Osteoprotegerinはcollagen生合成と血管平滑筋の増殖を促す事で脳動脈瘤の増大を抑制する

京都大学新制・課程博士博士(医学)甲第23380号医博第4749号京都大学大学院医学研究科医学専攻(主査)教授 山下 潤, 教授 木村 剛, 教授 YOUSSEFIAN Shohab学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Effect of minor loop on magnetic characteristics of permanent magnet type of MRI

A modeling technique of the minor loop using typical hysteresis loops is shown. The effect of the minor loop and eddy current in the pole piece of a permanent magnet type of MRI on the residual flux density of the probe coil is examined. It is illustrated that the change &#916;B of residual flux density occurs due to the minor loop of the pole piece. It is also pointed out that the choice of time interval &#916;t is important in a nonlinear analysis considering the minor loop</p

Real-time atomic-resolution imaging of crystal growth process in water by phase modulation atomic force microscopy at one frame per second

Recent advancement in dynamic-mode atomic force microscopy (AFM) has enabled its operation in liquid with atomic-scale resolution. However, its imaging speed has often been too slow to visualize atomic-scale dynamic processes. Here, we propose a method for making a significant improvement in the operation speed of dynamic-mode AFM. In this method, we use a wideband and low-latency phase detector with an improved algorithm for the signal complexification. We demonstrate atomic-scale imaging of a calcite crystal growth process in water at one frame per second. The significant improvement in the imaging speed should enable various studies on unexplored atomic-scale interfacial processes. © 2013 AIP Publishing LLC

Ion-specific nanoscale compaction of cysteine-modified poly(acrylic acid) brushes revealed by 3D scanning force microscopy with frequency modulation detection

Stimuli-responsive polyelectrolyte brushes adapt their physico-chemical properties according to pH and ion concentrations of the solution in contact. We synthesized a poly(acrylic acid) bearing cysteine residues at side chains and a lipid head group at the terminal, and incorporated them into a phospholipid monolayer deposited on a hydrophobic silane monolayer. The ion-specific, nanoscale response of polyelectrolyte brushes was detected by using three-dimensional scanning force microscopy (3D-SFM) combined with frequency modulation detection. The obtained topographic and mechanical landscapes indicated that the brushes were uniformly stretched, undergoing a gradual transition from the brush to the bulk electrolyte in the absence of divalent cations. When 1 mM calcium ions were added, the brushes were uniformly compacted, exhibiting a sharper brush-to-bulk transition. Remarkably, the addition of 1 mM cadmium ions made the brush surface significantly rough and the mechanical landscape highly heterogeneous. Currently, cadmium-specific nanoscale compaction of the brushes is attributed to the coordination of thiol and carboxyl side chains with cadmium ions, as suggested for naturally occurring, heavy metal binding proteins

Chotosan (Diaoteng San)-induced improvement of cognitive deficits in senescence-accelerated mouse (SAMP8) involves the amelioration of angiogenic/neurotrophic factors and neuroplasticity systems in the brain

