Learning Promotes Subfield-Specific Synaptic Diversity in Hippocampal CA1 Neurons.

The hippocampus is functionally heterogeneous between the dorsal and ventral subfields with left-right asymmetry. To determine the possible location of contextual memory, we performed an inhibitory avoidance task to analyze synaptic plasticity using slice patch-clamp technique. The training bilaterally increased the AMPA/NMDA ratio at dorsal CA3-CA1 synapses, whereas the training did not affect the ratio at ventral CA3-CA1 synapses regardless of the hemisphere. Moreover, sequential recording of miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents from the same CA1 neuron clearly showed learning-induced synaptic plasticity. In dorsal CA1 neurons, the training dramatically strengthened both excitatory and inhibitory postsynaptic responses in both hemispheres, whereas the training did not promote the plasticity in either hemisphere in ventral CA1 neurons. Nonstationary fluctuation analysis further revealed that the training bilaterally increased the number of AMPA or GABAA receptor channels at dorsal CA1 synapses, but not at ventral CA1 synapses, suggesting functional heterogeneity of learning-induced receptor mobility. Finally, the performance clearly impaired by the bilateral microinjection of plasticity blockers in dorsal, but not ventral CA1 subfields, suggesting a crucial role for contextual learning. The quantification of synaptic diversity in specified CA1 subfields may help us to diagnose and evaluate cognitive disorders at the information level.

Static and Dynamical Properties of the Spin-1/2 Equilateral Triangular-Lattice Antiferromagnet Ba_{3}CoSb_{2}O_{9}.

We present single-crystal neutron scattering measurements of the spin-1/2 equilateral triangular-lattice antiferromagnet Ba_{3}CoSb_{2}O_{9}. Besides confirming that the Co^{2+} magnetic moments lie in the ab plane for zero magnetic field and then determining all the exchange parameters of the minimal quasi-2D spin Hamiltonian, we provide conclusive experimental evidence of magnon decay through observation of intrinsic line broadening. Through detailed comparisons with the linear and nonlinear spin-wave theories, we also point out that the large-S approximation, which is conventionally employed to predict magnon decay in noncollinear magnets, is inadequate to explain our experimental observation. Thus, our results call for a new theoretical framework for describing excitation spectra in low-dimensional frustrated magnets under strong quantum effects.

Constraints on new gravitylike forces in the nanometer range.

We report on a new constraint on gravitylike short-range forces, in which the interaction charge is mass, obtained by measuring the angular distribution of 5 Å neutrons scattering off atomic xenon gas. Around 10^{7} scattering events were collected at the 40 m small angle neutron scattering beam line located at the HANARO research reactor of the Korean Atomic Energy Research Institute. The extracted coupling strengths of new forces in the Yukawa-type parametrization are g[over ^]^{2}=(0.2±6.8±2.0)×10^{-15} GeV^{-2} and g[over ^]^{2}=(-5.3±9.0_{-2.8}^{+2.7})×10^{-17} GeV^{-2} for interaction ranges of 0.1 and 1.0 nm, respectively. These strengths correspond to 95% confidence level limits of g^{2}<(1.4±0.2)×10^{-14} GeV^{-2} and g^{2}<(1.3±0.2)×10^{-16} GeV^{-2}, improving the current limits for interaction ranges between 4 and 0.04 nm by a factor of up to 10.

Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in interleukin-1 receptor antagonist knockout mice.

The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody against A. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-α) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-κB ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A. actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1α mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.

Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice. MATERIALS AND METHODS: 21-day-old female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed. RESULTS: In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression. CONCLUSION: Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.

Observation of the spatial distribution of gravitationally bound quantum states of ultracold neutrons and its derivation using the Wigner function.

Ultracold neutrons (UCNs) can be bound by the potential of terrestrial gravity and a reflecting mirror. The wave function of the bound state has characteristic modulations. We carried out an experiment to observe the vertical distribution of the UCNs above such a mirror at the Institut Laue-Langevin in 2011. The observed modulation is in good agreement with that prediction by quantum mechanics using the Wigner function. The spatial resolution of the detector system is estimated to be 0.7 µm. This is the first observation of gravitationally bound states of UCNs with submicron spatial resolution.

Experimental validation of a novel compact focusing scheme for future energy-frontier linear lepton colliders.

A novel scheme for the focusing of high-energy leptons in future linear colliders was proposed in 2001 [P. Raimondi and A. Seryi, Phys. Rev. Lett. 86, 3779 (2001)]. This scheme has many advantageous properties over previously studied focusing schemes, including being significantly shorter for a given energy and having a significantly better energy bandwidth. Experimental results from the ATF2 accelerator at KEK are presented that validate the operating principle of such a scheme by demonstrating the demagnification of a 1.3 GeV electron beam down to below 65 nm in height using an energy-scaled version of the compact focusing optics designed for the ILC collider.

