Anatase and rutile titanium oxide nanoparticles induce acute kidney injury by coadministration with paraquat, cisplatin or 5-aminosalicylic acid.

Nanoparticles are used in a variety of fields; for example, titanium oxide nanoparticles are used in paints, food additives, cosmetics, and sunscreen materials. Although the use of titanium oxide nanoparticles is regulated, their safety has not been established. Furthermore, the interaction between titanium oxide nanoparticles and various chemical substances and pharmaceuticals is unknown. We co-administered rutile-type titanium oxide nanoparticles (nTR) or anatase-type titanium oxide nanoparticles (nTA) to mice together with paraquat (PQ), cisplatin (CDDP), or anti-5-aminosalicylic acid (5-ASA), and investigated the extent, if any, of liver and kidney injury. As a result, when nTA and nTR were administered alone, no increases were observed in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are indicators of liver damage, or urea nitrogen (BUN), which is an indicator of kidney damage. Next, nTA and nTR were co-administered with PQ, CDDP or 5-ASA. Although no increase in ALT or AST was observed, BUN levels increased significantly and acute kidney injury was induced. The findings suggested that titanium oxide nanoparticles induce acute kidney injury through their interaction with chemicals and drugs.

Lossless Positron Injection into a Magnetic Dipole Trap.

The high-efficiency injection of a low-energy positron beam into the confinement volume of a magnetic dipole has been demonstrated experimentally. This was accomplished by tailoring the three-dimensional guiding-center drift orbits of positrons via optimization of electrostatic potentials applied to electrodes at the edge of the trap, thereby producing localized and essentially lossless cross-field particle transport by means of the E×B drift. The experimental findings are reproduced and elucidated by numerical simulations, enabling a comprehensive understanding of the process. These results answer key questions and establish methods for use in upcoming experiments to create an electron-positron plasma in a levitated dipole device.

Confinement of Positrons Exceeding 1 s in a Supported Magnetic Dipole Trap.

An ensemble of low-energy positrons injected into a supported magnetic dipole trap can remain trapped for more than a second. Trapping experiments with and without a positive magnet bias yield confinement times up to τ_{A}=(1.5±0.1) and τ_{B}=(0.28±0.04) s, respectively. Supported by single-particle simulations, we conclude that the dominant mechanism limiting the confinement in this trap is scattering off of neutrals, which can lead to both radial transport and parallel losses onto the magnet surface. These results provide encouragement for plans to confine an electron-positron plasma in a levitated dipole trap.

Electro-optic Bdot probe measurement of magnetic fluctuations in plasma.

We propose a combined use of a Pockels electro-optic sensor with a pickup loop coil (Bdot probe) for the measurement of magnetic fluctuations in plasmas. In this method, induced fluctuating voltage on the coil loop is converted into an optical signal by a compact electro-optic sensor in the vicinity of the measurement point and is transferred across optical fiber that is unaffected by electric noise or capacitive load issues. Compared with conventional Bdot probes, the electro-optic Bdot probe (1) is electrically isolated and free from noise pickup caused by the metallic transmission line and (2) can be operated at a higher-frequency range because of the smaller capacitance of the operation circuit, both of which are suitable for many plasma experiments. Conversely, the sensitivity of the current electro-optic Bdot probe arrangement is still significantly lower than that of conventional Bdot probes. A preliminary measurement result with the electro-optic Bdot probe showed the detection of a magnetic fluctuation signal around the cyclotron frequency range in the RT-1 magnetospheric plasma experiment.

Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation.

Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1-deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin.Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation.

Magnetospheric vortex formation: self-organized confinement of charged particles.

A magnetospheric configuration gives rise to various peculiar plasma phenomena that pose conundrums to astrophysical studies; at the same time, innovative technologies may draw on the rich physics of magnetospheric plasmas. We have created a "laboratory magnetosphere" with a levitating superconducting ring magnet. Here we show that charged particles (electrons) self-organize a stable vortex, in which particles diffuse inward to steepen the density gradient. The rotating electron cloud is sustained for more than 300 s. Because of its simple geometry and self-organization, this system will have wide applications in confining single- and multispecies charged particles.

Structural transformations and anomalous viscosity in the B2O3 melt under high pressure.

Liquid B2O3 represents an archetypical oxide melt with a superhigh viscosity at the melting temperature. We present the results of the in situ x-ray diffraction study and the in situ viscosity measurements of liquid B2O3 under high pressure up to 8 GPa. Additionally, the 11B solid state NMR spectroscopy study of B2O3 glasses quenched from the melt at five different pressures has been carried out. Taken together, the results obtained provide understanding of the nature of structural transformations in liquid B2O3. The fraction of the boroxol rings in the melt structure rapidly decreases with pressure. From pressures of about 4.5 GPa, four-coordinated boron states begin to emerge sharply, reaching the fraction 40%-45% at 8 GPa. The viscosity of the B2O3 melt along the melting curve drops by 4 orders of magnitude as the pressure increases up to 5.5 GPa and remains unchanged on further pressure increase.

A levitated magnetic dipole configuration as a compact charged particle trap.

As a magnetic confinement configuration for electron-positron pair-plasmas, the APEX collaboration [T. S. Pedersen et al., New J. Phys. 14, 035010 (2012)] plans to construct a compact levitated dipole experiment with a high-temperature superconducting coil. In order to realize stable levitation of the dipole field coil, a simple feedback-controlled levitation system was constructed with conventional analog circuits. We report the properties of a prototype levitation system using a permanent magnet and compare its behavior to predictions from a stability analysis. We also present a practical review needed for the construction of a compact levitated dipole trap system based on the work of Morikawa et al. [Teion Kogaku, J. Cryo. Soc. Jpn. 39, 209 (2004)]. Numerical orbit analysis suggests improved confinement properties of charged particles in a dipole field trap by replacing the permanent magnet with a levitated superconducting coil magnet. Such a compact dipole field configuration is potentially applicable to the confinement of various charged particles including positrons and electrons.

CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase.

The human autoantigen CENP-C has been demonstrated by immunoelectron microscopy to be a component of the inner kinetochore plate. Here we have used antibodies raised against various portions of CENP-C to probe its function in mitosis. We show that nuclear microinjection of anti-CENP-C antibodies during interphase causes a transient arrest at the following metaphase. Injection of the same antibodies after the initiation of prophase, however, does not disrupt mitosis. Correspondingly, indirect immunofluorescence using affinity-purified human anti-CENP-C antibodies reveals that levels of CENP-C staining are reduced at centromeres in cells that were injected during interphase, but appear unaffected in cells which were injected during mitosis. Thus, we suggest that the injected antibodies cause metaphase arrest by reducing the amount of CENP-C at centromeres. Examination of kinetochores in metaphase-arrested cells by electron microscopy reveals that the number of trilaminar structures is reduced. More surprisingly, the few remaining kinetochores in these cells retain a normal trilaminar morphology but are significantly reduced in diameter. In cells arrested for extended periods, these small kinetochores become disrupted and apparently no longer bind microtubules. These observations are consistent with an involvement of CENP-C in kinetochore assembly, and suggest that CENP-C plays a critical role in both establishing and/or maintaining proper kinetochore size and stabilizing microtubule attachments. These findings also support the idea that proper assembly of kinetochores may be monitored by the cell cycle checkpoint preceding the transition to anaphase.

The clinical significance of serum procalcitonin levels following direct hemoperfusion with polymyxin B-immobilized fiber column in septic patients with colorectal perforation.

BACKGROUND: The efficacy of direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX) has already been demonstrated in clinical studies for the treatment of septic shock. However, serum procalcitonin levels following PMX remain unknown. METHODS: This prospective, multicenter, nonrandomized clinical study was performed at 12 institutions. Forty-five patients with severe sepsis or septic shock due to colorectal perforation underwent PMX. Patients' outcome as well as circulating levels of endotoxin, procalcitonin and IL-6 were monitored. RESULTS: Before surgery, procalcitonin level, but not endotoxin and IL-6 levels, was elevated according to patients' septic conditions. Procalcitonin was significantly and positively correlated with sequential organ failure assessment score. Circulating levels of procalcitonin peaked 24 h after PMX treatment. Change in serum procalcitonin level was significantly higher in nonsurvivors than survivors. Nine mortalities were observed within 28 days. The best predictor for 28-day mortality was procalcitonin >85.7 ng/ml at 24 h after PMX (area under the receiver operating characteristic curve: 0.808 +/- 0.105). CONCLUSIONS: Procalcitonin may be a good indicator of severity of sepsis secondary to colorectal perforation. Furthermore, procalcitonin level at 24 h after PMX appears to predict outcome after PMX. Therefore, procalcitonin may be a useful diagnostic marker to evaluate patients' condition in candidates for PMX treatment.

