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Microscale needle-like electrode technologies offer in vivoextracellular recording with a high spatiotemporal resolution. Further miniaturization of needles to nanoscale minimizes tissue injuries; however, a reduced electrode area increases electrical impedance that degrades the quality of neuronal signal recording. We overcome this limitation by fabricating a 300 nm tip diameter and 200 μm long needle electrode where the amplitude gain with a high-impedance electrode (>15 MΩ, 1 kHz) was improved from 0.54 (−5.4 dB) to 0.89 (−1.0 dB) by stacking it on an amplifier module of source follower. The nanoelectrode provided the recording of both local field potential (<300 Hz) and action potential (>500 Hz) in the mouse cortex, in contrast to the electrode without the amplifier. These results suggest that microelectrodes can be further minimized by the proposed amplifier configuration for low-invasive recording and electrophysiological studies in submicron areas in tissues, such as dendrites and axons.

We made observations of magnetic field variations in association with pulsating auroras with the magneto‐impedance sensor magnetometer (MIM) carried by the Loss through Auroral Microburst Pulsations (LAMP) sounding rocket that was launched at 11:27:30 UT on 5 March 2022 from Poker Flat Research Range, Alaska. At an altitude of 200–250 km, MIM detected clear enhancements of the magnetic field by 15–25 nT in both the northward and westward components. From simultaneous observations with the ground all‐sky camera, we found that the footprint of LAMP at the 100 km altitude was located near the center of a pulsating auroral patch. The auroral patch had a dimension of ∼90 km in latitude and ∼25 km in longitude, and its major axis was inclined toward northwest. These observations were compared with results of a simple model calculation, in which local electron precipitation into the thin‐layer ionosphere causes an elliptical auroral patch. The conductivity within the patch is enhanced in the background electric field and as a result, the magnetic field variations are induced around the auroral patch. The model calculation results can explain the MIM observations if the electric field points toward southeast and one of the model parameters is adjusted. We conclude that the pulsating auroral patch in this event was associated with a one‐pair field‐aligned current that consists of downward (upward) currents at the poleward (equatorward) edge of the patch. This current structure is maintained even if the auroral patch is latitudinally elongated. Magneto‐impedance (MI) sensor was carried by a sounding rocket and first applied to magnetic field measurement in spaceMagnetic field variations were observed when the footprint of the payload was located near the center of an auroral patchThe magnetic field variations are thought to be caused by field‐aligned currents flowing at the edges of the pulsating auroral patch Magneto‐impedance (MI) sensor was carried by a sounding rocket and first applied to magnetic field measurement in space Magnetic field variations were observed when the footprint of the payload was located near the center of an auroral patch The magnetic field variations are thought to be caused by field‐aligned currents flowing at the edges of the pulsating auroral patch

Cell sorting is important in many studies, from basic science, such as cell biology, to biomedical applications, such as cell engineering and regenerative medicine. We have developed a photoinduced in situ cell detachment system using gold nanoparticle (AuNP)-embedded collagen hydrogels as a spatiotemporal cell sorting system, which is an image-guided cell sorting system. Here, we prepared AuNP-containing collagen coatings as a photosensitive cell scaffold. Various cells cultured on the coating materials were detached by photoirradiation and subsequent medium injection. The monolayer type of AuNP/collagen coatings showed efficient cell detachment with cell damage and may be applied to remove undesired cells. For cell damage suppression, the bilayer-type AuNP/collagen coatings were designed and prepared. We demonstrated the sorting of visually changed transfected CHO-K1 cells and human-induced pluripotent stem cell-derived cardiomyocytes using our system, which is useful for genome editing and regenerative medicine, respectively.

