Comprehensive Analysis of Oligo/Polysialylglycoconjugates in Cancer Cell Lines

In cancer cells, cell-surface sialylation is altered, including a change in oligo/polysialic acid (oligo/polySia) structures. Since they are unique and rarely expressed in normal cells, oligo/polySia structures may serve as promising novel biomarkers and targets for therapies. For the diagnosis and treatment of the disease, a precise understanding of the oligo/polySia structures in cancer cells is necessary. In this study, flow cytometric analysis and gene expression datasets were obtained from sixteen different cancer cell lines. These datasets demonstrated the ability to predict glycan structures and their sialylation status. Our results also revealed that sialylation patterns are unique to each cancer cell line. Thus, we can suggest promising combinations of antibody and cancer cell for glycan prediction. However, the precise prediction of minor glycans need to be further explored.     

Hematopoietic–Mesenchymal Signals Regulate the Properties of Mesenchymal Stem Cells

It is well known that the properties of hematopoietic stem/progenitor cells (HSCs), such as their self-renewal ability and multipotency, are maintained through interactions with mesenchymal stem/stromal cells (MSCs). MSCs are rare cells that are present in the bone marrow and are useful for clinical applications due to their functional ability. To obtain the necessary number of cells, MSCs must be cultured to expand, but this causes a remarkable decrease in stem cell properties, such as multipotency and proliferation ability. In this study, we show that the c-Mpl signal, which is related to the maintenance of hematopoietic stem cells, has an important effect on the proliferation and differentiation ability of MSCs. Utilizing a co-culture system comprising MSCs and HSCs, it is suggested that signaling from hematopoietic cells to MSCs supports cell proliferation. Interestingly, the enhanced proliferation ability of the HSCs was decreased in c-Mpl knock-out HSCs (c-Mpl-KO). In addition, the MSCs co-cultured with c-Mpl-KO HSCs had reduced MSC marker expression (PDGFRa and Sca-1) compared to the MSCs co-cultured with c-Mpl-wild-type HSCs. These results suggest that a hematopoietic–mesenchymal signal exists, and that the state of the HSCs is important for the stability of MSC properties.     

Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate,Fenofibric Acid,and Pemafibrate

Among the agonists against three peroxisome proliferator-activated receptor (PPAR) subtypes, those against PPARα (fibrates) and PPARγ (glitazones) are currently used to treat dyslipidemia and type 2 diabetes, respectively, whereas PPARδ agonists are expected to be the next-generation metabolic disease drug. In addition, some dual/pan PPAR agonists are currently being investigated via clinical trials as one of the first curative drugs against nonalcoholic fatty liver disease (NAFLD). Because PPARα/δ/γ share considerable amino acid identity and three-dimensional structures, especially in ligand-binding domains (LBDs), clinically approved fibrates, such as bezafibrate, fenofibric acid, and pemafibrate, could also act on PPARδ/γ when used as anti-NAFLD drugs. Therefore, this study examined their PPARα/δ/γ selectivity using three independent assays—a dual luciferase-based GAL4 transactivation assay for COS-7 cells, time-resolved fluorescence resonance energy transfer-based coactivator recruitment assay, and circular dichroism spectroscopy-based thermostability assay. Although the efficacy and efficiency highly varied between agonists, assay types, and PPAR subtypes, the three fibrates, except fenofibric acid that did not affect PPARδ-mediated transactivation and coactivator recruitment, activated all PPAR subtypes in those assays. Furthermore, we aimed to obtain cocrystal structures of PPARδ/γ-LBD and the three fibrates via X-ray diffraction and versatile crystallization methods, which we recently used to obtain 34 structures of PPARα-LBD cocrystallized with 17 ligands, including the fibrates. We herein reveal five novel high-resolution structures of PPARδ/γ–bezafibrate, PPARγ–fenofibric acid, and PPARδ/γ–pemafibrate, thereby providing the molecular basis for their application beyond dyslipidemia treatment.     

Microstructure of Aluminum/Glass Joint Bonded by Ultrasonic Wire Welding

An Al/glass joint created by using ultrasonic welding was analyzed by means of multiscale observation techniques. A cross-sectional analysis of the microstructure revealed that a directly joined interface without reaction phases formed at the periphery of a round joined region. The size of Al grains markedly decreased after ultrasonic welding and some subgrains were observed along the interface. The finer Al grains observed around the periphery of the joined interface showed active plastic flow that promoted welding.     