Lipopolysaccharide of Aggregatibacter actinomycetemcomitans up-regulates inflammatory cytokines, prostaglandin E2 synthesis and osteoclast formation in interleukin-1 receptor antagonist-deficient mice.

BACKGROUND AND OBJECTIVE: The interleukin (IL)-1 receptor antagonist (Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is unclear whether the IL-1Ra plays a protective role in periodontal disease. The purpose of this study was to compare IL-1Ra knockout (KO) and wild-type (WT) mice in regard to proinflammatory cytokine production, osteoclast formation and bone resorption in response to periodontal bacterial lipopolysaccharide (LPS). MATERIAL AND METHODS: Peritoneal macrophages (Mφs) were obtained from 13-wk-old IL-1Ra KO and WT mice. Peritoneal Mφs were cultured with or without 10 µg/mL of Aggregatibacter actinomycetemcomitans LPS for 24 h. The levels of IL-1alpha (IL-1α), IL-1beta (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 were measured in periotoneal Mφs supernatant fluid (PM-SF) using an ELISA. Bone marrow cells were obtained from the mice and stimulated with PM-SF for 9 d, then stained with TRAP. The frequency of TRAP-positive multinucleated giant cell formation was calculated based on a fusion index. PM-SF-stimulated calvarial bone resorption was analyzed using micro-computed tomography, and calvarial histological analysis was performed using hematoxylin and eosin and TRAP staining. The expression of cyclooxygenase-2 (Cox2), prostanoid receptor EP4 (Ep4) and Rank mRNAs in bone marrow cells were measured using real-time quantitative PCR, while prostaglandin E2 (PGE2 ) production was determined by ELISA. RESULTS: The levels of IL-1α, IL-1ß, TNF-α and IL-6 in IL-1Ra KO mice PM-SF stimulated with A. actinomycetemcomitans LPS were significantly increased by approximately 4- (p < 0.05), 5- (p < 0.05), 1.3- (p < 0.05) and 6- (p < 0.05) fold, respectively, compared with the levels in WT mice. Moreover, osteoclast formation, expression of Rank, Ep4 and Cox2 mRNAs and production of PGE2 were significantly increased by approximately 2- (p < 0.05), 1.6- (p < 0.05), 2.5- (p < 0.05), 1.6- (p < 0.05) and 1.9- (p < 0.05) fold, respectively, in IL-1Ra KO mice stimulated with A. actinomycetemcomitans LPS compared with WT mice. CONCLUSION: IL-1Ra regulates IL-1 activity and appears to reduce the levels of other inflammatory cytokines, including TNF-α and IL-6, while it also reduces expression of the EP4 receptor related to prostanoid sensitivity and osteoclast formation. These results suggest that IL-1Ra is an important molecule for inhibition of inflammatory periodontal bone resorption.

Formation of magnetic microphases in Ca3Co2O6.

We study a frustrated quantum Ising model relevant for Ca3Co2O6 that consists of a triangular lattice of weakly coupled ferromagnetic chains. According to our quantum Monte Carlo simulations, the chains become ferromagnetic and form a three-sublattice "up-up-down" structure for T≤T(CI). In contrast, long-wavelength spin-density-wave microphases are stabilized along the chains for T(CI)

Multiferroic behavior in trimerized Mott insulators.

We demonstrate multiferroic behavior in trimerized Mott insulators through the interplay between spins and electric dipole moments resulting from electronic charge fluctuations in frustrated units. The model consists of stacked triangular layers of trimers with small intertrimer exchange interactions J' and J''. Ferroelectric states coexist with ferro- or antiferromagnetic orderings depending on the value of the magnetic field H and the sign of the interlayer exchange J''. The electric polarization undergoes abrupt changes as a function of H.

Socioeconomic inequalities in toothbrushing behaviours in young children: a children's lifestyle survey in a representative population of A city, Okinawa prefecture, Japan.

PURPOSE: We have less understanding of which socioeconomic status (SES) indicators may be reflective of latent socioeconomic inequalities in toothbrushing behaviours, especially finishing-toothbrushing by parents in young children. The aim of this study was to reveal the socioeconomic inequalities in children's toothbrushing and finishing-toothbrushing by parents and if it varies by SES indicators. METHODS: We used data from 'Survey on Children's Life' conducted by A city of Okinawa Prefecture, Japan. The multiple imputed data of 902 (boys, 453) included self-reported children's toothbrushing behaviour and finishing-toothbrushing by parents in three-to six-year-old children. SES was assessed using self-reported household income and parental educational attainment. Absolute and relative inequalities in toothbrushing behaviours were quantified using the slope index of inequality (SII) and relative index of inequality (RII), respectively. RESULTS: There were significant absolute and relative inequalities of children's toothbrushing for household income (SII and RII were 0.241 and 2.73, respectively), of finishing-toothbrushing by parents for household income (SII and RII were 0.133 and 3.28, respectively), and educational attainment (SII and RII were 0.166 and 5.55, respectively). The same inequality trends were observed after adjusting for covariates (child's age and sex, family structure, breakfast and dinner frequency, and sleep duration). CONCLUSION: Socioeconomic inequalities in children's toothbrushing and finishing-toothbrushing by parents varied according to SES indicators.

