High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Prognostic factors for idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and intravenous steroids.

OBJECTIVE: This study evaluated the prognosis of idiopathic sudden sensorineural hearing loss when treated with hyperbaric oxygen therapy and intravenous steroids. METHODS: The clinical data for 334 patients with idiopathic sudden sensorineural hearing loss treated by hyperbaric oxygen therapy and intravenous steroids at our hospital were retrospectively reviewed. These data included the initial averaged five-frequency hearing level, patient age, interval between onset of symptoms and treatment, vertigo as a complication, and co-existence of diabetes mellitus. RESULTS: The overall improvement rate was 69.2 per cent, including better improvement (25.5 per cent), good improvement (21.0 per cent) and fair improvement (22.7 per cent). CONCLUSION: Hyperbaric oxygen therapy appears to confer a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss. If performed early, hyperbaric oxygen therapy may bring about hearing improvement in many patients who are unresponsive to initial therapy.

Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems.

Glycyrrhiza uralensis roots used in this study were produced using novel cultivation systems, including artificial hydroponics and artificial hydroponic-field hybrid cultivation. The equivalency between G. uralensis root extracts produced by hydroponics and/or hybrid cultivation and a commercial Glycyrrhiza crude drug were evaluated for both safety and efficacy, and there were no significant differences in terms of mutagenicity on the Ames tests. The levels of cadmium and mercury in both hydroponic roots and crude drugs were less than the limit of quantitation. Arsenic levels were lower in all hydroponic roots than in the crude drug, whereas mean lead levels in the crude drug were not significantly different from those in the hydroponically cultivated G. uralensis roots. Both hydroponic and hybrid-cultivated root extracts showed antiallergic activities against contact hypersensitivity that were similar to those of the crude drug extracts. These study results suggest that hydroponic and hybrid-cultivated roots are equivalent in safety and efficacy to those of commercial crude drugs. Further studies are necessary before the roots are applicable as replacements for the currently available commercial crude drugs produced from wild plant resources.

Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA Synthesis and Possesses Nucleoprotein Chaperone Activity.

The genome of influenza virus (viral RNA [vRNA]) is associated with the nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical viral ribonucleoprotein (vRNP) complexes. The NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using a Saccharomyces cerevisiae replicon system and a single-gene deletion library of Saccharomyces cerevisiae (T. Naito, Y. Kiyasu, K. Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata, Proc Natl Acad Sci USA, 104:18235-18240, 2007, https://doi.org/10.1073/pnas.0705856104). In infected Prp18 knockdown (KD) cells, the synthesis of vRNA, cRNA, and viral mRNAs was reduced. Prp18 was found to stimulate in vitro viral RNA synthesis through its interaction with NP. Analyses using in vitro RNA synthesis reactions revealed that Prp18 dissociates newly synthesized RNA from the template after the early elongation step to stimulate the elongation reaction. We found that Prp18 functions as a chaperone for NP to facilitate the formation of NP-RNA complexes. Based on these results, it is suggested that Prp18 accelerates influenza virus RNA synthesis as an NP chaperone for the processive elongation reaction. IMPORTANCE: Templates for viral RNA synthesis of negative-stranded RNA viruses are not naked RNA but rather RNA encapsidated by viral nucleocapsid proteins forming vRNP complexes. However, viral basic proteins tend to aggregate under physiological ionic strength without chaperones. We identified the pre-mRNA processing factor Prp18 as a stimulatory factor for influenza virus RNA synthesis. We found that one of the targets of Prp18 is NP. Prp18 facilitates the elongation reaction of viral polymerases by preventing the deleterious annealing of newly synthesized RNA to the template. Prp18 functions as a chaperone for NP to stimulate the formation of NP-RNA complexes. Based on these results, we propose that Prp18 may be required to maintain the structural integrity of vRNP for processive template reading.

Survival outcomes after surgical resection of pulmonary metastases of head and neck tumours.