Slow Progression of Aortic Calcification Is a Potential Benefit of Pre-emptive Kidney Transplantation.

PURPOSE: Pre-emptive kidney transplantation (PKT) is expected to improve graft and cardiovascular event-free survival compared with standard kidney transplantation. Aortic calcification is reported to be closely associated with renal dysfunction and cardiovascular events; however, its implication in PKT recipients remains incompletely explored. This aim of this study was to evaluate whether PKT confers a protective effect on aortic calcification, renal function, graft survival, and cardiovascular event-free survival. METHODS: One hundred adult patients who underwent renal transplantation between January 1996 and March 2016 at Hirosaki University Hospital and Oyokyo Kidney Research Institute were included. Among them, 19 underwent PKT and 81 patients underwent pretransplant dialysis. We retrospectively compared pretransplant and post-transplant aortic calcification index (ACI), renal function (estimated glomerular filtration rate [eGFR]), and graft and cardiovascular event-free survivals between the 2 groups. RESULTS: The median age of this cohort was 45 years. Preoperative ACI was significantly lower in PKT recipients. There were no significant differences between the 2 groups regarding postoperative eGFR, graft survival, and cardiovascular event-free survival. However, the ACI progression rate (ΔACI/y) was significantly lower in PKT recipients than in those who underwent pretransplant dialysis. Higher ACI was significantly associated with poor cardiovascular event-free survival. CONCLUSIONS: PKT is beneficial in that it contributes to the slow progression of after transplantation. Although we could not observe significant differences in graft and cardiovascular event-free survivals between the 2 groups, slow progression of aortic calcification showed a potential to decrease cardiovascular events in PKT recipients during long-term follow-up.

Condyloma Acuminata of the Urethra in a Male Renal Transplant Recipient: A Case Report.

BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease associated with human papilloma virus (HPV). CA occurring in the urethra is rare and has not been reported in male renal transplant recipients. In addition, despite immunosuppressive conditions and increased risk of HPV-related malignant neoplasms in transplant recipients, HPV testing in male transplant recipients has been uncommon. Here we report a case of urethral CA in a male deceased donor renal transplantation recipient and discuss the importance of HPV testing in male transplant recipients. CASE PRESENTATION: A 33-year-old male deceased donor renal transplant recipient presented with miction pain 5 years after the transplantation. He reported repeated urinary tract infections with no sexual contact since the renal transplantation. Multiple papillary tumors in his penile urethra were detected by cystoscopy, and a biopsy sample was pathologically diagnosed with CA. Transurethral tumor resection was performed, and the tumors were completely resected. Additional HPV risk type screening with a urethral smear sample showed the prevalence of low-risk HPV. Although tacrolimus was switched to everolimus and imiquimod cream was administered, the tumors recurred 6 months after the resection, and a second resection was performed. No further recurrence has been observed for 1 year to date. CONCLUSION: As the urethral CA was possibly related to immunosuppressive conditions and a risk for HPV-related malignant neoplasm, the case required careful diagnosis, including HPV risk type. The methodology of sampling for HPV testing in men has not been established. This case suggests the necessity for further discussion about HPV testing in male transplant recipients.

Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2.