Comparison of haemodynamic responses to tracheal intubation using the Airway Scope(®) and Macintosh laryngoscope in normotensive and hypertensive patients.

We compared the effects of the Airway Scope(®) on haemodynamic responses during tracheal intubation with those of direct laryngoscopy in normotensive and hypertensive patients. The systolic blood pressure, diastolic blood pressures and heart rate were recorded: (a) before anaesthesia; (b) immediately before intubation; (c) at intubation; and (d) 1, 2, 3, 4 and 5 min after intubation. In normotensive patients, the increase in blood pressure and heart rate over time were significantly lower with the Airway Scope than with the Macintosh laryngoscope (p < 0.003). In hypertensive patients, however, there was no difference in the changes over time in any of these haemodynamic measures between the two devices (p > 0.05). We conclude that the Airway Scope attenuates haemodynamic responses to tracheal intubation in comparison with the laryngoscope in normotensive but not in hypertensive patients. You can respond to this article at http://www.anaesthesiacorrespondence.com.

The C. elegans unc-18 gene encodes a protein expressed in motor neurons.

The C. elegans unc-18 gene is required to maintain normal acetylcholine levels. We determined the complete structure of an unc-18 cDNA that encodes a protein of 591 highly charged and hydrophilic amino acids. The protein shows sequence similarity with elements of the secretory pathway in the yeast S. cerevisiae. Antibodies raised against a portion of the unc-18-encoded protein (UNC-18) detected a 68 kd soluble antigen on immunoblots and intensely stained all vertical cord motor neurons in situ. These findings suggest that UNC-18 participates in the axonal transport system and influences the acetylcholine flow in motor neurons.

Soluble interleukin-1 receptor type II levels in gingival crevicular fluid in aggressive and chronic periodontitis.

BACKGROUND: Interleukin (IL)-1 is closely related to the initiation and progression of periodontal disease. IL-1 levels in the gingival crevicular fluid (GCF) of subjects with periodontitis are higher than those in periodontally healthy controls, and the levels of IL-1 correlate with disease severity. However, soluble IL-1 receptor type II (sIL-1RII), which acts as a decoy receptor for IL-1s, has not been investigated in detail in periodontal disease. The purpose of this study was to measure sIL-1RII levels in the GCF of subjects with chronic or aggressive periodontitis; the correlation between the sIL-1RII levels in GCF and clinical parameters also was examined. METHODS: IL-1beta and sIL-1RII were measured in 64 GCF samples collected from 47 subjects with chronic periodontitis (CP) and 17 subjects with aggressive periodontitis (AgP). The clinical characteristics of each site were recorded at the time of GCF sampling. IL-1beta and sIL-1RII were measured by specific non-cross-reactive enzyme-linked immunosorbent assay. RESULTS: The disease severity was comparable in CP and AgP. IL-1beta was detected in 98% of CP GCF samples and 88% of AgP GCF samples. sIL-1RII was detected in 55% of CP GCF samples and 35% of AgP GCF samples. However, the concentrations of IL-beta and sIL-1RII detected in GCF from subjects with CP or AgP were similar. CONCLUSION: sIL-1RII was detected more often in CP GCF than in AgP GCF, and there was no correlation between GCF sIL-1RII concentration and clinical parameters.

The nature of spin excitations in the one-third magnetization plateau phase of Ba3CoSb2O9.

Magnetization plateaus in quantum magnets-where bosonic quasiparticles crystallize into emergent spin superlattices-are spectacular yet simple examples of collective quantum phenomena escaping classical description. While magnetization plateaus have been observed in a number of spin-1/2 antiferromagnets, the description of their magnetic excitations remains an open theoretical and experimental challenge. Here, we investigate the dynamical properties of the triangular-lattice spin-1/2 antiferromagnet Ba3CoSb2O9 in its one-third magnetization plateau phase using a combination of nonlinear spin-wave theory and neutron scattering measurements. The agreement between our theoretical treatment and the experimental data demonstrates that magnons behave semiclassically in the plateau in spite of the purely quantum origin of the underlying magnetic structure. This allows for a quantitative determination of Ba3CoSb2O9 exchange parameters. We discuss the implication of our results to the deviations from semiclassical behavior observed in zero-field spin dynamics of the same material and conclude they must have an intrinsic origin.