The magneto‐impedance (MI) effect was discovered about 30 years ago and a microsize magnetic sensor utilizing this effect has become commercially available. We make some modifications to the commercially available MI sensors to cover the dynamic range of the geomagnetic field. The total cost of three MI sensors for the two horizontal components and one vertical component including the modification is approximately one‐third of the standard price of triaxial fluxgate magnetometer sensors. For the period of 30 March to 27 April 2018, we conducted experimental observations of geomagnetic field variations with the MI sensor magnetometer (MIM) at the Mineyama observatory, which is located about 100 km northwest of Kyoto, Japan. Data obtained with the MIM are compared with those from the fluxgate magnetometer (FGM) that has been working at the observatory. Results show that the MIM can record geomagnetic field variations such as geomagnetic storm, solar quiet variations, low‐latitude positive bays, storm sudden commencement, and long‐period geomagnetic pulsations with a peak‐to‐peak amplitude of ≤1 nT that is also detected with the FGM. Power spectra of the geomagnetic field variations measured with the MIM and FGM are almost the same. It is found that the MIM has a larger temperature drift than the FGM. The present study reveals that the MIM is comparable to the FGM in measuring the geomagnetic field variations in a period from a few tens of seconds to a few hours and is useful for researches in upper atmospheric physics or space physics. Magneto‐impedance (MI) sensor is applied for the first time to geomagnetic field measurement at the low‐latitude Mineyama observatoryMI sensor magnetometer (MIM) can record magnetic storm, storm sudden commencement, solar quiet, low‐latitude positive bay, and long period geomagnetic pulsationsMIM is compared to fluxgate magnetometer in measuring geomagnetic field variations with periods from 10s of seconds to a few hours Magneto‐impedance (MI) sensor is applied for the first time to geomagnetic field measurement at the low‐latitude Mineyama observatory MI sensor magnetometer (MIM) can record magnetic storm, storm sudden commencement, solar quiet, low‐latitude positive bay, and long period geomagnetic pulsations MIM is compared to fluxgate magnetometer in measuring geomagnetic field variations with periods from 10s of seconds to a few hours

Chronic myelogenous leukemia (CML) is caused by expression of the Bcr-Abl fusion protein in hematopoietic stem cells. The MUC1-C oncoprotein is expressed in CML blasts and stabilizes Bcr-Abl. The present studies demonstrate that treatment of KU812 and K562 CML cells with GO-201, a cell-penetrating peptide inhibitor of MUC1-C oligomerization, downregulates Bcr-Abl expression and inhibits cell growth. In concert with decreases in Bcr-Abl levels, KU812 and K562 cells responded to GO-201 with induction of a differentiated myeloid phenotype as evidenced by increased expression of CD11b, CD11c and CD14. The results also show that the GO-201-treated cells undergo a late apoptotic/necrotic response, consistent with induction of terminal differentiation. Primary CML blasts expressing MUC1 similarly responded to GO-201 with induction of a more differentiated phenotype and late apoptosis/necrosis. In addition, treatment of KU812 xenografts in nude mice was associated with upregulation of CD11 and tumor regression. These findings indicate that CML blasts respond to targeting of the MUC1-C oncoprotein with induction of terminal differentiation.

Tyrosinase (monophenol, 3,4-dihydroxy L-phenylalanine (L-DOPA):oxygen oxidoreductase, EC 1.14.18.1) was isolated from fruit bodies of Pholiota namekoand purified to homogeneity. The purified enzyme was a monomer with a molecular weight of 42,000 and contained 1.9 copper atoms per molecule. The N-terminal of the purified enzyme could not be detected by Edman degradation, probably due to blocking, while the C-terminal sequence of the enzyme was determined to be -Ala-Ser-Val-Phe-OH. The amino acid sequence deduced by cDNA cloning was made up of 625 amino acid residues and contained two putative copper-binding sites highly conserved in tyrosinases from various organisms. The C-terminal sequence of the purified enzyme did not correspond to that of the deduced sequence, but agreed with Ala384-Ser385-Val386-Phe387 in sequence. When the encoded protein was truncated at Phe387, the molecular weight of the residual protein was calculated to be approximately 42,000. These results suggest that P. namekotyrosinase is expressed as a proenzyme followed by specific cleavage to produce a mature enzyme.

