Monoclonal anti-dsDNA antibody 2C10 escorts DNA to intracellular DNA sensors in normal mononuclear cells and stimulates secretion of multiple cytokines implicated in lupus pathogenesis.

There have been many studies on the mechanisms of internalization of DNA-anti-DNA immune complexes by cells, including the one used for rheumatoid factor-expressing mouse B cells. In parallel, studies on the role of intracellular DNA sensors in the pathogenesis of systemic lupus erythematosus (SLE) have been conducted, including the one using a mouse model lacking one of the sensors. These and other data have established a framework for understanding the pathogenic role of anti-DNA antibodies, but studies on normal cells are limited. Here, we used the monoclonal anti-dsDNA antibody 2C10, 2-kbp dsDNA and healthy human peripheral blood mononuclear cells (PBMCs) to test whether and how 2C10 and/or DNA cause pathology in normal cells. We found that on culture with PBMCs, 2C10 preferentially entered monocytes and that DNA enhanced this internalization. In contrast, DNA alone was not significantly internalized by monocytes, but 2C10 facilitated its internalization. This was suppressed by cytochalasin D, but not by methyl-ß-cyclodextrin, chloroquine or an Fc blocker, suggesting the involvement of macropinocytosis in this process. Internalization of 2C10 and DNA together resulted in production of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1ß, IL-6, IL-10 and IL-33 by PBMCs. Cytokine production was suppressed by chloroquine and shikonin, but not by RU.521, suggesting dependence on activation of the Toll-like receptor (TLR)-9 and absent in melanoma 2 (AIM-2) pathways. These results established a simple model to demonstrate that anti-DNA antibodies can cause dysregulation of cytokine network mimicking systemic lupus erythematosus in culture of normal PBMCs, and emphasize again the importance of maintaining anti-DNA antibodies at low levels by treatment.

Correction to: Comprehensive genetic analyses using targeted next-generation sequencing and genotype-phenotype correlations in 53 Japanese patients with osteogenesis imperfecta.

The original article has been corrected.

Anti-ß2 -glycoprotein I antibody with DNA binding activity enters living monocytes via cell surface DNA and induces tissue factor expression.

Autoantibodies characteristic for anti-phospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are anti-ß2 -glycoprotein I (ß2 GPI) antibodies and anti-DNA antibodies, respectively, and almost half of APS cases occur in SLE. Anti-ß2 GPI antibodies are recognized to play a pivotal role in inducing a prothrombotic state, but the precise mechanism has not been fully elucidated. In a widely accepted view, binding of anti-ß2 GPI antibodies to cell surface ß2 GPI in monocytes and endothelial cells triggers the Toll-like receptor 4-myeloid differentiation primary response 88 (TLR)-4-MyD88) signaling pathway which leads to activation of p38 mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinases (MEK-1/ERK) and/or nuclear factor kappa B (NF-κB) and expression of tissue factor (TF). However, resting cells do not express substantial amounts of TLR-4. Previously, we generated a mouse monoclonal anti-ß2 GPI antibody WB-6 and showed that it induced a prothrombotic state - including TF expression on circulating monocytes - in normal mice. In the current study, we aimed to clarify the mechanism of interaction between WB-6 and resting monocytes, and found that WB-6 exhibits binding activity to DNA and enters living monocytes or a monocytic cell line and, to a lesser extent, vascular endothelial cells. Treatment of the cells with DNase I reduced the internalization, suggesting the involvement of cell surface DNA in this phenomenon. Monocytes harboring internalized WB-6 expressed TF and tumor necrosis factor (TNF)-α which, in turn, stimulated endothelial cells to express intercellular adhesion molecule 1 (ICAM-I) and vascular cell adhesion molecule 1 (VCAM-I). These results suggest the possibility that a subset of anti-ß2 GPI antibodies with dual reactivity to DNA possesses ability to stimulate DNA sensors in the cytoplasm, in addition to the cell surface receptor-mediated pathways, leading to produce proinflammatory and prothrombotic states.

