Increased leukocyte aggregates are associated with atherosclerosis in patients with hemodialysis

Little data are available on the role of blood rheology in atherosclerosis in hemodialysis (HD) patients. This study sought to assess the relationship between leukocytes conjugated with platelets (leukocyte aggregates [LA]) and atherosclerosis in patients with HD. The present study included 118 patients on HD. As surrogate markers of atherosclerosis, aortic stiffness measured by brachial-ankle pulse wave velocity, and carotid intima-media thickness (IMT) were measured. As an assessment of LA, a method, microchannel array flow analyzer, which makes it possible to directly observe the flow of blood cell elements through the microchannel, was used. We measured a number of LA during 50 μL flow of whole blood through microchannels. In 12 age-matched healthy individuals, a number of LA during 50 μL flow of whole blood was 25.7±5.4, whereas in HD patients it was significantly increased up to 48.2±16.4 (P<0.001). Flow cytometry demonstrated that LA were predominantly monocytes. Leukocyte aggregates were positively associated with plasma levels of fibrinogen (P<0.01), or serum high-sensitive C-reactive protein (P<0.01). Moreover, LA had highly significant associations with brachial-ankle pulse wave velocity (P<0.001) and IMT (P<0.001). In conclusion, we demonstrated hemorheologically that monocyte-platelet conjugates play an important role in aortic stiffness and IMT in HD patients.     

Planning in human children (Homo sapiens) assessed by maze problems on the touch screen.

The authors examined how human children perform on maze tasks on the touch screen and whether the children plan the solution of the mazes. In Experiment 1, the authors exposed children around 3 years of age to a maze having an L-shaped line as a barrier that can be solved by moving an illustration of a dog (the target) to that of a bone (the goal) with their fingers. The participants successfully solved the maze by taking efficient routes more frequently than chance, although the authors found no evidence that a preview of the maze before starting to solve the task facilitated their performance. In Experiment 2, using a plus-shaped maze, the authors found that 3- and 4-year-old children plan and adjust their moves while solving the maze, with 4-year-olds showing more advanced and higher-level planning than 3-year-olds. Similarity of these results to what the authors previously found in pigeons tested in the same tasks may suggest an analogy for planning capacity in the behavioral level across taxa and developmental stages. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Out‐of‐Plane Strain Induced in a Moiré Superstructure of Monolayer MoS2 and MoSe2 on Au(111)

Making contact of transition metal dichalcogenides (TMDCs) with a metal surface is essential for fabricating and designing electronic devices and catalytic systems. It also generates strain in the TMDCs that plays significant role in both electronic and phonon structures. Therefore, detailed understanding of mechanism of the strain generation is important to fully comprehend the modulation effect for the electronic and phonon properties. Here, MoS₂ and MoSe₂ monolayers are grown on Au surface by chemical vapor deposition and it is demonstrated that the contact with a crystalline Au(111) surface gives rise to only out‐of‐plane strain in both MoS₂ and MoSe₂ layers, whereas no strain generation is observed on polycrystalline Au or SiO₂/Si surfaces. Scanning tunneling microscopy analysis provides information regarding consequent specific adsorption sites between lower S (Se) atoms in the S? Mo? S (Se? Mo? Se) structure and Au atoms via unique moiré superstructure formation for MoS₂ and MoSe₂ layers on Au(111). This observation indicates that the specific adsorption sites give rise to out‐of‐plane strain in the TMDC layers. Furthermore, it also leads to effective modulation of the electronic structure of the MoS₂ or MoSe₂ layer.     

Effect of Compressive Stress in Tumor Microenvironment on Malignant Tumor Spheroid Invasion Process

In this study, we proposed an in vitro tumor model to simulate the mechanical microenvironment and investigate the effect of compressive stress on the invasion process of malignant tumors. It has been pointed out that the biomechanical environment, as well as the biochemical environment, could affect the transformation of cancer cell migration, invasion, and metastasis. We hypothesized that the solid stress caused by the exclusion of surrounding tissue could transform tumor cells from noninvasive to invasive phenotypes. Colorectal cell spheroids were embedded and cultured in agarose gels of varying concentrations to simulate the earliest stages of tumor formation and invasion. The spheroids embedded in gels at higher concentrations showed peculiar growth after 72 h of culture, and the external compressive loading imposed on them caused peculiar growth even in the gels at lower concentrations. In conclusion, the mechanical microenvironment caused the transformation of tumor cell phenotypes, promoting the growth and invasion of tumor cell spheroids.     

