Magnetically Hidden State on the Ground Floor of the Magnetic Devil's Staircase.

We investigated the low-temperature and high-field thermodynamic and ultrasonic properties of SrCu_{2}(BO_{3})_{2}, which exhibits various plateaux in its magnetization curve above 27 T, called a magnetic Devil's staircase. The results of the present study confirm that magnetic crystallization, the first step of the staircase, occurs above 27 T as a first-order transition accompanied by a sharp singularity in heat capacity C_{p} and a kink in the elastic constant. In addition, we observe a thermodynamic anomaly at lower fields around 26 T, which has not been previously detected by any magnetic probes. At low temperatures, this magnetically hidden state has a large entropy and does not exhibit Schottky-type gapped behavior, which suggests the existence of low-energy collective excitations. Based on our observations and theoretical predictions, we propose that magnetic quadrupoles form a spin-nematic state around 26 T as a hidden state on the ground floor of the magnetic Devil's staircase.

Hydride-Reduced Eu2SrFe2O6: A T-to-T' Conversion Enabling Fe2+ in Square-Planar Coordination.

Low-temperature reaction of A-site-ordered layered perovskite Eu2SrFe2O7 (T structure) with CaH2 induces a shift in the Eu2O2 slabs to form Eu2SrFe2O6 with a T' structure (I4/mmm space group) in which only the Fe cation is reduced. Contrary to the previously reported T' structures with Jahn-Teller-active d9 cations (Cu2+ and Ni+), stabilization of Eu2SrFe2O6 with the Fe2+ (d6) cation reflects the stability of the FeO4 square-planar unit. The stability of T'-type Eu2SrFe2O6 over a T-type polymorph is confirmed by density functional theory calculations, revealing the dz2 occupancy for the T' structure. Eu2SrFe2O6 has a bilayer magnetic framework with an Fe-O-Fe superexchange J∥ and an Fe-Fe direct exchange J⊥ (where J∥ > J⊥), which broadly explains the observed TN of 390-404 K. Interestingly, the magnetic moments of Eu2SrFe2O6 lie in the ab plane, in contrast to the structurally similar Sr3Fe2O4Cl2 having an out-of-plane spin alignment.

Inhibitory effects of mycosporine-2-glycine isolated from a halotolerant cyanobacterium on protein glycation and collagenase activity.

Mycosporine-2-glycine (M2G), isolated from the halotolerant cyanobacterium Aphanothece halophytica, was purified and characterized in order to determine its utility as a cosmetic and pharmaceutical ingredient. M2G efficiently inhibited protein crosslinking. The inhibitory activity of M2G was significantly greater than that of the well-known Maillard reaction inhibitor aminoguanidine. In addition, M2G and other known mycosporine-like amino acids inhibited bacterial collagenase activity. To the best of our knowledge, this is the first report describing that M2G specifically inhibits the formation of advanced glycation end-products (AGEs), which play a critical role in ageing process and age-related diseases. These observations indicate that M2G may have potential therapeutic applications by suppressing the formation of AGEs and inhibiting excess collagenase activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Mycosporine-like amino acids (MAAs) are known as multifunctional natural compounds. The MAA mycosporine-2-glycine (M2G), isolated from the halotolerant cyanobacterium Aphanothece halophytica, has potential therapeutic applications for the prevention of skin ageing. Purified M2G was endotoxin-free. M2G had greater inhibitory activity of protein cross-linking compared with well-known inhibitor, aminoguanidine and hindered bacterial collagenase activity. The mechanisms for these inhibitory activities of M2G are discussed in this study.

Requirement of alkanes for salt tolerance of Cyanobacteria: characterization of alkane synthesis genes from salt-sensitive Synechococcus elongatus PCC7942 and salt-tolerant Aphanothece halophytica.

Cyanobacteria have been attracting great interest in the research area of biofuel production. All Cyanobacteria contain C15 -C19 hydrocarbons, but physiological roles of hydrocarbons remain to be clarified. Recently, two universal but mutually exclusive hydrocarbon production pathways in Cyanobacteria were discovered. In this study, we constructed a deletion mutant of alkane synthesis genes in fresh water cyanobacterium Synechococcus elongates PCC 7942. The mutant was incapable to produce alkanes and exhibited normal growth phenotype at low salinity. But, the mutant became salt sensitive. Overexpression of alkane synthesis genes from halotolerant Aphanothece halophytica in Synechococcus PCC7942 restored the growth defect. The alkane synthesis gene from halotolerant cyanobacterium A. halophytica was salt induced and produced a significant amount of alkanes at high salinity. These results indicate the requirement of alkanes for salt tolerance, and the alkane synthesis genes from A. halophytica could be a promising candidate for future biofuel application. SIGNIFICANCE AND IMPACT OF THE STUDY: Cyanobacteria have been attracting great interest in the research area of biofuel production. All Cyanobacteria contain C15 -C19 hydrocarbons, but physiological roles of hydrocarbons remain to be clarified. In this study, it was found that the deletion mutant of alkane synthesis genes in fresh water cyanobacterium Synechococcus elongates PCC 7942 was incapable to produce alkanes and salt sensitive. The alkane synthesis gene from halotolerant cyanobacterium Aphanothece halophytica was salt induced and produced a significant amount of alkanes at high salinity. These results demonstrate the alkane synthesis genes from A. halophytica could be a promising candidate for future biofuel application.

High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients.

BACKGROUND: Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma. METHODS: One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations. RESULTS: High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 -3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma. CONCLUSION: We propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.

Incomplete devil's staircase in the magnetization curve of SrCu2(BO3)2.

We report on NMR and torque measurements on the frustrated quasi-two-dimensional spin-dimer system SrCu(2)(BO(3))(2) in magnetic fields up to 34 T that reveal a sequence of magnetization plateaus at 1/8, 2/15, 1/6, and 1/4 of the saturation and two incommensurate phases below and above the 1/6 plateau. The magnetic structures determined by NMR involve a stripe order of triplets in all plateaus, suggesting that the incommensurate phases originate from proliferation of domain walls. We propose that the magnetization process of SrCu(2)(BO(3))(2) is best described as an incomplete devil's staircase.

Magnetization of SrCu2(BO3)2 in ultrahigh magnetic fields up to 118 T.

The magnetization process of the orthogonal-dimer antiferromagnet SrCu2(BO3)2 is investigated in high magnetic fields of up to 118 T. A 1/2 plateau is clearly observed in the field range 84 to 108 T in addition to 1/8, 1/4, and 1/3 plateaus at lower fields. Using a combination of state-of-the-art numerical simulations, the main features of the high-field magnetization, a 1/2 plateau of width 24 T, a 1/3 plateau of width 34 T, and no 2/5 plateau, are shown to agree quantitatively with the Shastry-Sutherland model if the ratio of inter- to intradimer exchange interactions J'/J=0.63. It is further predicted that the intermediate phase between the 1/3 and 1/2 plateaus is not uniform but consists of a 1/3 supersolid followed by a 2/5 supersolid and possibly a domain-wall phase, with a reentrance into the 1/3 supersolid above the 1/2 plateau.

Infinite-layer iron oxide with a square-planar coordination.

Conventional high-temperature reactions limit the control of coordination polyhedra in transition-metal oxides to those obtainable within the bounds of known coordination geometries for a given transition metal. For example, iron atoms are almost exclusively coordinated by three-dimensional polyhedra such as tetrahedra and octahedra. However, recent works have shown that binary metal hydrides act as reducing agents at low temperatures, allowing access to unprecedented structures. Here we show the reaction of a perovskite SrFeO3 with CaH2 to yield SrFeO2, a new compound bearing a square-planar oxygen coordination around Fe2+. SrFeO2 is isostructural with 'infinite layer' cupric oxides, and exhibits a magnetic order far above room temperature in spite of the two-dimensional structure, indicating strong in-layer magnetic interactions due to strong Fe d to O p hybridization. Surprisingly, SrFeO2 remains free from the structural instability that might well be expected at low temperatures owing to twofold orbital degeneracy in the Fe2+ ground state with D(4h) point symmetry. The reduction and the oxidation between SrFeO2 and SrFeO3 proceed via the brownmillerite-type intermediate SrFeO2.5, and start at the relatively low temperature of approximately 400 K, making the material appealing for a variety of applications, including oxygen ion conduction, oxygen gas absorption and catalysis.

Unveiling new quantum phases in the Shastry-Sutherland compound SrCu2(BO3)2 up to the saturation magnetic field.

Under magnetic fields, quantum magnets often undergo exotic phase transitions with various kinds of order. The discovery of a sequence of fractional magnetization plateaus in the Shastry-Sutherland compound SrCu2(BO3)2 has played a central role in the high-field research on quantum materials, but so far this system could only be probed up to half the saturation value of the magnetization. Here, we report the first experimental and theoretical investigation of this compound up to the saturation magnetic field of 140 T and beyond. Using ultrasound and magnetostriction techniques combined with extensive tensor-network calculations (iPEPS), several spin-supersolid phases are revealed between the 1/2 plateau and saturation (1/1 plateau). Quite remarkably, the sound velocity of the 1/2 plateau exhibits a drastic decrease of -50%, related to the tetragonal-to-orthorhombic instability of the checkerboard-type magnon crystal. The unveiled nature of this paradigmatic quantum system is a new milestone for exploring exotic quantum states of matter emerging in extreme conditions.

Galanin-like peptide: a key player in the homeostatic regulation of feeding and energy metabolism?

The hypothalamus has a critical role in the regulation of feeding behavior, energy metabolism and reproduction. Galanin-like peptide (GALP), a novel 60 amino-acid peptide with a nonamidated C-terminus, was first discovered in porcine hypothalamus. GALP is mainly produced in the hypothalamic arcuate nucleus and is involved in the regulation of feeding behavior and energy metabolism, with GALP-containing neurons forming networks with several feeding-regulating peptide-containing neurons. The effects of GALP on food intake and body weight are complex. In rats, the central effect of GALP is to first stimulate and then reduce food intake, whereas in mice, GALP has an anorectic function. Furthermore, GALP regulates plasma luteinizing hormone levels through activation of gonadotropin-releasing hormone-producing neurons, suggesting that it is also involved in the reproductive system. This review summarizes the research on these topics and discusses current evidence regarding the function of GALP, particularly in relation to feeding and energy metabolism. We also discuss the effects of GALP activity on food intake, body weight and locomotor activity after intranasal infusion, a clinically viable mode of delivery.

Ferromagnetically coupled Shastry-Sutherland quantum spin singlets in (CuCl)LaNb2O7.

A thorough crystal structure determination at very low temperature of (CuCl)LaNb2O7, originally proposed as a spin-1/2 square-lattice antiferromagnet, is reported thanks to the use of single-crystal x-ray diffraction and powder neutron diffraction. State-of-the-art calculations (maximum entropy method) reveal that (CuCl)LaNb2O7 is orthorhombic with Pbam symmetry. First-principles calculations demonstrate that the dominant magnetic interactions are antiferromagnetic between fourth nearest neighbors with a Cu-Cl-Cl-Cu exchange path, which lead to the formation of spin singlets. The two strongest interactions between the singlets are ferromagnetic, which makes (CuCl)LaNb2O7 the first system of ferromagnetically coupled Shastry-Sutherland quantum spin singlets.

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma.

Retinoic acid (RA) has been shown to induce neuronal differentiation and/or apoptosis, and is widely used as a chemotherapeutic agent for treating the patients with neuroblastoma. However, the therapeutic effect of RA is still limited. To unveil the molecular mechanism(s) inducing differentiation and apoptosis in neuroblastoma cells, we compared CHP134 and NB-39-nu cell lines, in which all-trans-RA (ATRA) induces apoptosis, with LA-N-5 and RTBM1 cell lines, in which it induces neuronal differentiation. Here, we found that Bcl-2 was strongly downregulated in CHP134 and NB-39-nu cells, whereas it was abundantly expressed in LA-N-5 and RTBM1 cells. ATRA-mediated apoptosis in CHP134 and NB-39-nu cells was associated with a significant activation of caspase-9 and caspase-3 as well as cytoplasmic release of cytochrome c from mitochondria in a p53-independent manner. Enforced expression of Bcl-2 significantly inhibited ATRA-mediated apoptosis in CHP134 cells. In addition, treatment of RTBM1 cells with a Bcl-2 inhibitor, HA14-1, enhanced apoptotic response induced by ATRA. Of note, two out of 10 sporadic neuroblastomas expressed bcl-2 at undetectable levels and underwent cell death in response to ATRA in primary cultures. Thus, our present results suggest that overexpression of Bcl-2 is one of the key mechanisms to give neuroblastoma cells the resistance against ATRA-mediated apoptosis. This may provide a new therapeutic strategy against the ATRA-resistant and aggressive neuroblastomas by combining treatment with ATRA and a Bcl-2 inhibitor.

Isolation and characterization of a cDNA that encodes mouse fibroblast tropomyosin isoform 2.

We isolated and characterized a cDNA clone encoding tropomyosin isoform 2 (TM2) from a mouse fibroblast cDNA library. TM2 was found to contain 284 amino acids and was closely related to the rat smooth and skeletal muscle alpha-TMs and the human fibroblast TM3. The amino acid sequence of TM2 showed a nearly complete match with that of human fibroblast TM3 except for the region from amino acids 189 to 213, the sequence of which was identical to those of rat smooth and skeletal muscle alpha-TMs. These results suggest that TM2 is expressed from the same gene that encodes the smooth muscle alpha-TM, the skeletal muscle alpha-TM, and TM3 via an alternative RNA-splicing mechanism. Comparison of the expression of TM2 mRNA in low-metastatic Lewis lung carcinoma P29 cells and high-metastatic D6 cells revealed that it was significantly less in D6 cells than in P29 cells, supporting our previous observations (K. Takenaga, Y. Nakamura, and S. Sakiyama, Mol. Cell. Biol. 8:3934-3937, 1988) at the protein level.

Isolation of cDNA clones for mouse cytoskeletal gamma-actin and differential expression of cytoskeletal actin mRNAs in mouse cells.

We described the structures of mouse cytoskeletal gamma-actin cDNA clones and showed that there is strong conservation of the untranslated regions with human gamma-actin cDNA. In addition, we found that the expression levels of beta- and gamma-actin mRNAs are differentially controlled in various mouse tissues and cell types but are coordinately increased in the cellular growing state. These results suggest that there are multiple regulatory mechanisms of cytoskeletal actin genes and are consistent with the argument that beta- and gamma-actins might have functional diversity in mammalian cells.

Neuropeptide W is present in antral G cells of rat, mouse, and human stomach.

Neuropeptide W (NPW) is a 30-amino-acid peptide initially isolated from the porcine hypothalamus as an endogenous ligand for the G protein-coupled receptors GPR7 and GPR8. An intracerebroventricular administration of NPW increased serum prolactin and corticosterone concentrations, decreased dark-phase feeding, raised energy expenditure, and lowered body weight. Peripherally, GPR7 receptors are abundantly expressed throughout the gastrointestinal tract; the presence of NPW in the gastrointestinal endocrine system, however, remains unstudied. Using monoclonal and polyclonal antibodies raised against rat NPW, we studied the localization of NPW in the rat, mouse, and human stomach by light and electron microscopy. NPW-immunoreactive cells were identified within the gastric antral glands in all three species. Double immunohistochemistry and electron-microscopic immunohistochemistry studies in rats demonstrated that NPW is present in antral gastrin (G) cells. NPW immunoreactivity localized to round, intermediate-to-high-density granules in G cells. NPW-immunoreactive cells accounted for 90% chromagranin A- and 85% gastrin-immunoreactive endocrine cells in the rat gastric antral glands. Using reversed-phase HPLC coupled with enzyme immunoassays specific for NPW, we detected NPW30 and its C-terminally truncated form, NPW23, in the gastric mucosa. Plasma NPW concentration of the gastric antrum was significantly higher than that of the systemic vein, suggesting that circulating NPW is derived from the stomach. Plasma NPW concentration of the gastric antrum decreased significantly after 15-h fast and increased after refeeding. This is the first report to clarify the presence of NPW peptide in the stomachs of rats, mice, and humans. In conclusion, NPW is produced in gastric antral G cells; our findings will provide clues to additional mechanisms of the regulation of gastric function by this novel brain/gut peptide.

Galanin-like peptide promotes feeding behaviour via activation of orexinergic neurones in the rat lateral hypothalamus.

Galanin-like peptide (GALP) is produced in neurones in the hypothalamic arcuate nucleus and is implicated in the neural control of feeding behaviour. Previously, we have reported that GALP immunoreactive fibres were in direct contact with orexin/hypocretin immunoreactive neurones in the rat lateral hypothalamus using double-immunofluorescence. Centrally administered GALP is known to stimulate feeding behaviour. However, the target neurones of this action have not been clarified. The present study aimed to determine features of the GALP-mediated neuronal feeding pathway in rat. Accordingly, at the ultrastructural level, GALP-immunoreactive axon terminals were found to make synapses on orexin/hypocretin immunoreactive cell bodies and dendritic processes in the lateral hypothalamus. c-Fos immunoreactivity was expressed in orexin/hypocretin-immunoreactive neurones but not in melanin concentrating hormone-immunoreactive neurones in the lateral hypothalamus at 90 min after the application of GALP by i.c.v. infusion. Furthermore, to determine whether GALP regulates feeding behaviour via orexin/hypocretin neurones, the feeding behaviour of rats was studied following GALP i.c.v. injection with or without anti-orexin A and B immunoglobulin (IgG) pretreatment. The anti-orexin IgGs markedly inhibited GALP-induced hyperphagia. These results suggest that orexin/hypocretin-containing neurones in the lateral hypothalamus are targeted by GALP, and that GALP-induced hyperphagia is mediated via orexin/hypocretin neurones in the rat hypothalamus.

Isolation and characterization of a complementary DNA clone for a Mr 32,000 protein which is induced with tumor promoters in BALB/c 3T3 cells.

The synthesis of a protein of Mr 32,000 (p32) is enhanced by various tumor promoters, chemical carcinogens, metal salts, and heat shock in BALB/c 3T3 cells. We have isolated a complementary DNA (cDNA) clone for p32 from a lambda gt10 library of BALB/c 3T3 cells. The library was constructed from mRNA extracted from the cells treated with sodium arsenite, which stimulates the p32 expression most effectively among various agents so far tested. Having screened this library differentially with probes which represent induced and uninduced mRNA populations for p32, we first obtained a partial p32 cDNA clone and have subsequently succeeded in the isolation of a cDNA clone containing the entire coding sequence. RNA blot analysis has shown that p32 mRNA is induced as early as 0.5 h after the addition of 12-O-tetradecanoyl-phorbol-13-acetate or sodium arsenite. Computer-assisted comparison with GenBank data has revealed a striking similarity in the nucleotide sequences between cDNAs of p32 and rat heme oxygenase. These results strongly suggest that p32 is a mouse homolog of this enzyme.

[Metastatic lung tumor from uterine leiomyosarcoma].

We herein present 2 cases of metastatic lung tumor derived from uterine leiomyosarcoma. In the case 1, a 59-year-old woman was admitted to our hospital to examine abnormal shadow detected on chest X-ray. She had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 19 months previously. A round 3 cm mass in the right lung (S10) was seen on chest X-ray and computed tomography (CT). No other distant metastases or local recurrence were found, and the right lower lobectomy was perfomed under the clinical diagnosis of metastatic lung tumor. Postoperative pathologic examination revealed the tumor as a metastatic leiomyosarcoma. The patient recovered uneventfully, and there have been no signs of recurrence for 26 months after the pulmonary resection. In the case 2, a 58-year-old woman, who had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 7 months previously, was admitted to our hospital for further examination of pulmonary tumors on chest X-ray. Two tumors were recognized in the left lung (S8 and S10) on chest X-ray and CT. No other distant metastases or local recurrence were found, and the left lower lobectomy was performed under the clinical diagnosis of metastatic lung tumors. Pathological examinations revealed smooth muscle cells with nuclear pleomorphism and high mitotic indices. The tumors proved to be lung metastases derived from uterine leiomyosarcoma. Postoperative course was uneventful. However, brain metastasis was found 1 month after the pulmonary resection, and she underwent resection of brain metastasis. Two months after the brain metastasectomy, local recurrence of the brain tumor developed and re-resection followed by stereotactic radiotherapy was performed. Furthermore, intrapelvic recurrence was found 4 months after the pulmonary resection. Exploratory laparotomy revealed the tumor was unresectable, and she received 4 courses of chemotherapy (paclitaxel and carboplatin). For metastatic lung tumor from uterine leiomyosarcoma, surgery has been considered the best choice. However, for patients with uterine leiomyosarcoma who cannot be treated surgically because of multiple metastatic tumors or poor surgical risk chemotherapy (paclitaxel and carboplatin) or stereotactic radiotherapy can be strategies.

High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma.

Survivin (SVV) is a family member of inhibitor of apoptosis proteins (IAPs) and its expression is cell cycle regulated. The gene is mapped to chromosome 17q25, the region of which is frequently gained in advanced stages of neuroblastoma (NBL). However, the role of SVV in NBL is poorly understood. Here we studied the clinical and biological role of SVV in NBL. A 1.9 kb SVV transcript was expressed in all of 9 NBL cell lines at higher levels than those in adult cancer cell lines. In 34 primary NBLs, high levels of SVV expression was significantly associated with age greater than 12 months (two sample t-test: P= 0.0003), advanced stages (P = 0.0136), sporadic tumors (P= 0.0027) and low levels of TrkA expression (P = 0.0030). In NBL cell lines, SVV mRNA expression was dramatically down-regulated in CHP134 and IMR32 cells undergoing apoptosis after treatment with all-trans retinoic acid (RA) or serum deprivation. It was only moderately decreased in cells (SH-SY5Y and CHP901) undergoing RA-induced differentiation. On the other hand, in proliferating NBL cells or RA-treated SK-N-AS line which is refractory to RA, the SVV mRNA remained at steady state levels or rather up-regulated. Furthermore, transfection of SVV into CHP134 cells induced remarkable inhibition of the RA-induced apoptosis. Collectively, our results suggest that high expression of SVV is a strong prognostic indicator for the advanced stage neuroblastomas, and that it could be one of the candidate genes for the 17q gain.