Comprehensive genetic analyses using targeted next-generation sequencing and genotype-phenotype correlations in 53 Japanese patients with osteogenesis imperfecta.

To elucidate mutation spectrum and genotype-phenotype correlations in Japanese patients with OI, we conducted comprehensive genetic analyses using NGS, as this had not been analyzed comprehensively in this patient population. Most mutations were located on COL1A1 and COL1A2. Glycine substitutions in COL1A1 resulted in the severe phenotype. INTRODUCTION: Most cases of osteogenesis imperfecta (OI) are caused by mutations in COL1A1 or COL1A2, which encode α chains of type I collagen. However, mutations in at least 16 other genes also cause OI. The mutation spectrum in Japanese patients with OI has not been comprehensively analyzed, as it is difficult to identify using classical Sanger sequencing. In this study, we aimed to reveal the mutation spectrum and genotype-phenotype correlations in Japanese patients with OI using next-generation sequencing (NGS). METHODS: We designed a capture panel for sequencing 15 candidate OI genes and 19 candidate genes that are associated with bone fragility or Wnt signaling. Using NGS, we examined 53 Japanese patients with OI from unrelated families. RESULTS: Pathogenic mutations were detected in 43 out of 53 individuals. All mutations were heterozygous. Among the 43 individuals, 40 variants were identified including 15 novel mutations. We found these mutations in COL1A1 (n = 30, 69.8%), COL1A2 (n = 12, 27.9%), and IFITM5 (n = 1, 2.3%). Patients with glycine substitution on COL1A1 had a higher frequency of fractures and were more severely short-statured. Although no significant genotype-phenotype correlation was observed for bone mineral density, the trabecular bone score was significantly lower in patients with glycine substitutions. CONCLUSION: We identified pathogenic mutations in 81% of our Japanese patients with OI. Most mutations were located on COL1A1 and COL1A2. This study revealed that glycine substitutions on COL1A1 resulted in the severe phenotype among Japanese patients with OI.

Increased number of eosinophils in ascites is associated with intestinal anisakidosis.

The aim of this study was to evaluate the association between eosinophils in ascites and the diagnosis of intestinal anisakidosis in patients with peritoneal signs on physical examination. We reviewed retrospectively 16 patients diagnosed with intestinal anisakidosis, evaluated between 2012 and 2015. All patients had ingested raw anchovies. The analysis of ascites fluid in ten of these patients was compared with that of 15 patients with ascites and other abdominal pathology (except liver cirrhosis). All patients had an increased number of white blood cells in the ascites fluid. The eosinophil count was significantly higher in patients with intestinal anisakidosis (P < 0.01). All patients had a good outcome. Increased eosinophils in ascites fluid is strongly associated with the diagnosis of intestinal anisakidosis.

Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.

The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.

No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology.

STUDY QUESTION: Does letrozole use increase the risk of major congenital anomalies and adverse pregnancy and neonatal outcomes in fresh, single-embryo transfer? SUMMARY ANSWER: Letrozole significantly decreases the risk of miscarriage and does not increase the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in patients undergoing ART. WHAT IS KNOWN ALREADY: Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, its safety in terms of pregnancy and neonatal outcomes is unclear. STUDY DESIGN SIZE, DURATION: This retrospective cohort study used data from the Japanese national ART registry from 2011 to 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3136 natural cycles and 792 letrozole-induced cycles associated with fresh, single-embryo transfer and resulting in a clinical pregnancy were included in the analysis. The main pregnancy outcomes were miscarriage, ectopic pregnancy and still birth, and the neonatal outcomes were preterm delivery, low birth weight, small/large for gestational age and major congenital anomalies. Terminated pregnancies were included in the analysis of major congenital anomalies. Odds ratios (ORs) and 95% CIs were calculated using multivariate logistic regression analysis adjusted for maternal age and calendar year. MAIN RESULTS AND THE ROLE OF CHANCE: The risk of miscarriage was significantly lower in women administered letrozole (adjusted OR [aOR], 0.37, 95% CI, 0.30-0.47, P < 0.001). There was no significant difference in the overall risk of major congenital anomalies between the two groups (natural cycle 1.5% vs letrozole 1.9%, aOR, 1.24, 95% CI, 0.64-2.40, P = 0.52), and no increased risk for any specific organ system. Subgroup analysis demonstrated that the risk of major congenital anomalies was not increased in patients who underwent either in vitro fertilization or ICSI, or in those who received early cleavage stage or blastocyst embryo transfer. All other pregnancy and neonatal outcomes were comparable between the two groups. LIMITATIONS REASONS FOR CAUTION: Despite the large sample size, we were only able to rule out the possibility that letrozole might cause large increases in birth-defect risks in ART patients. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that letrozole stimulation reduces the risk of miscarriage, with no increase in the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in women undergoing ART. Letrozole may thus be a safe option for mild ovarian stimulation. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Pregnancy and neonatal outcomes following letrozole use in frozen-thawed single embryo transfer cycles.

STUDY QUESTION: Are pregnancy and neonatal outcomes following letrozole use comparable with natural and HRT cycles in patients undergoing single frozen-thawed embryo transfer (FET)? SUMMARY ANSWER: Letrozole use was significantly associated with higher rates of clinical pregnancy, clinical pregnancy with fetal heart beat and live birth, and with a lower rate of miscarriage, compared with natural and HRT cycles. WHAT IS KNOWN ALREADY: Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, the effect of letrozole on pregnancy and neonatal outcomes in FET are not well known. STUDY DESIGN SIZE, DURATION: A retrospective cohort study was conducted using data from the Japanese national ART registry between 2012 and 2013. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 110 722 single FET cycles with letrozole (n = 2409), natural (n = 41 470) or HRT cycles (n = 66 843) were included. The main outcomes were the rates of clinical pregnancy, clinical pregnancy with fetal heart beat, miscarriage and live birth. Adjusted odds ratios and relative risks (RRs) were calculated using a generalized estimating equation adjusting for correlations within clinics. MAIN RESULTS AND THE ROLE OF CHANCE: The rates of clinical pregnancy, clinical pregnancy with fetal heart beat, and live birth were significantly higher, while the rate of miscarriage was significantly lower in the letrozole group compared with the natural and HRT groups. In blastocyst stage transfers, the adjusted RRs for clinical pregnancy with fetal heart beat of letrozole compared with natural and HRT cycles were 1.48 (95% CI: 1.41-1.55) and 1.62 (95% CI: 1.54-1.70), respectively. Similarly, the adjusted RRs of letrozole for miscarriage compared with natural and HRT cycles were 0.91 (95% CI: 0.88-0.93) and 0.84 (95% CI: 0.82-0.87), respectively. Neonatal outcomes were mostly similar in letrozole, natural and HRT cycles. LIMITATIONS REASONS FOR CAUTION: Important limitations of this study included the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration of letrozole intake. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that letrozole use may improve clinical pregnancy, clinical pregnancy with fetal heart beat, and live births and reduce the risk of miscarriage in patients undergoing single FET cycles. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Mendelian inheritance, genetic linkage, and genotypic disequilibrium for nine microsatellite loci in Cariniana estrellensis (Raddi) Kuntze (Lecythidaceae).

Cariniana estrellensis is one of the largest trees found in Brazilian tropical forests. The species is typical of advanced stages of succession, characteristic of climax forests, and essential in genetic conservation and environmental restoration plans. In this study, we assessed Mendelian inheritance, genetic linkage, and genotypic disequilibrium in nine microsatellite loci for a C. estrellensis population. We sampled and genotyped 285 adult trees and collected seeds from 20 trees in a fragmented forest landscape in Brazil. Based on maternal genotypes and their seeds, we found no deviation from the expected 1:1 Mendelian segregation and no genetic linkage between pairwise loci. However, for adults, genotypic disequilibrium was detected for four pairs of loci, suggesting that this result was not caused by genetic linkage. Based on these results, we analyzed microsatellite loci that are suitable for use in population genetic studies assessing genetic diversity, mating system, and gene flow in C. estrellensis populations.

Subjective insomnia is associated with low sleep efficiency and fatigue in middle-aged women.

OBJECTIVES: Many middle-aged women are affected by sleep disturbance. We investigated how subjective insomnia is associated with objective sleep parameters and other background characteristics. METHODS: This cross-sectional study used baseline data obtained from 95 women aged 40-59 years who participated in another study assessing the effects of a dietary supplement. Participants wore an actigraph unit for 3 days to collect information concerning physical activities and objective sleep parameters and were then evaluated for body composition, cardiovascular parameters, and menopausal symptoms including insomnia and fatigue, and lifestyle factors. Stratifying Athens Insomnia Scale scores as low (0-5 points, control group) and high (≥ 6 points, subjective insomnia group), we sought to identify the parameters that are independently associated with subjective insomnia. RESULTS: Women with subjective insomnia (n = 30) had lower sleep efficiency than did the controls. They were also older; had more live births, lower height, higher body mass index, lower ankle brachial index, and more severe menopausal symptoms including fatigue; took more naps; smoked more cigarettes; and more of them were full-time workers. Multivariate logistic regression analysis revealed that low sleep efficiency (adjusted odds ratio, 1.44 per 1% decrease in sleep efficiency; 95% confidence interval 1.06-2.05) and fatigue assessed with Brief Fatigue Inventory (BFI) (adjusted odds ratio, 1.57 per 1-point increase in BFI score; 95% confidence interval 1.19-2.13) were independent contributors to subjective insomnia. CONCLUSIONS: Low sleep efficiency and feeling of fatigue were found to be independently associated with subjective insomnia in middle-aged women.

Hand-assisted laparoscopic transhiatal esophagectomy with a systematic procedure for en bloc infracarinal lymph node dissection.

Laparoscopic transhiatal esophagectomy is a minimally invasive approach for esophageal cancer. However, a transhiatal procedure has not yet been established for en bloc mediastinal dissection. The purpose of this study was to present our novel procedure, hand-assisted laparoscopic transhiatal esophagectomy, with a systematic procedure for en bloc mediastinal dissection. The perioperative outcomes of patients who underwent this procedure were retrospectively analyzed. Transhiatal subtotal mobilization of the thoracic esophagus with en bloc lymph node dissection distally from the carina was performed according to a standardized procedure using a hand-assisted laparoscopic technique, in which the operator used a long sealing device under appropriate expansion of the operative field by hand assistance and long retractors. The thoracoscopic procedure was performed for upper mediastinal dissection following esophageal resection and retrosternal stomach roll reconstruction, and was avoided based on the nodal status and operative risk. A total of 57 patients underwent surgery between January 2012 and June 2013, and the transthoracic procedure was performed on 34 of these patients. In groups with and without the transthoracic procedure, total operation times were 370 and 216 minutes, blood losses were 238 and 139 mL, and the numbers of retrieved nodes were 39 and 24, respectively. R0 resection rates were similar between the groups. The incidence of recurrent laryngeal nerve palsy was significantly higher in the group with the transthoracic procedure, whereas no significant differences were observed in that of pneumonia between these groups. The hand-assisted laparoscopic transhiatal method, which is characterized by a systematic procedure for en bloc mediastinal dissection supported by hand and long device use, was safe and feasible for minimally invasive esophagectomy.

Short Communication Mendelian inheritance, linkage, and genotypic disequilibrium in microsatellite loci of Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae-Caesalpinioideae).

Hymenaea stigonocarpa is a deciduous and monoecious Neotropical tree species pollinated by bats. Due to overexploitation and habitat destruction, the population size has drastically diminished in nature. No previous study has investigated Mendelian inheritance, linkage, and genotypic disequilibrium in the available microsatellite markers in this species. So, our aim was to estimate these parameters using six microsatellite loci in a sample of 470 adults and 219 juveniles from two populations of H. stigonocarpa. In addition, 30 seeds per tree from 35 seed-trees were collected. Each seed was kept record of the seed-trees and fruit origin. Based on the six microsatellite loci, we found that only 10.6% of the cases showed significant deviations from Mendelian segregation and 15.3% showed linkage. We detected no evidence of genotypic disequilibrium between the loci in the adult trees or juveniles. Thus, our results suggest that these loci can be used with great accuracy in future genetic analyses of H. stigonocarpa populations.

Adsorption efficiency of natural materials for low-concentration cesium in solution.

In this study, several natural materials were investigated in order to clarify their potential use as cesium (Cs) adsorbents in situ. Four materials--carbonized rice hull, beech sawdust, oak sawdust, and charcoal (Japanese cedar)--which were previously shown to have Cs adsorption capabilities, were examined. Cs adsorption experiments were conducted using different initial Cs and adsorbent concentrations. The physical properties, adsorption isotherms, and adsorption processes were then examined, so as to exploit the Cs adsorption characteristics in the field. Based on these findings, carbonized rice hull and beech sawdust were selected as effective Cs adsorbents. It was found that these materials show continuous and stable Cs adsorption rates for different initial Cs concentrations. The adsorption efficiency of these two adsorption materials in combination was considered, and it was shown that the adsorption isotherms for carbonized rice hull and beech sawdust follow the Freundlich model. Furthermore, the beech sawdust adsorption process exhibited better agreement with the calculated values obtained via the adsorption rate model and the adsorption kinetics model than did the carbonized rice hull adsorption.

Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolated from a university teaching hospital in Japan.

Clostridium difficile infection control strategies require an understanding of its epidemiology. In this study, we analysed the toxin genotypes of 130 non-duplicate clinical isolates of C. difficile from a university hospital in Tokyo, Japan. Multilocus sequence typing (MLST) and eBURST analysis were performed for these isolates and nine strains previously analysed by polymerase chain reaction (PCR) ribotyping. Minimum inhibitory concentrations (MICs) were determined for six antibiotics, and the bacterial resistance mechanisms were investigated. Ninety-five toxigenic strains (73%), including seven tcdA-negative, tcdB-positive and cdtA/cdtB-negative strains (A(-)B(+)CDT(-)) and three A(+)B(+)CDT(+) strains, and 35 (27%) non-toxigenic strains, were classified into 23 and 12 sequence types, respectively. Of these, sequence type (ST)17 (21.8%) was the most predominant. MLST and eBURST analysis showed that 139 strains belonged to seven groups and singletons, and most A(+)B(+)CDT(-) strains (98%, 89/91) were classified into group 1. All isolates were susceptible to metronidazole, vancomycin and meropenem; the ceftriaxone, clindamycin and ciprofloxacin resistance rates were 49, 59 and 99%, respectively. Resistance rates to ceftriaxone and clindamycin were higher in toxigenic strains than in non-toxigenic strains (P < 0.001). All ST17 and ST81 strains were resistant to these antibiotics. The clindamycin- and fluoroquinolone-resistant strains carried erm(B) and mutations in GyrA and/or GyrB, respectively. To our knowledge, this is the first MLST-based study of the molecular epidemiology of toxigenic and non-toxigenic strains in Japan, providing evidence that non-toxigenic and toxigenic strains exhibit high genetic diversity and that toxigenic strains are more likely than non-toxigenic strains to exhibit multidrug resistance.

Influence of surgical orthodontic treatment on masticatory function in skeletal Class III patients.