An updated batch-to-batch difference table of IAPSO standard seawater (SSW) up to P145 is proposed. The batch-to-batch difference table is based on several recent SSW comparison experiments, including the experiments conducted independently at the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) and Woods Hole Institute of Oceanography (WHOI) at about the same time using the same procedure. Proposed batch-to-batch differences range from 1.2 × 10−3to −1.9 × 10−3with reference to the average of those from P91 to P102. Batch-to-batch differences from P29 to P145 with reference to the recent batches and this average over every 5 years since 1960 are also presented, together with standard deviation. This reveals that inconsistency among batches has improved since 1980s. In particular, the standard deviation was 0.3 × 10−3in this decade, which is about one-half the value reported previously and almost equal to the modern measurement precision (0.2 × 10−3) and is within-batch difference (<0.3 × 10−3). Proposed batch-to-batch differences were applied to the observational results of the WOCE hydrographic onetime section (WHP onetime) in the Indian Ocean. Average absolute salinity differences at 14 crossover points in the Indian Ocean were slightly larger, from 1.2 × 10−3to 1.5 × 10−3, when the batch-to-batch difference table was applied; however, when results from the Indian, Pacific, and Atlantic Oceans were combined, application of the batch-to-batch difference table yielded statistically acceptable salinity differences. The table was also applied to WHP sections P1 and P17 (revisited about 10 years after the original observations during the WOCE period) and sections I1, I7, and I8 (visited twice by different research vessels in the same year). In all cases, the table corrected unrealistically large salinity changes in space and time. The results suggest that the application of the batch-to-batch table to well-controlled salinity data such as WOCE datasets would be effective in making the datasets more consistent in space and time.

K562 cells contain a Bcr-Abl chimeric gene and differentiate into various lineages in response to different inducers. We studied the role of the mitogen-activated protein kinase (MAPK) kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK) pathway during the erythroid differentiation of K562 cells induced by tyrosine kinase inhibitors (herbimycin A or STI571), using genetically modified cells (constitutively MEK1-activated K562: K562/MEK1, and inducible ERK-inactivated K562: K562/CL100). Basal expression of glycophorin A was markedly reduced in K562/MEK1 cells compared with that in parental cells, while it was augmented in K562/CL100 cells. Herbimycin A and STI571 differentiated K562 cells accompanying with the transient down-regulated ERK. Moreover, the erythroid differentiation was markedly suppressed in K562/MEK1 cells, and early down-regulation of ERK activity was not observed in these cells. In contrast, the induction of ERK-specific phosphatase in K562/CL100 cells potentiated erythroid differentiation. Once the phosphatase was induced, the initial ERK activity became repressed and its early down-regulation by the inhibition of Bcr-Abl was marked and prolonged. These results demonstrate that the erythroid differentiation of K562 cells induced by herbimycin A or STI571 requires the down-regulation of MEK1/ERK pathway.

Therapeutic strategies for leukemia are directed to induction of differentiation and apoptosis as well as growth inhibition. One of the key antileukemic agents, 1-β-D-arabinofuranosylcytosine (ara C), is clinically applied according to these therapeutic aims. However, the molecular effects of 0.1 μg/ml of ara C, a concentration that corresponds to the serum level in leukemic patients on a conventional dose of ara C, have not been well disclosed. Here, we addressed these issues using K562 cells which derived from a blastic crisis of chronic myeloid leukemia. DNA synthesis of treated cells was suppressed from 1-6 h. But, it recovered at 12 h and no further inhibition was observed. The number of cells was not decreased but DNA fragmentation was observed at 72 h. The number of erythroid-differentiated cells also increased to 30% at 72 h. Along with treatment, no marked alteration of mRNAs for cell cycle-regulating genes was found and the retinoblastoma gene product remained hyperphosphorylated throughout treatment. The expression of mRNAs for apoptosis-regulating genes also remained unchanged, except for slight down-regulation of Bax. c-myc protein was not found later than 48 h, and Max mRNA was downregulated. c-jun was immediately induced, followed by the fluctuated expression level along with treatment. These findings suggest that the 0.1 μg/ml ara C changed the proliferation, differentiation and death of K562 cells in a biphasic manner. In the early phase, DNA synthesis was inhibited without altering the expression of cell cycle regulating-genes. In the latter phase, cell death and erythroid- differentiation occurred in accordance with the down-regulation of c-myc.

Stretchable electronics are significantly used to integrate electronic devices with soft biological tissues. However, conventional stretchable devices have limited applications because of their higher Young's modulus and instability in wet environments. In article number 1900939, Takeshi Kawano and co‐workers propose a donut‐shaped‐kirigami device that can envelop the muscle, allowing the device to stretch and follow muscle deformation and robust EMG signal recordings.

