Application of Chondroitin Sulfate Derivatives for Understanding Axonal Guidance in the Nervous System during Development

Neuronal axons and their growth cones recognize molecular guidance cues within the local environment, forming axonal pathways to produce precise neuronal networks during nervous system development. Chondroitin sulfates (CS), carbohydrate chains on chondroitin sulfate proteoglycans, exhibit great structural diversity and exert various influences on axons and growth cones as guidance cues or their modulators; however, the relationship between their structural diversity and function in axonal guidance is not well known. To uncover the roles of CS in axonal guidance, artificially modified hybrid molecules: CS derivatives of biotinylated CS and lipid-derivatized CS, were used.The experiments with biotinylated CS suggest that the growing axons act on their environment, modifying CS, and rendering it more favorable for their growth. The experiments with lipid-derivatized CS demonstrated that growth cones distinguish types of CS with different unit contents and are likely to discriminate the structural diversity of CS.The application of CS derivatives is useful in uncovering axon–environment interaction and structure–function relationship of CS directly

Moderate repulsive effects of E-unit-containing chondroitin sulfate (CSE) on behavior of retinal growth cones

Chondroitin sulfate (CS), the carbohydrate chain of chondroitin sulfate proteoglycans, is involved in neuronal circuit formation during development. CS shows great structural diversity with combination of disaccharide units of different structure (A-, C-, D-, or Eunit).However, whether its structural diversity contributes to pathway formation remains unclear. We chemically coupled the reducing end of various types of CS to the amino group of phosphatidylethanolamine (lipid-derivatized CS, CS-PE) and established an in vitro time-lapse assay to observe the behaviors of growth cones of retinal ganglion cells from embryonic day 6 chick retina on exposure to beads coated with lipid-derivatized CS (CS-PE beads). Among CS-PEs with different content of the structural units, the beads coated with E-unit–containing CS-PE [E-unit: GlcAβ1-3GalNAc(4,6-O-disulfate)] (CSE-PE beads) significantly caused the growth cones to retract and to turn away from the beads, but the beads coated with CSA-, CSC- or CSDPE beads did not. Importantly, not all the growth cones retracted equally from the CSE-PE beads, but they showed continuum of the repulsive behaviors; some behaved moderately and others remarkably. The growth cones distinguished different samples of CS: CSE and the others. Moreover, the continuum of the repulsive behaviors suggests that CS might be involved with the fine regulation of growth cones\u27 behavior through its characteristic structure

Current Topics of Microwave EMI Antennas and Measurements

This paper reviews recent developments in small-sized broadband antennas for EMI measurements, especially in the microwave frequency region. Transient EMI measurements are also discussed by introducing complex antenna factors and conversion of frequency-domain data into time-domain data. This paper also focuses on considerable improvements achieved in calibration techniques for conventional EMI antennas in VHF/UHF bands

Big-Volume SliceGAN for Improving a Synthetic 3D Microstructure Image of Additive-Manufactured TYPE 316L Steel

A modified SliceGAN architecture was proposed to generate a high-quality synthetic three-dimensional (3D) microstructure image of TYPE 316L material manufactured through additive methods. The quality of the resulting 3D image was evaluated using an auto-correlation function, and it was discovered that maintaining a high resolution while doubling the training image size was crucial in creating a more realistic synthetic 3D image. To meet this requirement, modified 3D image generator and critic architecture was developed within the SliceGAN framework.Sugiura K., Ogawa T., Adachi Y., et al. Big-Volume SliceGAN for Improving a Synthetic 3D Microstructure Image of Additive-Manufactured TYPE 316L Steel. Journal of Imaging 9, 90 (2023); https://doi.org/10.3390/jimaging9050090

Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting

In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM) enabled biosensor technology. We analysed the interaction between the rVAR2 protein and its placental-like chondroitin sulfate (pl-CS) receptor in primary human placenta tissue and in breast and prostate tumour specimens in situ. rVAR2 interacted with FFPE human placenta and cancer tissue with an affinity in the nanomolar range, and showed no detectable interaction with pl-CS negative normal tissue. We further validated the method by including analysis with the androgen receptor N-20 antibody (anti-AR). As the KD value produced by this method is independent of the number of epitopes available, this readout offers a quantitative and unbiased readout for in situ binding-avidity and amount of binding epitopes. In summary, this method adds a new and important dimension to classical IHC-based molecular pathology by adding information about the binding characteristics in biologically relevant conditions. This can potentially be used to select optimal biologics for diagnostic and for therapeutic applications as well as guide the development of novel high affinity binding drugs. Keywords: Quartz crystal microscale, Biomarker, Biosensor, VAR2CSA, Cancer, Malari

Structure of MSPL–inhibitor complex

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19

食道再建用胃管に発生する血行障害の原因としての迷走神経切断とその対策としての交感神経遮断術について

京都大学0048新制・論文博士医学博士論医博第302号新制||医||106(附属図書館)1386(主査)教授 木村 忠司, 教授 半田 肇, 教授 本庄 一夫学位規則第5条第2項該当Kyoto UniversityDA

食道再建用胃管に発生する血行障害の原因としての迷走神経切断とその対策としての交感神経遮断術について

京都大学0048新制・論文博士医学博士論医博第302号新制||医||106(附属図書館)1386(主査)教授 木村 忠司, 教授 半田 肇, 教授 本庄 一夫学位規則第5条第2項該当Kyoto UniversityDA

Male replacement and stability of territorial boundary in a group of agile gibbons (Hylobates agilis agilis) in West Sumatra, Indonesia.

We report membership change in a group of wild agile gibbons, Hylobates agilis agilis, in West Sumatra, Indonesia. During 6-month observational periods, we focused on a particular unit of individuals known as the B group. We confirmed that the group consisted of five individuals: one adult female, one adult male, one subadult male, one subadult female, and one infant male. During our observations, the resident adult male and the two subadult individuals dispersed or disappeared, and a new adult male took over the group. We examined the effects of the male replacement on the territorial boundary, using the auditory census technique. The boundary was stable. We also documented the succession of the home range. Our results indicate a flexible social structure in this species and contribute some useful data to an ongoing debate on their social dynamics