhesion), whereas in the strong adhesion, the doublet shows the maximum contact area morphology with curved interface [5]. This theoretical argument predicts fruitful morphology transitions of the doublets, although no systematic experiments have been reported so far. In this study we show the morphology transitions of adhering giant unilamellar vesicles (GUVs) induced by the changing the reduced volume of vesicles. The GUV is homogeneous single component vesicle composed of 1,2-­‐ dimyristoyl-­‐sn-­‐glycero-­‐3-­‐phosphocholine (DMPC). First we adhered two spherical GUVs with the aid of the depletion interaction. Thereafter we decreased the reduced volume of the adhering vesicles by using thermal expansion of membranes. Depending on the reduced volume, the doublet deformed its shape and showed a unique morphology transitions, sphere-­‐oblate-­‐prolate doublet and sphere-­‐sigmoidal doublet. We describe the observed morphology transitions based on the competition between the bending and the adhesion energies and explain the origin of the adhesion energy from the inter-­‐membrane interaction point of view. References [1] Bozic, B., Svetina, S., Zeks, B., and Waugh, R. E. (1992) Biophys. J., 61, 963. [2] Miao, L., Seifert, U., Wortis, M., and Döbereiner, H. G. (1994). Phys. Rev. E, 49, 5389. [3] Forgacs G., and Newman S. A. Biological physics of the developing embryo. Cambridge University Press, 2005. [4] Helfrich, W. (1973) Z. Naturforsch. C, 28, 693. [5] Ziherl, P., and Svetina, S. (2007) Proc. Natl. Acad. Sci. USA, 104, 761

Synthesis of Optically Active 2,3,6-Tri-O-benzyl-D-myo-inositol from D-Glucose

The title compound was synthesized from D-glucose as a key intermediate of D-Inositol-1,4,5-triphosphate synthesis without doing any optical resolution by utilizing C2 symmetry

Lipid membrane deformation in response to a local pH modification: theory and experiments

We study the deformation of a lipid membrane in response to a local pH modification. Experimentally, a basic solution is microinjected close to a giant unilamellar vesicle. A local deformation appears in the zone of the membrane that is closest to the micropipette, and relaxes when the injection is stopped. A theoretical description of this phenomenon is provided. It takes fully into account the spatiotemporal evolution of the concentration of hydroxide ions during and after the microinjection, as well as the linear dynamics of the membrane. This description applies to a local injection of any substance that reacts reversibly with the membrane lipids. We compare experimental data obtained in the domain of small deformations to the results of our linear description, and we obtain a good agreement between theory and experiments. In addition, we present direct experimental observations of the pH profile on the membrane during and after the microinjection, using pH-sensitive fluorescent lipids.Comment: 11 pages, 8 figure

Drosophila Strip serves as a platform for early endosome organization during axon elongation

Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.This work was supported by grants from the National Institute of General Medical Science of the National Institutes of Health (R01-GM085232 to V.I.G.), the National Institutes of Health (R01-DC005982 to L.L.), the Japanese Ministry of Education, Science, Sports, Culture, and Technology (MEXT), the Japan Society for the Promotion of Science, and the Japan Science and Technology Agency (to C.S., K.T., Y.Y., M.M., and T.C.)

Improved Neural Processing Efficiency in a Chronic Aphasia Patient Following Melodic Intonation Therapy: A Neuropsychological and Functional MRI Study

Melodic intonation therapy (MIT) is a treatment program for the rehabilitation of aphasic patients with speech production disorders. We report a case of severe chronic non-fluent aphasia unresponsive to several years of conventional therapy that showed a marked improvement following intensive nine-day training on the Japanese version of MIT (MIT-J). The purposes of this study were to verify the efficacy of MIT-J by functional assessment and examine associated changes in neural processing by functional magnetic resonance imaging. MIT improved language output and auditory comprehension, and decreased the response time for picture naming. Following MIT-J, an area of the right hemisphere was less activated on correct naming trials than compared to before training but similarly activated on incorrect trials. These results suggest that the aphasic symptoms of our patient were improved by increased neural processing efficiency and a concomitant decrease in cognitive load

Clinical Incidence of Sacroiliac Joint Arthritis and Pain after Sacropelvic Fixation for Spinal Deformity

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens