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Abstract Subducting oceanic plates carry large amounts of carbon into the Earth’s interior. The subducted carbon is mobilized by fluid and encounters ultramafic rocks in the mantle wedge, resulting in changes to the mineral assemblage and mechanical properties of the mantle. Here, we use thermodynamic modeling of interactions between carbon-bearing multi-component fluids and mantle rocks to investigate the down-dip variation in mineral assemblage in the forearc mantle along subduction megathrusts. We found that fluids rich in aqueous carbon are preferentially generated in a warm subduction zone (e.g., Nankai, SW Japan), causing a change in mineral assemblage from serpentine-rich at the mantle wedge corner to talc + carbonate-rich at greater depths. The transition caused by the infiltration of aqueous carbon may influence the depth of the boundary between the seismogenic and aseismic zones, and the down-dip limit of episodic tremor and slip.

Abstract Breccia and pulverized rock are typical textures in off-fault damage adjacent to a main seismogenic zone. Previously, by estimating the energy required to advance the rupture in this zone using particle size distribution at sub-millimeter/micrometer scales, we could constrain the energy budget during coseismic events. However, whether microscopic estimation is sufficient to capture surface energy fragmentation during an earthquake and the effect of measurement scale variation on calculation of co-seismic energy partitioning remained unclear. Here, we investigated the mechanism of coseismic off-fault damage based on field and microstructural observations of a well-exposed breccia body in Ichinokawa, Japan. We used in situ clast measurements coupled with thin-section analysis of breccia clasts to estimate the energy budget of the damage zone adjacent to the principal slip zone of the Median Tectonic Line (MTL). The total surface energy density and corresponding surface energy per unit fault for a width of ~ 500 m of the dynamical damage zone were estimated. The moment magnitude estimated based on surface energy was 5.8–8.3 Mw. In Ichinokawa, off-fault fragmentation is initiated by coseismic activity and is followed by fluid activity. Under dynamic fragmentation conditions, the scale is important to calculate the surface energy.

Abstract A 76‐year‐old woman with cT1bN2M1b stage IVA spindle cell carcinoma of the right lower lobe of the lung, no driver gene mutation, and programmed death ligand 1

Abstract The slab–mantle interface in subduction zones is one of the geological boundaries with the most significant chemical potential gradients, which leads to fluid-mediated metasomatic reactions and chemical transport. As subducting sediment and basaltic crust often contain silica in various forms, the Si-metasomatism of mantle rocks is thought to occur along the subduction zone interface. However, growing evidence from the geochemistry of altered rocks and thermodynamic modelling has revealed the presence of multi-component fluids at the slab interface. Here, we review the laboratory experiments, geochemical models, and natural observations that improve our understanding of mass transport and metasomatic reactions at the crust–mantle interface, focusing on the relative mobility of Mg and Si. Hydrothermal experiments using analogues for the boundary between mantle (olivine) and crust (quartz or plagioclase) under vapor-saturated pressures indicate that Si is preferentially transported from crust to mantle, whereas Mg is immobile. This result is consistent with the distribution of talc rocks in oceanic lithosphere. On the other hand, at the contact between ultramafic (e.g., serpentinite) and crustal (pelitic schist or basaltic rocks) rocks in high-pressure metamorphic terranes, a large volume of chlorite rocks form in the crustal rocks, and the volume of chlorite often exceeds talc in serpentinites. Geochemical modeling reveals that in the shallow part of a subduction zone, the dissolved Si content of fluids in equilibrium with pelitic schist (C Si,crust) is significantly higher than the dissolved Mg content of fluids in equilibrium with mantle peridotite (C Mg,mantle); however, C Mg,mantle becomes dominant at depth, resulting in the Mg-metasomatism of crustal rocks to form chlorite rocks. This Mg-metasomatism is more widespread in warmer subduction zones (e.g., the Nankai and Cascadia subduction zones) than in colder subduction zones (e.g., in Northeast Japan). In addition, the infiltration of CO2-bearing fluid can form talc (along with carbonates) in ultramafic rocks without Si-metasomatism. Variations in the relative mobility of Si and Mg at the subduction zone interface produce variations in the overall solid volume change of mantle (expansion or contraction), the types of sheet silicates (talc versus chlorite), and the fluid budget (dehydration or hydration) during metasomatic reactions, which affects the pore fluid pressure, frictional strength of the subduction megathrust, and the location of seismicity around the mantle wedge corner.

Abstract Nanometer-sized crystals (nanolites) play an important role in controlling eruptions by affecting the viscosity of magmas and inducing bubble nucleation. We present detailed microscopic and nanoscopic petrographic analyses of nanolite-bearing and nanolite-free pumice from the 2021 eruption of Fukutoku-Oka-no-Ba, Japan. The nanolite mineral assemblage includes biotite, which is absent from the phenocryst mineral assemblage, and magnetite and clinopyroxene, which are observed as phenocrysts. The boundary between the nanolite-bearing brown glass and nanolite-free colorless glass is either sharp or gradational, and the sharp boundaries also appear sharp under the transmitted electron microscope. X-ray absorption fine structure (XAFS) analysis of the volcanic glass revealed that the nanolite-free colorless glass records an oxygen fugacity of QFM + 0.98 (log units), whereas the nanolite-bearing brown glass records a higher apparent oxygen fugacity (~ QFM + 2). Thermodynamic modelling using MELTS indicates that higher oxygen fugacities increase the liquidus temperature and thus induced the crystallization of magnetite nanolites. The hydrous nanolite mineral assemblage and glass oxygen fugacity estimates suggest that an oxidizing fluid supplied by a hot mafic magma induced nanolite crystallization in the magma reservoir, before the magma fragmentation. The oxidation-induced nanolite crystallization then enhanced heterogeneous bubble nucleation, resulting in convection in the magma reservoir and triggering the eruption.

Abstract X-ray computed tomography (X-ray CT) has been widely used in the earth sciences, as it is non-destructive method for providing us the three-dimensional structures of rocks and sediments. Rock samples essentially possess various-scale structures, including millimeters to centimeter scales of layering and veins to micron-meter-scale mineral grains and porosities. As the limitations of the X-ray CT scanner, sample size and scanning time, it is not easy to extract information on multi-scale structures, even when hundreds meter scale core samples were obtained during drilling projects. As the first step to overcome such barriers on scale-resolution problems, we applied the super-resolution technique by sparse representation and dictionary-learning to X-ray CT images of rock core sample. By applications to serpentinized peridotite, which records the multi-stage water–rock interactions, we reveal that both grain-shapes, veins and background heterogeneities of high-resolution images can be reconstructed through super-resolution. We also show that the potential effectiveness of sparse super-resolution for feature extraction of complicated rock textures.

Measurement-device-independent quantum key distribution (MDI-QKD) protects legitimate users from attacks on measurement devices. The decoy method allows for unconditionally secure quantum key generation using lasers. One of the most important issues in MDI-QKD is that photons from two independent lasers must be indistinguishable. Because Alice and Bob send Charlie laser pulses through separate fiber links, the arrival times of the pulses fluctuate independently. According to the Hong-Ou-Mandel (HOM) interference at Charlie's relay, the time delay between two photons has the greatest effect on distinguishability. However, to date, these effects have not been analyzed. Our study uses simulations to investigate the effects of two-photon temporal distinguishability in terms of the visibility of the HOM-dip of two photons on the final key rate of finite-size MDI-QKD. Furthermore, an acceptable time delay range was estimated based on photons with Gaussian spectral amplitude functions.

Abstract The mass transfer history of rocks provides direct evidence for fluid–rock interaction within the lithosphere and is recorded by compositional changes, especially in trace elements. The general method adopted for mass transfer analysis is to compare the composition of the protolith/precursor with that of metamorphosed/altered rocks; however, in many cases the protolith cannot be sampled. With the aim of reconstructing the mass transfer history of metabasalt, this study developed protolith reconstruction models (PRMs) for metabasalt using machine-learning algorithms. We designed models to estimate basalt trace-element concentrations from the concentrations of a few (1–9) trace elements, trained with a compositional dataset for fresh basalts, including mid-ocean ridge, ocean-island, and volcanic arc basalts. The developed PRMs were able to estimate basalt trace-element compositions (e.g., Rb, Ba, U, K, Pb, Sr, and rare-earth elements) from only four input elements with a reproducibility of ~ 0.1 log10 units (i.e., ± 25%). As a representative example, we present PRMs where the input elements are Th, Nb, Zr, and Ti, which are typically immobile during metamorphism. Case studies demonstrate the applicability of PRMs to seafloor altered basalt and metabasalt. This method enables us to analyze quantitative mass transfer in regional metamorphic rocks or alteration zones where the protolith is heterogeneous or unknown.

Differentiating the intrinsic subtypes of breast cancer is crucial for deciding the best treatment strategy. Deep learning can predict the subtypes from genetic information more accurately than conventional statistical methods, but to date, deep learning has not been directly utilized to examine which genes are associated with which subtypes. To clarify the mechanisms embedded in the intrinsic subtypes, we developed an explainable deep learning model called a point-wise linear (PWL) model that generates a custom-made logistic regression for each patient. Logistic regression, which is familiar to both physicians and medical informatics researchers, allows us to analyze the importance of the feature variables, and the PWL model harnesses these practical abilities of logistic regression. In this study, we show that analyzing breast cancer subtypes is clinically beneficial for patients and one of the best ways to validate the capability of the PWL model. First, we trained the PWL model with RNA-seq data to predict PAM50 intrinsic subtypes and applied it to the 41/50 genes of PAM50 through the subtype prediction task. Second, we developed a deep enrichment analysis method to reveal the relationships between the PAM50 subtypes and the copy numbers of breast cancer. Our findings showed that the PWL model utilized genes relevant to the cell cycle-related pathways. These preliminary successes in breast cancer subtype analysis demonstrate the potential of our analysis strategy to clarify the mechanisms underlying breast cancer and improve overall clinical outcomes.

Veins of aragonite in deep ocean trenches can record discharges of CO2-rich paleoseawater and suggest that exposed serpentinized forearcs can act as carbon reservoirs, according to residence time calculations based on geochemical analyses of mantle rocks from offshore Japan.

Serpentinization of ultramafic rocks in ophiolites is key to understanding the global cycle of elements and changes in the physical properties of lithospheric mantle. Mongolia, a central part of the Central Asian Orogenic Belt (CAOB), contains numerous ophiolite complexes, but the metamorphism of ultramafic rocks in these ophiolites has been little studied. Here we present the results of our study of the serpentinization of an ultramafic body in the Manlay Ophiolite, southern Mongolia. The ultramafic rocks were completely serpentinized, and no relics of olivine or orthopyroxene were found. The composition of Cr-spinels [Mg# = Mg/(Mg + Fe2+) = 0.54 and Cr# = Cr/(Cr + Al) = 0.56] and the bulk rock chemistry (Mg/Si = 1.21–1.24 and Al/Si < 0.018) of the serpentinites indicate their origin from a fore-arc setting. Lizardite occurs in the cores and rims of mesh texture (Mg# = 0.97) and chrysotile is found in various occurrences, including in bastite (Mg# = 0.95), mesh cores (Mg# = 0.92), mesh rims (Mg# = 0.96), and later-stage large veins (Mg# = 0.94). The presence of lizardite and chrysotile and the absence of antigorite suggests low-temperature serpentinization (

Carbonation of a serpentinized mantle wedge is associated with volume reduction and fluid over-pressurization which drives brittle fracture and seismicity, according to chemical analyses of carbonate veins from the Sanbagawa belt Japan and thermodynamic calculations.

Abstract Destructive landslides were triggered by the 6.7 M w Eastern Iburi earthquake that struck southern Hokkaido, Japan, on 6 September 2018. In this study, we carried out 1-D inversion analysis of one of the shallow landslides near the epicenter using a Bing debris-flow model. At this site, the slope failure comprised cover soil with an initial down-slope length of ~ 80 m and a thickness of ~ 7 m on a slope with

Abstract Superhot geothermal environments in granitic crusts of approximately 400–500 °C are a frontier of geothermal energy. In the development of such environments, there is a concern of a reduction of permeability of fractured granite due to the formation of fine particles of amorphous silica induced by the phase change from subcritical water to supercritical water or superheated steam. However, the formation of silica particles and a resultant reduction in permeability have not been demonstrated to date. Therefore, experiments were conducted on the formation of amorphous silica particles with various combinations of temperature (430–500 °C) and pressure (20–30 MPa), in which the phase change of Si-containing water from liquid to either supercritical fluid or vapor was induced. Amorphous silica nanoparticles occurred under all conditions with smaller particles for higher temperature. The permeability of fractured granite was also observed to decrease significantly within several hours during injection of the particles into rock at 450 °C and 30 MPa under a confining stress of 40 MPa, with slower permeability reduction at a smaller number of particles or in the presence of larger aperture fractures. The present study suggests that the nanoparticles are likely to form and destroy the permeability in superhot geothermal environments, against which countermeasures should be investigated.

The ion temperature of the smallest tokamak, the major radius of 0.1 m, is measured using Doppler broadening spectroscopy. Experiments are performed for helium discharge. Ion temperature Ti = 0.7eV is obtained from the Doppler broadened line spectrum of the helium ion. The electron temperature and density measured using line emission intensities of the helium atom are Te = 4.7eV and ne = 3.2 × 1018m−3. The major radius R0 = 0.11m and the minor radius a = 0.03m are obtained from magnetic measurements. Then, the energy flow from the electron to the ion is evaluated as well as ohmic heating and power losses due to atomic processes. The main loss channel for electron stored energy is conduction even though the tokamak is immersed in the residual neutral gas. Total energy confinement time τE = 2.3µs is determined from the power balance, which is comparable with that deduced from the neo-Alcator scaling law.

Abstract Background The anesthetic management of cesarean sections in Fontan-palliated parturients requires strict hemodynamic control. However, patient management with central venous oxygen saturation (ScvO2) and oxygen consumption (VO2) has never been reported. Case presentation A 30-year-old woman, who had received a total cavopulmonary connection for tricuspid atresia, was planned to undergo cesarean section at 38 weeks’ gestation. During combined spinal-epidural anesthesia, ScvO2 in addition to arterial pressure-based cardiac output (APCO) and central venous pressure (CVP) was monitored, and the change of VO2 was evaluated. After delivery, her APCO was almost unchanged. However, her ScvO2 increased dramatically from 42.1 to 67.3% and her CVP increased from 9 to 11 mm Hg. The calculated mean maternal VO2 changed from 443 to 295 mL/min. Conclusions In a cesarean section for a Fontan-palliated parturient, ScvO2 dramatically increased and maternal VO2 decreased by more than 25% after delivery.

We investigated the fluid flow and elemental transport from a granitic body to the middle crust by determining the trace element compositions of garnet in pegmatites related to a quartz diorite intrusion and metamorphic rocks on Kinkasan Island, northeast Japan. Garnet in the pegmatites and biotite schists is characterized by spessartine– (Sps–) almandine- (Alm-) rich compositions of Sps14–69Alm22–70Prp2–14Grs1–13 and Sps16–30Alm54–66Prp9–16Grs3–6, respectively. A garnetite pod in the metamorphic unit has grossular- (Grs-) rich compositions (Sps1–4Alm8–11Prp0.1–0.4Grs80–87Adr3–4). The peak temperature (T) and pressure (P) conditions of the biotite schist during contact metamorphism were 600–650°C and 0.27–0.41 GPa, respectively. The primary fluid inclusions in quartz crystals within the pegmatites hosted by the quartz diorite and hosted by the metamorphic rocks have a wide range of homogenization temperatures (200–380°C). These correspond to the trapping temperature of 500–700°C, assuming a salinity of 4 wt.% NaClequivalent at pressure of the crystallization of the quartz diorite. Chondrite-normalized rare earth element (REE) patterns of garnets in the pegmatites in the quartz diorite and metamorphic unit are generally characterized by enrichment of heavy REEs and negative Eu anomalies with the REE contents in the schists which are systematically lower than in the pegmatites. However, garnet in the biotite schists close to the pegmatites has similar REE contents to garnet in the adjacent pegmatites. These geochemical features suggest that garnet in the biotite schists grew in response to fluid infiltration from the pegmatites. Besides, the Grs-rich garnet in the garnetite pod and its host quartz schist have flat heavy REE patterns and no Eu anomalies, which probably reflect a metasomatic process related to plagioclase replacement that produced Ca-Al-rich fluids. Our results suggest that the infiltration of pegmatitic fluids enhances elemental transport and metamorphic reactions in the middle crust.

A retarding field analyzer (RFA) that consists of three grids and a collector was developed, and the measurement of an ion beam that passes through plasma was demonstrated. First, a suitable grid potential structure to allow the measurement of an ion beam in plasma was investigated. After this investigation, a helium ion beam was measured without the production of plasma. It was found that the helium ion beam current was significantly overestimated when an unoptimized potential structure was utilized. One probable reason for the overestimation is secondary electron emission. Next, ion beam measurement in low density helium ionizing plasma was conducted. Accompanying the onset of the beam extraction, the collector current clearly increased, which implies that the beam ions penetrated through the plasma and reached the RFA. Subsequently, similar measurements were conducted after the electron density of the helium plasma was changed. Since a nearly identical beam extraction condition was retained, the ion beam current obtained after plasma production was almost constant. However, the ion beam current obtained during plasma production increased as the electron density increased. A calculation of the ion beam envelope indicated that space charge neutralization by bulk electrons could account for the increase in the ion beam current.

Unmanned aerial vehicles (UAVs) or drones have revolutionized scientific research in multiple fields. Drones provide us multiple advantages over conventional geological mapping or high-altitude remote sensing methods, in which they allow us to acquire data more rapidly of inaccessible or risky outcrops, and can connect the spatial scale gap in mapping between manual field techniques and airborne, high-altitude remote sensing methods. Despite the decreased cost and technological developments of platforms, sensors and software, the use of drones for geological mapping in Mongolia has not yet been utilized. In this study, we present using of drone in two areas: the Chandman area in which eclogite is exposed and the Naran massif of the Khantaishir ophiolite in the Altai area. Drone yields images with high resolution that is reliable to use and reveals that it is possible to make better formulation of geological mapping. Our suggestion is that (1) Mongolian geoscientists are encouraged to add drones to their geologic toolboxes and (2) drone could open new advance of geological mapping in Mongolia in which geological map will be created in more effective and more detailed way combined with conventional geological survey on ground.

Plate subduction initiation requires weak boundaries between tectonic plates, but how weaknesses develop is unclear. Here, using high-pressure friction experiments on peridotite gouge material, the authors show that hydration reactions contribute to the weak mantle shear zones leading to subduction initiation.

Petrological and fluid inclusion data were used to characterize multiple generations of veins within the Erdenet Cu–Mo deposit, Mongolia, and constrain the evolution of fluids within the magmatic–hydrothermal system. Three types of veins are present (from early to late): quartz–molybdenite, quartz–pyrite, and quartz. The host rock was emplaced at temperatures of 700–750 °C, the first quartz was precipitated from magma-derived supercritical fluids at 650–700 °C, quartz–molybdenite and quartz–pyrite veins were formed at ~600 °C, and the quartz veins were precipitated in response to retrograde silica solubility caused by decreasing temperatures at

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm constituting approximately 15% of newly diagnosed leukemia in adult patients. Development of tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes in patients with chronic CML in chronic phase. However, adverse drug events (ADEs) associated with TKI therapy have influenced drug adherence, resulting in adverse clinical outcomes and a decline in the quality of life (QoL). In this study, we carried out a unique questionnaire survey to evaluate ADEs, which comprised 14 adverse events. We compared drug adherence rates between patients using imatinib and those who switched from imatinib to nilotinib, a second-generation TKI. Following the switch, the total number of ADEs decreased considerably in most cases. Simultaneously, better QoL was observed in the nilotinib group than in the imatinib group. Drug adherence was measured using Morisky’s 9-item Medication Adherence Scale (MMAS). MMAS increased significantly after switching to nilotinib in all cases. Drug adherence is a critical factor for achieving molecular response in patients with CML. In fact, our results showed a strong inverse correlation between clinical outcome (international scale (IS)) and adherence (MMAS), with a stronger tendency in the nilotinib group than in the imatinib group. In conclusion, low occurrence of ADEs induced a high level of QoL and a good clinical response with second-generation TKI nilotinib treatment.

ABSTRACT: In the project activities of the ESCAP/WMO Typhoon Committee (TC), the National institute for Land and Infrastructure Management (NILIM), the SABO (Erosion and Sediment Control) Department of the Ministry of Land, Infrastructure, Transport and Tourism (MLIT), and the SABO and Landslide Technical Center (STC) implemented two projects: ''Sediment-related Disaster Forecasting Warning System Project'' (2002-2008) and ''Project on Hazard Mapping for Sediment-related Disasters'' (2009-2012). The aim of these projects was to distribute Japanese SABO technology, particularly non-structural measures, among TC members. This report presents the concepts and methods related to non-structural measures for sediment-related disaster prevention based on Japanese SABO technology, the contents of the two projects' activities, the preparation of early warning information, the creation of a hazard map, and the preparation of an integrated system for resident evacuation. Keywords: sediment-related disaster prevention, non-structural measures, early warning, hazard map

A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes specific to the mesenteric fat of DR rats and revealed high expression of guanylin and guanylyl cyclase C (GC-C) in some subjects. Our histologic studies revealed that the cellular source of guanylin and GC-C is macrophages. Therefore, we developed double-transgenic (Tg) rats overexpressing guanylin and GC-C in macrophages and found that they were resistant to the effects of HFDs. In the mesenteric fat of HFD-fed Tg rats, Fas and perilipin mRNAs were downregulated, and those of genes involved in fatty acid oxidation were upregulated, compared with the levels in HFD-fed wild-type rats. In vitro studies demonstrated that lipid accumulation was markedly inhibited in adipocytes cocultured with macrophages expressing guanylin and GC-C and that this inhibition was reduced after treatment with guanylin- and GC-C-specific siRNAs. Our results suggest that the macrophagic guanylin-GC-C system contributes to the altered expression of genes involved in lipid metabolism, leading to resistance to obesity.

Background: In Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP. Methods: In this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16–85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph. Results: Initial treatment with FP was significantly (P=0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season. Conclusions: Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.

To implement fault-tolerant quantum computation with continuous variables, the Gottesman-Kitaev-Preskill (GKP) qubit has been recognized as an important technological element. However, it is still challenging to experimentally generate the GKP qubit with the required squeezing level, 14.8 dB, of the existing fault-tolerant quantum computation. To reduce this requirement, we propose a high-threshold fault-tolerant quantum computation with GKP qubits using topologically protected measurement-based quantum computation with the surface code. By harnessing analog information contained in the GKP qubits, we apply analog quantum error correction to the surface code. Furthermore, we develop a method to prevent the squeezing level from decreasing during the construction of the large-scale cluster states for the topologically protected, measurement-based, quantum computation. We numerically show that the required squeezing level can be relaxed to less than 10 dB, which is within the reach of the current experimental technology. Hence, this work can considerably alleviate this experimental requirement and take a step closer to the realization of large-scale quantum computation.

Nucleolar and spindle-associated protein 1 (NUSAP1) is an important mitotic regulator. In addition to its crucial function in mitosis, NUSAP1 has recently received attention due to the interesting roles in carcinogenesis. The aim of this study was to reveal functional mechanisms of NUSAP1 in oral squamous cell carcinoma (OSCC).mRNA and protein expression levels of NUSAP1 in 9 OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analyses. The correlation between the NUSAP1 expression profile and the clinicopathological factors was evaluated by immunohistochemistry (IHC) in clinical OSCC samples (n = 70). The NUSAP1 knockdown cells were established with short hairpin RNA (shRNA) in OSCC cells, and functional assays were performed using these cells. In addition to the evaluation of cellular proliferation and cell cycle, we also investigated the potential role of NUSAP1 in paclitaxel (PTX)-induced cellular responses.mRNA and protein expression of NUSAP1 were significantly up-regulated in OSCC-derived cells compared with human normal oral keratinocytes (P < 0.05). IHC revealed that NUSAP-1 expression is closely associated with primary advanced T stage (P

Micronucleation, mediated by interphase nuclear budding, has been repeatedly suggested, but the process is still enigmatic. In the present study, we confirmed the previous observation that there are lamin B1-negative micronuclei in addition to the positive ones. A large cytoplasmic bleb was found to frequently entrap lamin B1-negative micronuclei, which were connected to the nucleus by a thin chromatin stalk. At the bottom of the stalk, the nuclear lamin B1 structure appeared broken. Chromatin extrusion through lamina breaks has been referred to as herniation or a blister of the nucleus, and has been observed after the expression of viral proteins. A cell line in which extrachromosomal double minutes and lamin B1 protein were simultaneously visualized in different colors in live cells was established. By using these cells, time-lapse microscopy revealed that cytoplasmic membrane blebbing occurred simultaneously with the extrusion of nuclear content, which generated lamin B1-negative micronuclei during interphase. Furthermore, activation of cytoplasmic membrane blebbing by the addition of fresh serum or camptothecin induced nuclear budding within 1 to 10 minutes, which suggested that blebbing might be the cause of the budding. After the induction of blebbing, the frequency of lamin-negative micronuclei increased. The budding was most frequent during S phase and more efficiently entrapped small extrachromosomal chromatin than the large chromosome arm. Based on these results, we suggest a novel mechanism in which cytoplasmic membrane dynamics pulls the chromatin out of the nucleus through the lamina break. Evidence for such a mechanism was obtained in certain cancer cell lines including human COLO 320 and HeLa. The mechanism could significantly perturb the genome and influence cancer cell phenotypes.

The presence of micronuclei in mammalian cells is related to several mutagenetic stresses. In order to understand how micronuclei emerge, behave in cells, and affect cell fate, we performed extensive time-lapse microscopy of HeLa H2B-GFP cells in the presence of hydroxyurea at low concentration. Micronuclei formed after mitosis from lagging chromatids or chromatin bridges between anaphase chromosomes and were stably maintained in the cells for up to one cell cycle. Nuclear buds also formed from chromatin bridges or during interphase. If the micronuclei-bearing cells entered mitosis, they either produced daughter cells without micronuclei or, more frequently, produced cells with additional micronuclei. Low concentrations of hydroxyurea efficiently induced multipolar mitosis, which generated lagging chromatids or chromatin bridges, and also generated multinuclear cells that were tightly linked to apoptosis. We found that the presence of micronuclei is related to apoptosis but not to multipolar mitosis. Furthermore, the structural heterogeneity among micronuclei, with respect to chromatin condensation or the presence of lamin B, derived from the mechanism of micronuclei formation. Our study reinforces the notion that micronucleation has important implications in the genomic plasticity of tumor cells.