Aging and Clonal Behavior of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. In this review, we summarize the current fate-mapping strategies that are used to track and visualize HSC clonal behavior during development or after stress. We then review the age-related changes in HSCs that can be inherited by daughter cells and act as a cellular memory to form functionally distinct clones. Altogether, we link aging of the hematopoietic system to HSC clonal evolution and discuss how HSC clones with myeloid skewing and low regenerative potential can be expanded during aging.     

Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis

Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.     

c-axis oriented ZnO formed in a rotating magnetic field with various rotation speeds

A rotating magnetic field was used to fabricate c-axis oriented zinc oxide. The influence of rotating speed on orientation structure was also examined. The aligned axes had the largest diamagnetic susceptibility, which axis was difficult to align with a static magnetic field. In c-axis oriented ZnO, the degree of orientation (Lotgering factor) in the green compact ranged from 0.2 to 0.5 along c-axis. The Lotgering factor increased with rotating speed. For all samples with the rotating magnetic field, the degrees of orientation increased up to above 0.9 after sintering at 1573 K.     

Star-shaped poly(lactic acid) with carboxylic acid terminal groups via poly-condensation

A series of star-shaped poly(lactic acid)s with carboxylic acid terminal groups have been synthesized by direct poly-condensation of lactic acid in the presence of a poly-carboxylic acid core molecule with triphenylphosphonium trifluoromethanesulfonate (TPP-T) catalyst.These star-polymers had thermal properties not very much different from those of star-shaped poly(lactic acid) with hydroxyl terminal groups and linear poly(lactic acid), irrespective of the structure of the core molecule and number of polymer arms. Solubility and degradability of these star-polymers were, however, greatly enhanced compared to those of star-polymers with hydroxyl terminal groups and increased depending on the number of polymer arms. From the star-shaped polymers, a variety of ammonium salts and the corresponding carboxyamides were successfully prepared.     

Numerical simulation of critical current performance in Nb3Sn strand subjected to periodic bending deformation

In the ITER Engineering Design Activity (EDA), four NB₃Sn model coils were developed and successfully tested. However, it was revealed that the critical current of the conductor degraded with the increase of electromagnetic force. One of the explanations of this phenomenon is a strand bending caused by enormous electromagnetic force. The authors therefore developed a simulation code using the distributed circuit model to investigate dependency of the critical current performance on the periodic bending deformation. The simulation results were in good agreement with the experiments. The dependence of the critical current on the periodic transverse load, temperature, periodic load pitch, thickness of Ta barrier which prevents Cu stabilizer from being contaminated by Sn, twist pitch of the strand, and RRR of the bronze matrix was investigated using the developed code. The results showed that the critical current degraded less with decreasing the pitch of the transverse load and increasing the Ta barrier thickness. It suggests that the shorter cabling pitch and the larger bending stiffness prevent the critical current degradation. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 171(3): 7–15, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20923     

Service‐level assurance in high‐availability multi‐unit systems using the M‐for‐N backup scheme

In this paper, we investigate service‐level assurance in high‐availability multi‐unit systems using the M‐for‐N backup scheme. M‐for‐N shared protection (backup) systems with priority control (i.e. prioritized protection switching and prioritized re‐housing of repaired units) can be applied to actual telecommunication devices that are subject to service‐level agreement (SLA) involving reliability measures. A priority level is assigned to each end user in such a system and the switching and unit re‐housing process is subject to the priority. The main contribution of this paper is to give a practical computation method of the user‐perceived availability under the priority control. Our case studies for real telecommunication systems reveal the effect of priority control on the user‐perceived availability. Copyright © 2011 John Wiley & Sons, Ltd.     

New technique for bonding hydroxyapatite ceramics and magnesium alloy by hydrothermal hot-pressing method

The solidification of hydroxyapatite (HA:Ca₁₀(PO₄)₆(OH)₂) and its bonding with Magnesium (Mg) alloys (AZ31; Mg–3Al–1Zn) were achieved simultaneously by using a hydrothermal hot-pressing method at a low temperature as low as 150 °C with no special surface treatment of Mg alloy. A mixture of calcium hydrogen phosphate dihydrate and calcium hydroxide was used as a starting powder material for solidifying HA. 3-point bending tests were conducted to obtain an estimate of the fracture toughness for the HA/Mg interface as well as for the HA ceramics only. The fracture toughness tests showed that the induced crack from the pre-crack tip deviated from the HA/Mg interface and propagated into the HA. The fracture toughness determined on the bonded HA/Mg specimen was close to that of the HA ceramics only (0.30 MPam^1/2).     

Behavior of composite segment for shield tunnel

Composite segment has been developed for obtaining high capacity in lining of shield tunnel subject to high hydraulic pressure and earth pressure in deep underground, which is made of steel plates connected to an infill of high fluidity concrete with shear connectors. However, a rational design method for composite segments can not be established, because the behavior of composite segments is not clarified. The purpose of this paper is to study the behavior of the most complicated composite segment with six steel plates using finite element method and the four-point bending tests. The effects of the shear studs and the thicknesses of steel plates were verified and estimated quantitatively. Meanwhile, the failure modes of composite segments were investigated. Comparisons show that the finite element model is suitable for composite segments and predicts the behavior of composite segments accurately.     

Biochip with integrated pumps for plug-based sequential exchange of solutions

A novel method for exchanging solutions used in biochemical analyses and a device to carry out the exchange are proposed. An array of plugs formed using six injectors was transported in a microflow channel using a main pump located at one end of the main flow channel. The injectors and main pump were operated on the basis of the change in volume caused by the electrolysis of water. Bubbles were produced from working electrodes; these bubbles caused a diaphragm placed below the injectors to inflate and occlude the inlet of the solution reservoir. Increase in the number of bubbles caused the reservoir to inject the solution into the main flow channel in the form of a plug. Each plug was individually transported downstream to the sensing area by the main pump, which was operated in a similar manner to the injector. The device was used for the detection of a tumor marker, α-fetoprotein (AFP). Plugs of necessary solutions were individually transported to the sensing area with immobilized primary antibodies to allow antigen–antibody binding, cleaning, and detection. The fluorescence intensity from the antibodies showed clear dependence on the concentration of AFP. The immobilization of antibodies could also be carried out on-chip.