Author Correction: The nature of spin excitations in the one-third magnetization plateau phase of Ba3CoSb2O9.

The original version of this Article omitted the following from the Acknowledgements: 'J. Ma's primary affiliation is Shanghai Jiao Tong University.' This has been corrected in both the PDF and HTML versions of the Article.

Thymic hyperplasia in patients with Graves' disease. Identification of thyrotropin receptors in human thymus.

Thymic size and density were studied in 23 untreated patients with Graves' disease and 38 control subjects using computed tomography. Both thymic size and density were higher in untreated patients with Graves' disease than in control subjects in the age-matched group. After treatment with antithyroid drugs, both thymic size and density were significantly reduced, with a concomitant decrease in thyrotropin receptor antibodies. PCR of human thymic cDNA using primers for human thyrotropin receptor amplified a fragment in a size expected for the receptor, and its nucleotide sequence was identical to human thyrotropin receptor cDNA in the thyroid. Northern blot analysis of human thymic poly(A)+ RNA demonstrated the presence of the full length form of thyrotropin receptor mRNA. Western blot analysis of human thymic membrane using anti-thyrotropin receptor peptide antibodies demonstrated a band of 100 kD that was also observed in the thyroid membrane. Immunohistochemistry of thymic tissue using mouse antihuman thyrotropin receptor monoclonal antibodies demonstrated the immunostaining of epithelial cells. These results indicate that thymic hyperplasia is apparently associated with Graves' disease and suggest that thymic thyrotropin receptor may act as an autoantigen that may be involved in the pathophysiology of development of Graves' disease.

High-dose chemotherapy and autologous peripheral blood stem cell transfusion for adult and adolescent patients with small round cell sarcomas.

The treatment of small-round-cell tumors (SRCT) in adult patients remains a challenge to clinicians. In the present study, we analyzed the feasibility and efficacy of high-dose chemotherapy (HDCT) followed by autologous peripheral blood stem-cell rescue as a consolidation therapy exclusively for patients with good disease control through a single regimen of induction chemotherapy and local therapy. Twenty-one patients (12 females, median age 22.0 years) were analyzed, including seven cases with rhabdomyosarcoma (RMS) and 14 cases with Ewing's family tumors (EFT). Overall, survival was 46% and failure-free survival (FFS) was 33% at 3 years. Patients with EFT had better FFS than those with RMS, with an estimated 3-year FFS of 50% (P<0.01). There was a single case of possible treatment-related death and two cases of secondary malignancies. This study cannot conclusively determine the beneficial effects of HDCT for improving treatment outcomes in adult SRCTs due to the small number of subjects. However, study findings suggest that a subgroup of patients with EFT may obtain prolonged survival benefits from this therapy.

Ordering phenomena in a heterostructure of frustrated and unfrustrated triangular-lattice Ising layers.

We study critical and magnetic properties of a bilayer Ising system consisting of two triangular planes A and B, with the antiferromagnetic (AF) coupling J_{A} and the ferromagnetic (FM) one J_{B} for the respective layers, which are coupled by the interlayer interaction J_{AB} by using Monte Carlo simulations. When J_{A} and J_{B} are of the same order, the unfrustrated FM plane orders first at a high temperature T_{c1}∼J_{B}. The spontaneous FM order then exerts influence on the other frustrated AF plane as an effective magnetic field, which subsequently induces a ferrimagnetic order in this plane at low temperatures below T_{c2}. When short-range order is developed in the AF plane while the influence of the FM plane is still small, there appears a preemptive Berezinskii-Kosterlitz-Thouless-type pseudocritical crossover regime just above the ferrimagnetic phase transition point, where the short-distance behavior up to a rather large length scale exponentially diverging in ∝J_{A}/T is controlled by a line of Gaussian fixed points at T=0. In the crossover region, a continuous variation in the effective critical exponent 4/9≲η^{eff}≲1/2 is observed. The phase diagram by changing the ratio J_{A}/J_{B} is also investigated.

Regulation of gibberellin biosynthesis by light.

Phytochromes regulate transcript levels of gibberellin biosynthesis enzymes, GA 20-oxidases and/or GA 3beta-hydroxylases, in germinating lettuce and Arabidopsis seeds and in de-etiolating pea seedlings. Feedback regulation of GA biosynthesis by active GA is well established, but other mechanisms for regulation of these biosynthetic genes also exist, as this feedback does not operate on a GA 3beta-hydroxylase gene of Arabidopsis during seed germination.