Electronic devices used to record biological signals are important in neuroscience, brain–machine interfaces, and medical applications. Placing electronic devices below the skin surface and recording the muscle offers accurate and robust electromyography (EMG) recordings. The device stretchability and flexibility must be similar to the tissues to achieve an intimate integration of the electronic device with the biological tissues. However, conventional elastomer‐based EMG electrodes have a Young's modulus that is ≈20 times higher than that of muscle. In addition, these stretchable devices also have an issue of displacement on the tissue surface, thereby causing some challenges during accurate and robust EMG signal recordings. In general, devices with kirigami design solve the issue of the high Young's modulus of conventional EMG devices. In this study, donut‐shaped kirigami bioprobes are proposed to reduce the device displacement on the muscle surface. The fabricated devices are tested on an expanding balloon and they show no significant device (microelectrode) displacement. As the package, the fabricated device is embedded in a dissolvable material‐based scaffold for easy‐to‐use stretchable kirigami device in an animal experiment. Finally, the EMG signal recording capability and stability using the fabricated kirigami device is confirmed in in vivo experiments without significant device displacements. Stretchable electronics are significantly used to integrate electronic devices with soft biological tissues. However, conventional stretchable devices have limited applications because of the higher Young's modulus and instability in wet environments. In this study, a proposed donut‐shaped‐kirigami device envelopes the muscle, which is unaffected by the muscle deformation and thus achieves robust electromyography signal recordings.

Microelectrode devices, which enable the detection of neuronal signals in brain tissues, have made significant contributions in the field of neuroscience and the brain–machine interfaces. To further develop such microelectrode devices, the following requirements must be met: i) a fine needle's diameter (<30 µm) to reduce damage to tissues; ii) a long needle (e.g., ≈1 mm for rodents and ≈2 mm for macaques); and iii) multiple electrodes to achieve high spatial recording (<100 µm in pitch). In order to meet these requirements, this study herein reports an assembly technique for high‐aspect‐ratio microneedles, which employs a magnet. The assembly is demonstrated, in which nickel wires of length 750 µm and diameter 25 µm are produced on a silicon substrate. The impedance magnitude of the assembled needle‐like electrode measured at 1 kHz is 5.6 kΩ, exhibiting output and input signal amplitudes of 96.7% at 1 kHz. To confirm the recording capability of the fabricated device, neuronal signal recordings are performed using mouse cerebra in vivo. The packaged single microneedle electrode penetrates the barrel field in the primary somatosensory cortex of the mouse and enables the detection of evoked neuronal activity of both local field potentials and action potentials. Microelectrodes have made significant contributions in neuroscience.However, further improvements (e.g., fine diameter, long needle, and high‐density arrays) are required. To achieve such requirements, a microneedle assembly technique using a magnet is reported. The assembly of the nickel wires and in vivo neuronal recording capability of the fabricated microelectrode using mouse cerebra are demonstrated.

The most remarkable features of Kirigami are that unstretchable materials can gain stretchability and that its strain force is very small compared to other elastomer‐based stretchable materials. These features are suitable for applications related to deformable soft biological samples. In article number 1701100, Takeshi Kawano and co‐workers propose the ultrastretchable bioprobe device using a ‘Kirigami’ design and demonstrate the recordings of biological signals in mouse brain and heart.

An ultrastretchable film device is developed that can follow the shape of spherical and large deformable biological samples such as heart and brain tissues. Although the film is composed of biocompatible parylene for the device substrate and metal layers of platinum (Pt)/titanium (Ti), which are unstretchable materials, the film shows a high stretchability by patterning slits as a “Kirigami” design. A Pt/Ti‐microelectrode array embedded in 11 µm thick parylene film with 5 × 91 slits exhibits a film strain of ≈250% at 9 mN strain‐force (0.08 MPa in stress) with a Young's modulus of 23 kPa, while the 3 × 91‐slit film shows a Young's modulus of 3.6 kPa. The maximum strains of these devices are ≈470% and ≈840%, respectively. It is demonstrated that the Kirigami‐based microelectrode device can simultaneously record in vivo electrocorticogram signals from the visual and barrel cortices of a mouse by stretching the film and tuning the electrode gap. Moreover, wrapping the Kirigami device around a beating mouse's heart, which shows large and rapid changes in the volume and the surface area, can record the in vivo epicardial electrocardiogram signals. Such a small Young's modulus for a stretchable device reduces the device's strain‐force, minimizing the device‐induced stress to soft biological tissues. High‐stretchability and high‐deformability are promising properties to expand the applications of flexible devices, including sensors, actuators, and energy harvesters. However, the stretchability of conventional devices is limited by the elasticity of the material's interconnections. In this study, the device limitations are overcome utilizing a concept from the Japanese culture known as “Kirigami.”