Aesthetic Rating and Color Suggestion for Color Palettes

A model to rate color combinations that considers human aesthetic preferences is proposed. The proposed method does not assume that a color palette has a specific number of colors, i.e., input is not restricted to a two‐, three‐, or five‐color palettes. We extract features from a color palette whose size does not depend on the number of colors in the palette. The proposed rating prediction model is trained using a human color preference dataset. The model allows a user to extend a color palette, e.g., from three colors to five or seven colors, while retaining color harmony. In addition, we present a color search scheme for a given palette and a customized version of the proposed model for a specific color tone. We demonstrate that the proposed model can also be applied to various palette‐based applications.     

Completely Chemically Synthesized Long DNA Can be Transcribed in Human Cells

Chemical ligation reaction of DNA is useful for the construction of long functional DNA using oligonucleotide fragments that are prepared by solid phase chemical synthesis. However, the unnatural linkage structure formed by the ligation reaction generally impairs the biological function of the resulting ligated DNA. We achieved the complete chemical synthesis of 78 and 258 bp synthetic DNAs via multiple chemical ligation reactions with phosphorothioate and haloacyl-modified DNA fragments. The latter synthetic DNA, coding shRNA for luciferase genes with a designed truncated SV promoter sequence, successfully induced the expected gene silencing effect in HeLa cells.     

Blood–Nerve Barrier (BNB) Pathology in Diabetic Peripheral Neuropathy and In Vitro Human BNB Model

In diabetic peripheral neuropathy (DPN), metabolic disorder by hyperglycemia progresses in peripheral nerves. In addition to the direct damage to peripheral neural axons, the homeostatic mechanism of peripheral nerves is disrupted by dysfunction of the blood–nerve barrier (BNB) and Schwann cells. The disruption of the BNB, which is a crucial factor in DPN development and exacerbation, causes axonal degeneration via various pathways. Although many reports revealed that hyperglycemia and other important factors, such as dyslipidemia-induced dysfunction of Schwann cells, contributed to DPN, the molecular mechanisms underlying BNB disruption have not been sufficiently elucidated, mainly because of the lack of in vitro studies owing to difficulties in establishing human cell lines from vascular endothelial cells and pericytes that form the BNB. We have developed, for the first time, temperature-sensitive immortalized cell lines of vascular endothelial cells and pericytes originating from the BNB of human sciatic nerves, and we have elucidated the disruption to the BNB mainly in response to advanced glycation end products in DPN. Recently, we succeeded in developing an in vitro BNB model to reflect the anatomical characteristics of the BNB using cell sheet engineering, and we established immortalized cell lines originating from the human BNB. In this article, we review the pathologic evidence of the pathology of DPN in terms of BNB disruption, and we introduce the current in vitro BNB models.     

Conformational changes in the A1 domain of von Willebrand factor modulating the interaction with platelet glycoprotein Ibalpha

The interaction between von Willebrand factor (vWF) A1 domain and platelet glycoprotein Ib alpha occurs in the presence of high shear stress or when vWF becomes immobilized onto a surface but not appreciably in the normal circulation. To investigate the structural properties regulating A1 domain function, we have used recombinant fragments prepared either in cyclic form with oxidized Cys509-Cys695 disulfide bond or reduced and alkylated. Interaction with glycoprotein Ibalpha was assessed by testing inhibition of monoclonal antibody LJ-Ib1 binding to platelets and inhibition of shear-induced platelet aggregation mediated by native vWF. Fragments exposed to pH between 2.5 and 3.5 adopted the molten globule conformation with loosened tertiary structure intermediate between native and completely unordered state. Maximal receptor binding activity was observed when fragments kept at acidic pH, particularly after reduction of the Cys509-Cys695 disulfide bond, were subjected to quick refolding by rapid pH increase. In contrast, slow refolding by incremental pH change over several hours resulted in at least 20-fold lower activity. A specific single point mutation (I546V) resulted in enhanced receptor binding, whereas another mutation (S561G) caused markedly reduced binding. These results provide experimental evidence that conformational transitions can modulate function of the vWF A1 domain in solution.