<p>Abstract</p> <p>Background</p> <p>Chotosan (CTS, <it>Diaoteng San</it>), a Kampo medicine (<it>ie </it>Chinese medicine) formula, is reportedly effective in the treatment of patients with cerebral ischemic insults. This study aims to evaluate the therapeutic potential of CTS in cognitive deficits and investigates the effects and molecular mechanism(s) of CTS on learning and memory deficits and emotional abnormality in an animal aging model, namely 20-week-old senescence-accelerated prone mice (SAMP8), with and without a transient ischemic insult (T2VO).</p> <p>Methods</p> <p>Age-matched senescence-resistant inbred strain mice (SAMR1) were used as control. SAMP8 received T2VO (T2VO-SAMP8) or sham operation (sham-SAMP8) at day 0. These SAMP8 groups were administered CTS (750 mg/kg, p.o.) or water daily for three weeks from day 3.</p> <p>Results</p> <p>Compared with the control group, both sham-SAMP8 and T2VO-SAMP8 groups exhibited cognitive deficits in the object discrimination and water maze tests and emotional abnormality in the elevated plus maze test. T2VO significantly exacerbated spatial cognitive deficits of SAMP8 elucidated by the water maze test. CTS administration ameliorated the cognitive deficits and emotional abnormality of sham- and T2VO-SAMP8 groups. Western blotting and immunohistochemical studies revealed a marked decrease in the levels of phosphorylated forms of neuroplasticity-related proteins, N-methyl-D-aspartate receptor 1 (NMDAR1), Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), cyclic AMP responsive element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the frontal cortices of sham-SAMP8 and T2VO-SAMP8. Moreover, these animal groups showed significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2 (VEGFR2), platelet-derived growth factor-A (PDGF-A) and PDGF receptor α (PDGFRα). CTS treatment reversed the expression levels of these factors down-regulated in the brains of sham- and T2VO-SAMP8.</p> <p>Conclusion</p> <p>Recovery of impaired neuroplasticity system and VEGF/PDGF systems may play a role in the ameliorative effects of CTS on cognitive dysfunction caused by aging and ischemic insult.</p

Lactophorin in Camel Milk Undergoing Specific Proteolysis and Exhibiting Potent Anticancer Action against Human Colon and Breast Cancer Cells Through ROS Generation

Background: Camel milk has been recognized for its health benefits since ancient times and has recently been attracting increasing attention as a form of medical treatment for diverse human diseases. Studies on the health benefits of camel milk attributed its medicinal effects to nutritional status, but the molecular mechanisms of proteins involved in such effects remain unknown. Objectives: The aim of this study was to explore the anticancer properties of camel milk proteins (CMPs). Methods: CMPs were fractionated into camel casein proteins (CCPs) and camel whey proteins (CWPs). The CWP exhibited the most potent anticancer activity against colon (HCT-116) and breast (MCF-7) cancer cells. The CWP was further fractionated into cationic and anionic proteins using HiTrap cationic (SP-XL) and anionic (QFF) exchange columns. Results: QFF-bound proteins (QFF-B) exhibited the strongest anticancer activities against both cancer cells. QFF-B proteins produced three peaks (P1~P3) on RP-HPLC, whereas P3 showed superior anticancer activity. The cytotoxic effects of CWP and QFF-B proteins are associated with increased production of intracellular ROS and subsequent apoptosis in both cancer cells. MALDI-TOF-MS identified lactophorin, glycation-dependent cell adhesion molecule1 (GlyCAM-1), and its three driven fragments as dominant peptides in QFF-B, while RP-HPLC-P3 contained two of them with molecular masses of 8080.3 and 9395.6 Da. The two peptides, both derived from the C-terminal of lactophorin, were the most representative peptides in the most active protein fractions (QFF-B and RP-HPLC-P3). Conclusion: The results highlight for the first time that lactophorin is the major anti-cancer ingredient in camel milk and its unique C-terminal peptides present potential candidacy as anticancer agents in nutraceutical and pharmacological applications

Note: High-speed Z tip scanner with screw cantilever holding mechanism for atomic-resolution atomic force microscopy in liquid

High-speed atomic force microscopy has attracted much attention due to its unique capability of visualizing nanoscale dynamic processes at a solid/liquid interface. However, its usability and resolution have yet to be improved. As one of the solutions for this issue, here we present a design of a high-speed Z-tip scanner with screw holding mechanism. We perform detailed comparison between designs with different actuator size and screw arrangement by finite element analysis. Based on the design giving the best performance, we have developed a Z tip scanner and measured its performance. The measured frequency response of the scanner shows a flat response up to ∼10 kHz. This high frequency response allows us to achieve wideband tip-sample distance regulation. We demonstrate the applicability of the scanner to high-speed atomic-resolution imaging by visualizing atomic-scale calcite crystal dissolution process in water at 2 s/frame