Takanobu Fukunaga

Evidence for osteocyte regulation of bone homeostasis through RANKL expression

Osteocytes embedded in bone have been postulated to orchestrate bone homeostasis by regulating both bone-forming osteoblasts and bone-resorbing osteoclasts. We find here that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ligand (RANKL) and have a greater capacity to support osteoclastogenesis in vitro than osteoblasts and bone marrow stromal cells. Furthermore, the severe osteopetrotic phenotype that we observe in mice lacking RANKL specifically in osteocytes indicates that osteocytes are the major source of RANKL in bone remodeling in vivo.

Blimp1-mediated repression of negative regulators is required for osteoclast differentiation.

Regulation of irreversible cell lineage commitment depends on a delicate balance between positive and negative regulators, which comprise a sophisticated network of transcription factors. Receptor activator of NF-κB ligand (RANKL) stimulates the differentiation of bone-resorbing osteoclasts through the induction of nuclear factor of activated T cells c1 (NFATc1), the essential transcription factor for osteoclastogenesis. Osteoclast-specific robust induction of NFATc1 is achieved through an autoamplification mechanism, in which NFATc1 is constantly activated by calcium signaling while the negative regulators of NFATc1 are suppressed. However, it has been unclear how such negative regulators are repressed during osteoclastogenesis. Here we show that B lymphocyte-induced maturation protein-1 (Blimp1; encoded by Prdm1), which is induced by RANKL through NFATc1 during osteoclastogenesis, functions as a transcriptional repressor of anti-osteoclastogenic genes such as Irf8 and Mafb. Overexpression of Blimp1 leads to an increase in osteoclast formation, and Prdm1-deficient osteoclast precursor cells do not undergo osteoclast differentiation efficiently. The importance of Blimp1 in bone homeostasis is underscored by the observation that mice with an osteoclast-specific deficiency in the Prdm1 gene exhibit a high bone mass phenotype caused by a decreased number of osteoclasts. Thus, NFATc1 choreographs the determination of cell fate in the osteoclast lineage by inducing the repression of negative regulators as well as through its effect on positive regulators.

In-situ measurement of the heat transport in defect- engineered free-standing single-layer graphene

Utilizing nanomachining technologies, it is possible to manipulate the heat transport in graphene by introducing different defects. However, due to the difficulty in suspending large-area single-layer graphene (SLG) and limited temperature sensitivity of the present probing methods, the correlation between the defects and thermal conductivity of SLG is still unclear. In this work, we developed a new method for fabricating micro-sized suspended SLG. Subsequently, a focused ion beam (FIB) was used to create nanohole defects in SLG and tune the heat transport. The thermal conductivity of the same SLG before and after FIB radiation was measured using a novel T-type sensor method on site in a dual-beam system. The nanohole defects decreased the thermal conductivity by about 42%. It was found that the smaller width and edge scrolling also had significant restriction on the thermal conductivity of SLG. Based on the calculation results through a lattice dynamics theory, the increase of edge roughness and stronger scattering on long-wavelength acoustic phonons are the main reasons for the reduction in thermal conductivity. This work provides reliable data for understanding the heat transport in a defective SLG membrane, which could help on the future design of graphene-based electrothermal devices.

Spontaneous magnetoencephalography alpha rhythm measurement in a cylindrical magnetic shield employing magnetic shaking

This article shows a demonstration of magnetoencephalography measurement in a cylindrical magnetic shield made of cobalt-based amorphous tape with magnetic shaking. The noise levels of the first-order superconducting quantum interference device gradiometers that operated in the shield were reduced to as low as 40 fT/√Hz at 10 Hz by surrounding it with a simple rf shield made of conductive cloth. We observed spontaneous alpha rhythms from a human brain in this shielding system. Alpha rhythms and their suppression caused by opening the eyes were clearly found, which was also confirmed by electroencephalography measurement from the same volunteer under similar conditions.

Simultaneous measurement of electrical and thermal conductivities of suspended monolayer graphene

We measured both in-plane electrical and thermal properties of the same suspended monolayer graphene using a novel T-type sensor method. At room temperature, the values are about 240 000 Ω−1 m−1 and 2100 W m−1 K−1 for the electrical and thermal conductivities, respectively. Based on the Wiedemann-Franz law, the electrons have negligible contribution to the thermal conductivity of graphene, while the in-plane LA and TA modes phonons are the dominant heat carriers. In monolayer graphene, the absence of layer-layer and layer-substrate interactions enhances the contribution of long wave-length phonons to the heat transport and increases the thermal conductivity accordingly. The reported method and experimental data of suspended monolayer graphene are useful for understanding the basic physics and designing the future graphene electronic devices.

Effect of irreversible electroporation on three-dimensional cell culture model

Irreversible electroporation (IRE) is a new treatment to necrotize abnormal cells by high electric pulses. Electric potential difference over 1 V across the plasma membrane permanently permeabilizes the cell with keeping the extracellular matrix intact if the thermal damage due to the Joule heating effect is avoided. This is the largest advantage of the IRE compared to the other conventional treatment. However, since the IRE has just started to be used in clinical tests, it is important to predict the necrotized region that depends on pulse parameters and electrode arrangement. We therefore examined the numerical solution to the Laplace equation for the static electric field to predict the IRE-induced cell necrosis. Three-dimensionally (3-D) cultured cells in a tissue phantom were experimentally subjected to the electric pulses through a pair of puncture electrodes. The necrotized area was determined as a function of the pulse repetition and compared with the area that was estimated by the numerical analysis.

Effect of gas flow on the temperature rise of a micro-beam-type thermal conductivity detector

We have proposed a “micro-beam” MEMS sensor for measuring the thermal conductivity of gases and liquids. It is a beam-shaped metallic foil sensor, approximately 10 μm in length, that is built over a trench on a silicon substrate. The principle of the measurement is to determine the thermal conductivity of a sample from the temperature rise of the sensor at a steady state, which is achieved within a millisecond. Potential application of the sensor would be gas sensors and gas chromatography, where the sensor is exposed to a gas flow. Hence the objective of the present study is to examine the effect of flow on the temperature of the sensor.A chip with a platinum sensor fabricated on its surface was embedded in a flat PVC plate and placed in the potential core of an air flow from a nozzle. The electrical resistance of the sensor was measured by a four-wire technique with heating the sensor with DC current. The results showed that the temperature rise at a given heating rate, which indicates the heat dissipating potential to the air, did not change with increasing the air velocity. It also agreed well each other irrespective of the angle of attack or the length from the leading edge. The results demonstrated that the temperature rise of the sensor was independent of the air flow, suggesting that the heat dissipation was governed only by the heat conduction to the air.© 2013 ASME