Skeletal Class III patients exhibit malocclusion characterised by Angle Class III and anterior crossbite, and their occlusion shows total or partially lateral crossbite of the posterior teeth. Most patients exhibit lower bite force and muscle activity than non-affected subjects. While orthognathic surgery may help improve masticatory function in these patients, its effects have not been fully elucidated. The aims of the study were to evaluate jaw movement and the electromyographic (EMG) activity of masticatory muscles before and after orthognathic treatment in skeletal Class III patients in comparison with control subjects with normal occlusion. Jaw movement variables and EMG data were recorded in 14 female patients with skeletal Class III malocclusion and 15 female controls with good occlusion. Significant changes in jaw movement, from a chopping to a grinding pattern, were observed after orthognathic treatment (closing angle P < 0.01; cycle width P < 0.01), rendering jaw movement in the patient group similar to that of the control group. However, the grinding pattern in the patient group was not as broad as that of controls. The activity indexes, indicating the relative contributions of the masseter and temporalis muscles (where a negative value corresponds to relatively more temporalis activity and vice versa) changed from negative to positive after treatment (P < 0.05), becoming similar to those of control subjects. Our findings suggest that orthognathic treatment in skeletal Class III patients improves the masticatory chewing pattern and muscle activity. However, the chewing pattern remains incomplete compared with controls.

Hepatic arterial infusion chemotherapy with cisplatin before radical local treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival.

BACKGROUND: It has not yet been determined whether hepatic arterial infusion (HAI) chemotherapy improves survival in patients with early hepatocellular carcinoma (HCC). We evaluated the effectiveness of HAI with high-concentration cisplatin (DDP-H) for the treatment of HCC by comparing outcomes between patients who received HAI with DDP-H before radical local treatment of early-stage HCC [Japan Integrated Staging (JIS) score 0/1] and patients who did not receive HAI chemotherapy. PATIENTS AND METHODS: Survival was analyzed in 114 patients with early-stage HCC who underwent radical local treatment. The patients were divided into two groups: a HAI group (n = 79) who received DDP-H infusion into the whole liver via the proper hepatic artery, and a non-HAI group (n = 35) who did not receive HAI chemotherapy. RESULTS: The cumulative survival rates at 1, 3, and 5 years were 77.4%, 69.2%, and 55.3% in the non-HAI group and 97.4%, 87.0%, and 84.4% in the HAI group, respectively. Survival time prolonged significantly in the HAI group compared with the non-HAI group (log-rank test: P = 0.023; generalized Wilcoxon test: P = 0.012) Multivariate analysis using the Cox proportional hazards model identified HAI with DDP-H as the most important factor affecting survival. CONCLUSIONS: Whole-liver HAI with DDP-H before radical local treatment can improve the prognosis of patients with early-stage HCC.

Down-regulated expression of monocyte/macrophage major histocompatibility complex receptors in human and mouse monocytes by expression of their ligands.

Mouse monocyte/macrophage major histocompatibility complex (MHC) receptor 1 (MMR1; or MMR2) specific for H-2D(d) (or H-2K(d) ) molecules is expressed on monocytes from non-H-2D(d) (or non-H-2K(d) ), but not those from H-2D(d) (or H-2K(d) ), inbred mice. The MMR1 and/or MMR2 is essential for the rejection of H-2D(d) - and/or H-2K(d) -transgenic mouse skin onto C57BL/6 (H-2D(b) K(b) ) mice. Recently, we found that human leucocyte antigen (HLA)-B44 was the sole ligand of human MMR1 using microbeads that had been conjugated with 80 types of HLA class I molecules covering 94·2% (or 99·4%) and 92·4% (or 96·2%) of HLA-A and B molecules of Native Americans (or Japanese), respectively. In the present study, we also explored the ligand specificity of human MMR2 using microbeads. Microbeads coated with HLA-A32, HLA-B13 or HLA-B62 antigens bound specifically to human embryonic kidney (HEK)293T or EL-4 cells expressing human MMR2 and to the solubilized MMR2-green fluorescent protein (GFP) fusion protein; and MMR2(+) monocytes from a volunteer bound HLA-B62 molecules with a Kd of 8·7 × 10(-9) M, implying a three times down-regulation of MMR2 expression by the ligand expression. H-2K(d) (or H-2D(d) ) transgene into C57BL/6 mice down-regulated not only MMR2 (or MMR1) but also MMR1 (or MMR2) expression, leading to further down-regulation of MMR expression. In fact, monocytes from two (i.e. MMR1(+) /MMR2(+) and MMR1(-) /MMR2(-) ) volunteers bound seven to nine types of microbeads among 80, indicating ≤ 10 types of MMR expression on monocytes. The physiological role of constitutive MMRs on monocytes possibly towards allogeneic (e.g. fetal) cells in the blood appears to be distinct from that of inducible MMRs on macrophages toward allografts in tissue.