BACKGROUND: There is limited information available regarding the benefits and outcomes of resection of pulmonary metastases arising from head and neck cancers. METHODS: A retrospective review was performed of 21 patients who underwent resection of pulmonary metastases of primary head and neck malignancies at Hamamatsu University Hospital. Clinical staging, treatment methods, pathological subtype (particularly squamous cell carcinoma), disease-free interval and overall survival were evaluated. RESULTS: The 5- and 10-year overall survival rates of the study participants were 67.0 per cent and 55.0 per cent, respectively, as determined by the Kaplan-Meier method. The prognosis for patients with a disease-free interval of less than 24 months was poor compared to those with a disease-free interval of greater than 24 months (p = 0.0234). CONCLUSION: Patients with short disease-free intervals, and possibly those who are older than 60 years, should be categorised as having severe disease. However, pulmonary metastases from head and neck malignancies are potentially curable by surgical resection.

Lattice Boltzmann simulations of droplet formation in confined channels with thermocapillary flows.

Based on mesoscale lattice Boltzmann simulations with the "Shan-Chen" model, we explore the influence of thermocapillarity on the breakup properties of fluid threads in a microfluidic T-junction, where a dispersed phase is injected perpendicularly into a main channel containing a continuous phase, and the latter induces periodic breakup of droplets due to the cross-flowing. Temperature effects are investigated by switching on-off both positive-negative temperature gradients along the main channel direction, thus promoting a different thread dynamics with anticipated-delayed breakup. Numerical simulations are performed at changing the flow rates of both the continuous and dispersed phases, as well as the relative importance of viscous forces, surface tension forces, and thermocapillary stresses. The range of parameters is broad enough to characterize the effects of thermocapillarity on different mechanisms of breakup in the confined T-junction, including the so-called "squeezing" and "dripping" regimes, previously identified in the literature. Some simple scaling arguments are proposed to rationalize the observed behavior, and to provide quantitative guidelines on how to predict the droplet size after breakup.

Discovering metabolic indices for early detection of squash (Cucurbita maxima) storage quality using GC-MS-based metabolite profiling.

Squash (Cucubita maxima) cultivars with good storage qualities are needed for breeding to improve poor crop supply during winter in Japan. We measured changes in squash constituents during different storage periods to identify compounds that were suitable to be used as indices of storage quality. Principal components analysis of compounds at 1-5 months after harvest showed that PC1 scores were lower for cultivars with a higher rather than lower SQ (storage quality) ranks. Partial least-squares regression analysis was performed using the peak areas of all compounds identified from the 15 cultivars at 1 month after harvest as explanation variables and SQ as the target variable. Variable influence on projection scores and rank correlation coefficients were higher for arabinose and xylose, which showed less temporal change during the storage period; hence, they were considered to be suitable indicators for storage evaluation. These data will be useful for future studies aiming to improve storage quality of squash.

The efficacy of add-on tacrolimus for minor flare in patients with systemic lupus erythematosus: a retrospective study.

OBJECTIVE: We have assessed the effectiveness of tacrolimus for minor flares in systemic lupus erythematosus (SLE) patients. METHODS: The medical records of 313 patients were retrospectively reviewed over a period of seven years, from 2006 to 2013. We enrolled patients with minor flare treated with add-on tacrolimus, without glucocorticoid (GC) intensification (tacrolimus group). Minor flare was defined as a ≥ 1-point increase in a total score between 3 and 11 in the SLE Disease Activity Index (SLEDAI). We enrolled as controls patients who were administered increased doses of GC for minor flare (GC group). All patients were followed for one year. The primary outcome measure was the proportion of responders. RESULTS: There were 14 eligible patients in the tacrolimus group and 20 eligible patients in the GC group. The mean SLEDAI at flare tended to be higher in the tacrolimus group than in the GC group (7.5 vs. 6.2, p = 0.085). A mean dose of 1.6 mg tacrolimus/day was administered for flare, while the mean GC dose was 13.7 mg/day in the GC group. The proportion of responders was 86% (12/14) in the tacrolimus group and 75% (15/20) in the GC group (p = 0.67). The mean dose of GC at 12 months was higher in the GC group than in the tacrolimus group (9.7 mg/day vs. 7.1 mg/day, p < 0.05). Only one patient discontinued tacrolimus because of fatigue after three months. CONCLUSION: Adding tacrolimus without increasing the GC dose may provide an effective treatment option for minor flares in patients with SLE.

Relationship between the Peripheral Lymphocyte Response to Mycophenolic Acid in vitro and the Level of ATP in Peripheral CD4+ Lymphocytes before and after Renal Transplantation.