The yeast UBC9 gene encodes a protein with homology to the E2 ubiquitin-conjugating enzymes that mediate the attachment of ubiquitin to substrate proteins [1]. Depletion of Ubc9p arrests cells in G2 or early M phase and stabilizes B-type cyclins [1]. p18(Ubc9), the Xenopus homolog of Ubc9p, associates specifically with p88(RanGAP1) and p340(RanBP2) [2]. Ran-binding protein 2 (p340(RanBP2)) is a nuclear pore protein [3] [4], and p88(RanGAP1) is a modified form of RanGAP1, a GTPase-activating protein for the small GTPase Ran [2]. It has recently been shown that mammalian RanGAP1 can be conjugated with SUMO-1, a small ubiquitin-related modifier [5-7], and that SUMO-1 conjugation promotes RanGAP1's interaction with RanBP2 [2,5,6]. Here we show that p18(Ubc9) acts as an E2-like enzyme for SUMO-1 conjugation, but not for ubiquitin conjugation. This suggests that the SUMO-1 conjugation pathway is biochemically similar to the ubiquitin conjugation pathway but uses a distinct set of enzymes and regulatory mechanisms. We also show that p18(Ubc9) interacts specifically with the internal repeat domain of RanBP2, which is a substrate for SUMO-1 conjugation in Xenopus egg extracts.

Identification of overlapping DNA-binding and centromere-targeting domains in the human kinetochore protein CENP-C.

The kinetochore in eukaryotes serves as the chromosomal site of attachment for microtubules of the mitotic spindle and directs the movements necessary for proper chromosome segregation. In mammalian cells, the kinetochore is a highly differentiated trilaminar structure situated at the surface of the centromeric heterochromatin. CENP-C is a basic, DNA-binding protein that localizes to the inner kinetochore plate, the region that abuts the heterochromatin. Microinjection experiments using antibodies specific for CENP-C have demonstrated that this protein is required for the assembly and/or stability of the kinetochore as well as for a timely transition through mitosis. From these observations, it has been suggested that CENP-C is a structural protein that is involved in the organization or the kinetochore. In this report, we wished to identify and map the functional domains of CENP-C. Analysis of CENP-C truncation mutants expressed in vivo demonstrated that CENP-C possesses an autonomous centromere-targeting domain situated at the central region of the CENP-C polypeptide. Similarly, in vitro assays revealed that a region of CENP-C with the ability to bind DNA is also located at the center of the CENP-C molecule, where it overlaps the centromere-targeting domain.

Molecular-network-ionic structure transitions in liquid AlCl(3) and ZnCl(2) halogenides under pressure.

We present the in situ high-pressure-high-temperature x-ray diffraction study of the liquid AlCl(3) and ZnCl(2) halogenides having a quasi-molecular network structure in liquid state at normal pressure. These liquids are intermediate between pure covalent and ionic melts. Structural study of these liquid halogenides is indicative of a rapid and strong breakdown of an intermediate-range order in a tetrahedral network of melts for the initial pressure range, 0-2.5 GPa for AlCl(3) and 0-1.8 GPa for ZnCl(2), and points to rather sharp transitions in liquids with the formation of a short-range order structure similar to ionic melt structures around 4 GPa for AlCl(3) and 3 GPa for ZnCl(2). Thus, pseudo-covalent liquid halogenides like AlCl(3) and ZnCl(2) provide testimony to two phenomena under high pressures, namely, a gradual decay of structural correlations in the tetrahedral network of the melt and a sharp transition from molecular-network to ionic structure in liquid on further compression. Such a two-stage structural transformation under pressure is the general feature for a wide class of simple melts, including most of the pseudo-covalent halogenides.

Direct and indirect association of the small GTPase ran with nuclear pore proteins and soluble transport factors: studies in Xenopus laevis egg extracts.

Ran is a small GTPase that is required for protein import, mRNA export, and the maintenance of nuclear structures. To gain a better understanding of Ran's role in the nucleus, we have sought to use Xenopus egg extracts for the purification and characterization of proteins from egg extracts bound with a high affinity to a glutathione-S-transferase-Ran fusion protein (GST-Ran). We found that GST-Ran associates specifically with at least 10 extract proteins. We determined the identifies of six Ran-interacting proteins (Rips), and found that they include RanBP2/Nup358, Nup153, Importin beta, hsc70, RCC1, and RanBP1. On the basis of peptide sequence, a seventh Rip (p88) seems to be similar but not identical to Fug1/RanGAP1, the mammalian Ran-GTPase-activating protein. Gel filtration analysis of endogenous extract proteins suggests that Importin beta acts as a primary GTP-Ran effector. Both Ran and Importin beta are coimmunoprecipitated by anti-p340RanBP2 antibodies in the presence of nonhydrolyzable GTP analogues, suggesting that Ran-Importin beta complexes interact with p340RanBP2. Two other Rips, p18 and p88, are coprecipitated with p340RanBP2 in a nucleotide-independent manner. Analysis of the Ran-GTPase pathway in Xenopus extracts allows the examination of interactions between Ran-associated proteins under conditions that resemble in vivo conditions more closely than in assays with purified components, and it thereby allows additional insights into the molecular mechanism of nuclear transport.