A self-supporting thin film is useful as a target material for laser-driven ion acceleration experiments. In this study, 100-nm-thick sputtered gold (Au) thin films were released from substrates using water-soluble sacrificial layers, and the released films were subsequently scooped up on perforated substrates. Au thin films were deposited by DC plasma sputtering on the sacrificial layers. In the releasing test, sodium chloride (NaCl) was shown to be most suitable as a sacrificial layer for Au thin films. In addition, sputtered Au thin films with thicknesses of 50 and 150 nm were deposited onto NaCl sacrificial layers, released on water, and scooped up on perforated substrates. Self-supporting Au thin films were obtained for all film thicknesses, but wrinkles and cracks appeared in the 50 nm film.

An inflammatory response of epithelial cells may be co-opted to promote cancer cell survival.

Megakaryocytes and erythroblasts differentiate from MEPs, but the mechanism of lineage shift of MEPs to either megakaryocyte or erythroblast still remains unknown. Transcription factors, GATA DNA-binding genes, ETS family genes, EKLF and RUNX1, play a key role in megakaryocytic and erythroid differentiation. Among them, FLI1, one of ETS family, is considered to play the main role for determination of megakaryocytic differentiation. We previously reported a unique leukemia cell line, JAS-R, being a good model to study the megakaryo-erythroid divergence mechanisms (Leukemia Res. 2007 G 31:1537-43). These cells acquire megakaryocytic phenotypes by adhesion to extracellular matrices. We examined how cell attachment augments FLI1 expression.JAS-R cells, a megakaryo-erythroid cell line, were used. Gene transfection was done by electroporation. FLI1 promoter activity was measured by luciferase reporter gene assay. Knock-down of a specific gene function was obtained by RNA-interference using a short-hairpin expression vector. Messenger RNAs were studied by Northern blot or RT-PCR. Protein was studied by Immunoblot. Integrins were analyzed by flow cytometry.As previously reported, JAS-R cells were segregated into two populations depending on adhesion. One is adherent megakaryocytic cells (JAS-RAD), and the other is floating erythroid cells (JAS-REN). JAS-RAD expressed higher amount of FLI1 message. Knock-down of FLI1 gene by short-hairpin RNA (shFLI1) reduced the adhesion (80% of JAS-RAD cells transfected with control vector adhered compared to 45% of shFLI1-transfected). Changes of CD41 and CD61 were studied by flow cytometry. The mean fluorescence of both CD41 and CD61 was significantly decreased in FLI1 knock-downed cells. While FLI1 was high in JAS-RAD cells, the expression of NFE2 did not differ. Thus, transcriptional activity of two genes was examined in JAS-RAD and JAS-REN cells. Luciferase reporter gene experiments revealed that the promoter activity of FLI1 gene (-835 to -36 from translation initiation site) was dramatically high in JAS-RAD, while the NFE2 promoter was equal in both lineages. These data demonstrated that the adhesion increases the FLI1 promoter activity in JAS-RAD cells, leading megakaryocytic differentiation. Next, we searched the region of FLI1 promoter responsive for the activation in JAS-RAD. A series of deletion vectors disclosed that -596 to -417 contained the critical region responsible for the difference between JAS-RAD and JAS-REN cells. Luciferase assay carried out with mutations in each transcription factor binding site demonstrated that GATA- and ETS-binding sites were responsible for the transcription in JAS-RAD, but NFkB, AP1, or STAT binding sites were not. Indeed, the FLI1 promoter activity decreased to the half by introduction of shFLI1 indicates the existence of auto-augmentation mechanisms of FLI1 gene. Next, we studied whether the interference of adhesion affected on the FLI1 promoter activity. JAS-RAD cells did not attach on the substratum of Ultra Low Attachment surface culture dishes, instead they aggregated and grew as floating cells. The promoter activity decreased by 20% in Ultra Low dishes, and this reduction was significant. Knock-down of either ITGB1 or ITGB3 gene by shRNA failed to reduce the FLI1 promoter activity, but the concomitant knock-down of two integrin genes reduced the promoter activity by 50%.Several lines of evidences support the important function of cell adhesion for maintenance and differentiation of hematopoietic cells. Our data support that once cell-attachment occurs in JAS-R cells, FLI1 is induced, and adhesion molecules increase profoundly. Adherent cells further augment FLI1 itself and are critically destined to differentiate into megakaryocytes.No relevant conflicts of interest to declare.

Abstract 3650