OBJECTIVE: The lymphocyte immunosuppressant sensitivity test has been used to predict the pharmacodynamics of immunosuppressive drugs for the purpose of preventing acute rejection and infection after renal transplantation. On the other hand, measuring the ATP levels in peripheral CD4+ lymphocytes is also able to monitor the risks of rejection and infection in transplant recipients. In the present study, we examined the relationship between the mycophenolic acid pharmacodynamics and the ATP levels in peripheral lymphocytes before and after renal transplantation. METHODS: We examined both the pharmacological efficacy of mycophenolic acid and the lymphocyte ATP levels before and 2, 4 and 6 weeks after the operation in 20 renal transplant recipients. The drug's pharmacological efficacy was evaluated by the 50% inhibitory concentration of the drug against the in vitro proliferation of peripheral blood lymphocytes activated by T cell mitogen. The ATP levels in peripheral CD4+ lymphocytes were measured by the Immuknow assay kit. The relationships between the mycophenolic acid pharmacodynamics and ATP levels in peripheral lymphocytes were examined in these recipients. RESULTS: The immunosuppressive effects of mycophenolic acid against mitogen-activated lymphocyte proliferation were significantly and positively correlated with the lymphocyte ATP levels, but only at 6 weeks after transplantation. The relationship was not significant before or at 2 or 4 weeks after the operation. CONCLUSION: Our present data raised the possibility that evaluating the pharmacological efficacy of mycophenolic acid pre-transplantation and monitoring the ATP level 6 weeks after transplantation can predict the risk of rejection and/or infection in renal transplant recipients.

Rehabilitation for paraplegia caused by neuromyelitis optica: a case report.

STUDY DESIGN: Single case report. OBJECTIVE: We present a case of paraplegia due to neuromyelitis optica (NMO) with poor rehabilitation outcome. SETTING: University hospital, Japan. CASE REPORT: A 27-year-old woman with NMO presented with T5 paraplegia of ASIA impairment scale grade A. Spinal cord magnetic resonance imaging revealed a lesion spanning C3 to L1 level. After acute phase treatment, flaccid paraplegia below T5 and a T2-weighted hyperintense lesion from T6 to T10 level remained. Rehabilitation aimed at independence of activities of daily living with wheelchair assistance, including transfer activity, was provided for 19 months. However, flaccid paralysis of the trunk and limbs persisted, and safe independent transfer was not achieved. CONCLUSION: Spinal lesions spanning many vertebral segments, a characteristic of NMO, can cause extensive flaccid paralysis of the trunk and limbs. Rehabilitation may achieve poorer functional recovery than that for spinal cord injury.

Association study of genetic variants on chromosome 7q31 with susceptibility to normal tension glaucoma in a Japanese population.

The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms; that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma.

A design of backing seat and gasket assembly in diamond anvil cell for accurate single crystal x-ray diffraction to 5 GPa.

We designed a new cell assembly of diamond anvil cells for single crystal x-ray diffraction under pressure and demonstrate the application of the cell to the crystallographic studies for ice VI and ethanol high-pressure (HP) phase at 0.95(5) GPa and 1.95(2) GPa, respectively. The features of the assembly are: (1) the platy anvil and unique-shaped backing seat (called as "Wing seat") allowing the extremely wide opening angle up to ±65°, (2) the PFA-bulk metallic glass composite gasket allowing the easy attenuation correction and less background. Thanks to the designed assembly, the R(int) values after attenuation corrections are fairly good (0.0125 and 0.0460 for ice VI and ethanol HP phase, respectively), and the errors of the refined parameters are satisfactory small even for hydrogen positions, those are comparable to the results which obtained at ambient conditions. The result for ice VI is in excellent agreement with the previous study, and that for ethanol HP phase has remarkable contributions to the revision to its structure; the H12 site, which makes gauche molecules with O1, C2, and C3 sites, may not exist so that only trans conformers are present at least at 1.95(2) GPa. The accurate intensities using the cell assembly allow us to extract the electron density for ethanol HP phase by the maximum entropy method.

Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex.

Sulfatide (ST) is a sphingolipid with an important role in the central nervous system as a major component of the myelin sheath. ST contains a structurally variable ceramide moiety, with a fatty acid substituent of varying carbon-chain length and double-bond number. Hydroxylation at the α-2 carbon position of the fatty acid is found in half the population of ST molecules. Recent genetic studies of fatty acid 2-hydroxylase (FA2H) indicate that these hydroxylated sphingolipids influence myelin sheath stability. However, their distribution is unknown. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables the analysis of distinct distributions of individual ST molecular species in tissue section. We examined human cerebral cortex tissue sections with MALDI-IMS, identifying and characterizing the distributions of 14 ST species. The distribution analysis reveals that the composition ratios of non-hydroxylated/hydroxylated STs are clearly reversed at the border between white and gray matter; the hydroxylated group is the dominant ST species in the gray matter. These results suggest that hydroxylated STs are highly expressed in oligodendrocytes in gray matter and might form stable myelin sheaths. As a clinical application, we analyzed a brain with Alzheimer's disease (AD) as a representative neurodegenerative disease. Although previous studies of AD pathology have reported that the amount of total ST is decreased in the cerebral cortex, as far as the compositional distributions of STs are concerned, AD brains were similar to those in control brains. In conclusion, we suggest that MALDI-IMS is a useful tool for analysis of the distributions of various STs and this application might provide novel insight in the clinical study of demyelinating diseases.

Negative regulation of NaF-induced apoptosis by Bad-CAII complex.

Fluoride is used to prevent caries in dentistry. However, its mechanism of cytotoxicity induction is unclear. This study was undertaken to determine whether sodium fluoride (NaF) induces apoptosis in human oral cells and if so, whether Bad protein is involved in the process. NaF showed higher cytotoxicity and apoptosis-inducing activity against human oral squamous cell carcinoma cells (HSC-2) than against human gingival fibroblasts (HGF). Western blot analysis showed that NaF enhanced the expression and dephosphorylation of Bad protein. This study demonstrates for the first time that Bad protein forms a complex with carbonic anhydrase II (CAII), and NaF stimulates the detachment of CAII from the Bad-CAII complex and the replacement by the formation of Bad-Bcl-2 complex. Knockdown of Bad and CAII mRNA by siRNA inhibited and enhanced the NaF-induced caspase activation, respectively. The present study suggests that CAII negatively regulates the NaF-induced apoptosis by forming a complex with Bad.

Over-expression of the LTC4 synthase gene in mice reproduces human aspirin-induced asthma.

BACKGROUND: The pathogenesis of aspirin-induced asthma (AIA) is presumed to involve the aspirin/non-steroidal anti-inflammatory drug (NSAID)-induced abnormal metabolism of arachidonic acid, resulting in an increase in 5-lipoxygenase (5-LO) metabolites, particularly leukotriene C(4) (LTC(4) ). However, the role of LTC(4) in the development of AIA has yet to be conclusively demonstrated. OBJECTIVE: The aim of this study was to evaluate the contribution of the lipid product LTC(4) secreted by the 5-LO pathway to the pathogenesis of AIA. METHODS: To evaluate antigen-induced airway inflammation, the concentrations of T-helper type 2 cytokine in bronchoalveolar lavage fluid (BALF) obtained from LTC(4) synthase-transgenic (Tg) and wild-type (WT) mice after challenge with ovalbumin were measured. Subsequently, the ex vivo and in vivo effects of the NSAID sulpyrine were investigated in these Tg and WT mice by measuring the secretion of LTC(4) from sulpyrine-treated BAL cells and the levels of LTC(4) in BALF following challenge with sulpyrine. Finally, the sulpyrine-induced airway response by the administration of pranlukast, an antagonist of the cysteinyl (cs)-LT1 receptor, was analysed. RESULTS: The concentrations of IL-4, -5, and -13 in BALF from Tg mice were significantly higher than those in WT mice. In addition, sulpyrine augmented the secretion of LTC(4) in BALF and by BAL cells in Tg mice, but not in WT mice. Additionally, the increased airway resistance induced by sulpyrine could be reduced by treatment with pranlukast. Furthermore, the secretion of LTC(4) from mast cells, eosinophils, and macrophages was increased in the allergen-stimulated LTC(4) synthase gene Tg mice, even in the absence of sulpyrine, as well as in BAL cells after sulpyrine. CONCLUSION AND CLINICAL RELEVANCE: The over-expression of the LTC(4) synthase in a mouse asthma model also replicates the key features of AIA. And our study supports that cys-LTs play a major role in the pathogenesis of AIA in patients with chronic asthma.