[Preoperative pulseless electrical activity of acute type A aortic dissection; report of a case].

An 80-year-old man with acute type A aortic dissection, who was preoperatively observed in the intensive care unit, suddenly became unresponsive. The patient was immediately intubated, but a pulse check was delayed because the cardiac monitor seemingly showed a normal sinus rhythm. Bedside echocardiography, while continuing cardiopulmonary resuscitation, revealed massive pericardial effusion. It indicated the patient's cardiac arrest was pulseless electrical activity (PEA) due to cardiac tamponade. After pericardiocentesis, a perfusion rhythm was restored with palpable distal pulse. He successfully underwent a prosthetic graft replacement of the ascending aorta and was discharged after physical rehabilitation.

Electro-optic probe measurements of electric fields in plasmas.

The direct measurements of high-frequency electric fields in a plasma bring about significant advances in the physics and engineering of various waves. We have developed an electro-optic sensor system based on the Pockels effect. Since the signal is transmitted through an optical fiber, the system has high tolerance for electromagnetic noises. To demonstrate its applicability to plasma experiments, we report the first result of measurement of the ion-cyclotron wave excited in the RT-1 magnetosphere device. This study compares the results of experimental field measurements with simulation results of electric fields in plasmas.

Method for efficient storage and transportation of sputum specimens for molecular testing of tuberculosis.

SETTING: The polymerase chain reaction (PCR) is a highly sensitive method for the detection of Mycobacterium tuberculosis and is available in most countries, though to a lesser extent in rural areas. OBJECTIVE: To amplify M. tuberculosis DNA sequences of sputum spotted on FTA cards and compare them with the results of microscopic examination among culture-positive samples. DESIGN: A total of 102 sputum specimens of TB patients in treatment were spotted on FTA cards and stored at room temperature until DNA analysis. We assessed the IS6110 region of M. tuberculosis. The efficacy of the PCR assay for the direct detection of M. tuberculosis was evaluated and compared with the results of cultures (Middlebrook 7H9 broth) and smears of fresh sputum specimens. RESULTS: We were able to detect 10 fg/microl of mycobacterial DNA even after 6 months in storage. The PCR sensitivity and specificity using the FTA card system were 82% and 96%, while microscopic examination showed 41% and 95%, respectively. CONCLUSION: The FTA card system for the storage of bacterial DNA from sputum samples should be considered for the molecular diagnosis of tuberculosis. Samples can easily be obtained from geographically isolated populations and shipped by mail for accurate molecular diagnosis.

Clinical and epidemiological studies of eicosapentaenoic acid (EPA) in Japan.

From 1950 to 1980, the gross alteration in dietary habit in Japan was noted. Intake of total calories has markedly increased. This could be most likely due to a remarkable increase in intake of fat, especially animal fat, egg and milk products. A marked decrease of mortality rate due to cerebral hemorrhage and in contrast a marked increase of mortality rate due to cerebral infarction and ischemic heart disease were noted. An epidemiological study of the intake of fish meat (EPA intake) and the mortality rate of adult diseases was performed in a fishing area and in a farming area in Chiba Prefecture. Intake of fish meat (EPA) by the residents of the fishing area was 2-3 times higher than by the residents of the farming area. The mortality rate due to ischemic heart disease and cerebral vascular diseases tended to be lower in the fishing area than in the farming area. EPA manufactured from sardine oil was orally given to normal subjects and to patients with cerebro- and cardiovascular diseases for 4-16 weeks. Significantly decreased platelet aggregation, decreased platelet retention, lowered whole blood viscosity, prolonged bleeding time, increased erythrocyte deformability, improvement of hyperlipidemia, and clinical improvement in some patients were noted. 12-Lipoxygenase metabolites of EPA (12-HPEPE) and arachidonic acid (12-HPETE) have an equipotent inhibitory action on platelet function.