Finite Element Analysis of Precursors to Macroscopic Stick–Slip Motion in Elastic Materials: Analysis of Friction Test as a Boundary Value Problem

In this study, we apply the finite element method to investigate precursor to frictional sliding phenomena arising immediately prior to macroscopic stick–slip transitions in elastic bodies within the framework of a continuum theory. Using a numerical model that mimics an actual experimental system, we study the behavior of contact surface nodes to assess the influence of stiffness, driving velocity, initial conditions, and discretization conditions on the propagation characteristics of microscopic slips. In particular, we show that the initial distribution of frictional stress arising due to the Poisson effect has a significant effect on the propagation characteristics in slip regions. Next, based on the results of a finite element analysis of precursor phenomena that accounts for the influence of bulk compliance, we consider the determination of parameters in rate-dependent friction models. With regard to the behavior of sliding friction, we show that the relationship between friction tests and friction models is fundamentally different from the relationship between material tests and constitutive models for material deformation. We conclude that a proper understanding and classification of friction tests, friction models, and the relationship between these tests and boundary value problems are crucial ingredients in the application of computer-aided engineering techniques to sliding-friction phenomena; indeed, friction tests must ultimately be treated as boundary value problems.     

Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.     

InxGa1−xAs ohmic contacts to n-type GaAs with a tungsten nitride barrier

Significant reduction of the contact resistance of In_0.7Ga_0.3As/Ni/W contacts (which were previously developed by sputtering in our laboratory) was achieved by depositing a W₂N barrier layer between the Ni layer and W layer. The In_0.7Ga_0.3 As/Ni/W₂N/W contact prepared by the radio-frequency sputtering technique showed the lowest contact resistance of 0.2 Ωmm after annealing at 550°C for 10 s. This contact also provided a smooth surface, good reproducibility, and excellent thermal stability at 400°C. The polycrystalline W₂N layer was found to suppress the In diffusion to the contact surface, leading to improvement of the surface morphology and an increase in the total area of the In_xGa−As between metal and the GaAs substrate. These improvements are believed to reduce the contact resistance.     

Characterisation of optically driven microstructures for manipulating single DNA molecules under a fluorescence microscope

Optical tweezers are powerful tools for manipulating single DNA molecules using fluorescence microscopy, particularly in nanotechnology‐based DNA analysis. We previously proposed a manipulation technique using microstructures driven by optical tweezers that allows the handling of single giant DNA molecules of millimetre length that cannot be manipulated by conventional techniques. To further develop this technique, the authors characterised the microstructures quantitatively from the view point of fabrication and efficiency of DNA manipulation under a fluorescence microscope. The success rate and precision of the fabrications were evaluated. The results indicate that the microstructures are obtained in an aqueous solution with a precision ∼50 nm at concentrations in the order of 10⁶ particles/ml. The visibility of these microstructures under a fluorescence microscope was also characterised, along with the elucidation of the fabrication parameters needed to fine tune visibility. Manipulating yeast chromosomal DNA molecules with the microstructures illustrated the relationship between the efficiency of manipulation and the geometrical shape of the microstructure. This report provides the guidelines for designing microstructures used in single DNA molecule analysis based on on‐site DNA manipulation, and is expected to broaden the applications of this technique in the future.Inspec keywords: DNA, molecular biophysics, fluorescence, optical microscopy, radiation pressure, biological techniquesOther keywords: optically driven microstructures, single DNA molecule analysis, fluorescence microscopy, optical tweezers, nanotechnology‐based DNA analysis, manipulation technique, aqueous solution, fine tune visibility, yeast chromosomal DNA molecules, geometrical shape, on‐site DNA manipulation     

An innovative modularity of heat circulation for fractional distillation

A novel modularity of heat circulation for distillation process, which reduces the energy consumption, is proposed. By incorporating compressors and heat exchangers, the heat of the distillate is recuperated and exchanged with the heat of the feed streams. The proposed technology achieves the reduction in the required energy more than 75% as compared with a benchmark process which uses external heat source for heating. This shows the proposed modularity of heat circulation for distillation process is very promising technology to drastically reduce energy demand for distillation.