Abrupt transition from ferromagnetic to antiferromagnetic of interfacial exchange in perpendicularly magnetized L1(0)-MnGa/FeCo tuned by Fermi level position.

An abrupt transition of the interfacial exchange coupling from ferromagnetic to antiferromagnetic was observed in the interface of perpendicularly magnetized L10-MnGa/Fe1-xCox epitaxial bilayers when x was around 25%. By considering the special band structure of the MnGa alloy, we present a model explaining this transition by the spin-polarization reversal of Fe1-xCox alloys due to the rise of the Fermi level as the Co content increases. The effect of interfacial exchange coupling on the coercive force (Hc) and the spin-dependent tunneling effect in perpendicular magnetic tunnel junctions (pMTJs) based on the coupled composite were also studied. Changes from the normal spin valve to inverted magnetoresistance loops corresponding to the coupling transition were observed in pMTJs with MnGa/Fe1-xCox as an electrode.

Non-Gilbert-damping Mechanism in a Ferromagnetic Heusler Compound Probed by Nonlinear Spin Dynamics.

The nonlinear decay of propagating spin waves in the low-Gilbert-damping Heusler film Co_{2}Mn_{0.6}Fe_{0.4}Si is reported. Here, two initial magnons with frequency f_{0} scatter into two secondary magnons with frequencies f_{1} and f_{2}. The most remarkable observation is that f_{1} stays fixed if f_{0} is changed. This indicates, that the f_{1} magnon mode has the lowest instability threshold, which, however, cannot be understood if only Gilbert damping is present. We show that the observed behavior is caused by interaction of the magnon modes f_{1} and f_{2} with the thermal magnon bath. This evidences a significant contribution of the intrinsic magnon-magnon scattering mechanisms to the magnetic damping in high-quality Heusler compounds.

First molar cross-bite is more closely associated with a reverse chewing cycle than anterior or pre-molar cross-bite during mastication.

A posterior cross-bite is defined as an abnormal bucco-lingual relationship between opposing molars, pre-molars or both in centric occlusion. Although it has been reported that patients with unilateral posterior cross-bite often show unique chewing patterns, the relationship between the form of cross-bite and masticatory jaw movement remains unclear in adult patients. The objective of this study was to investigate masticatory jaw movement among different forms of cross-bite. One hundred and one adults were recruited in this study: 27 had unilateral first molar cross-bite (MC group); 28, unilateral pre-molar cross-bite (PC group); 23, anterior cross-bite (AC group); and 23, normal occlusion (control group). Masticatory jaw movement of the lower incisor point was recorded with six degrees of freedom jaw-tracking system during unilateral mastication. Our results showed that the reverse chewing ratio during deliberate unilateral mastication was significantly larger in the MC group than in the PA (P < 0.001), AC (P < 0.001) and control (P < 0.001) groups. These findings suggest that compared to the anterior or pre-molar cross-bite, the first molar cross-bite is more closely associated with a higher prevalence of a reverse chewing cycle.