Publisher Correction: A weak topological insulator state in quasi-one-dimensional bismuth iodide.

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A weak topological insulator state in quasi-one-dimensional bismuth iodide.

The major breakthroughs in understanding of topological materials over the past decade were all triggered by the discovery of the Z2-type topological insulator-a type of material that is insulating in its interior but allows electron flow on its surface. In three dimensions, a topological insulator is classified as either 'strong' or 'weak'1,2, and experimental confirmations of the strong topological insulator rapidly followed theoretical predictions3-5. By contrast, the weak topological insulator (WTI) has so far eluded experimental verification, because the topological surface states emerge only on particular side surfaces, which are typically undetectable in real three-dimensional crystals6-10. Here we provide experimental evidence for the WTI state in a bismuth iodide, ß-Bi4I4. Notably, the crystal has naturally cleavable top and side planes-stacked via van der Waals forces-which have long been desirable for the experimental realization of the WTI state11,12. As a definitive signature of this state, we find a quasi-one-dimensional Dirac topological surface state at the side surface (the (100) plane), while the top surface (the (001) plane) is topologically dark with an absence of topological surface states. We also find that a crystal transition from the ß-phase to the α-phase drives a topological phase transition from a nontrivial WTI to a normal insulator at roughly room temperature. The weak topological phase-viewed as quantum spin Hall insulators stacked three-dimensionally13,14-will lay a foundation for technology that benefits from highly directional, dense spin currents that are protected against backscattering.

Rapid weight gain during infancy and early childhood is related to higher anthropometric measurements in preadolescence.

BACKGROUND: This study examined the relationship between rapid weight gain during infancy and/or early childhood and anthropometric measurements [body mass index (BMI), percent body fat (%BF), waist circumference (WC) and waist-to-height ratio (WHtR)] in preadolescence by sex. METHODS: Subjects were fourth-grade school children (aged 9 to 10 years) from elementary schools in Ina-town, Japan, in 2010. Measurements of height, weight, %BF and WC were conducted for each subject. We obtained data on height and weight of subjects at birth, age 1.5 years and age 3 years from the Maternal and Child Health handbook. Rapid weight gain was defined as a change in weight-for-age standard deviation score greater than 0.67 from birth to age 1.5 years (infancy) or from age 1.5 to 3 years (early childhood). RESULTS: All anthropometric variables (BMI, %BF, WC and WHtR) at age 9 to 10 years were significantly higher in the rapid weight gain during both infancy and early childhood period group than in the no rapid weight gain group, regardless of sex. When compared with the no rapid weight gain group, rapid weight gain during early childhood period had significantly higher BMI and WC in boys and BMI, %BF and WC in girls. Compared with the no rapid weight gain group, the rapid weight gain during infancy group had a significantly higher WC in boys and significantly higher BMI and WC in girls. CONCLUSION: Rapid weight gain during both infancy and early childhood was related to higher anthropometric measurements, including WHtR, among Japanese preadolescents, regardless of sex. This study suggests that rapid weight gain during infancy and early childhood may be a risk factor for general/abdominal obesity later in life.

Influence of eating quickly and eating until full on anthropometric gains in girls: A population-based, longitudinal study.

BACKGROUND: In examining childhood overweight/obesity, there is a need to consider both eating quickly and eating until full. This longitudinal study investigated the influence of eating quickly and/or eating until full on anthropometric variables and becoming overweight/obese among Japanese schoolgirls. METHODS: Study participants were fourth-grade schoolgirls (aged 9 or 10 years) in Ina Town, Japan. Physical examinations and a questionnaire survey were performed at baseline (fourth grade) and after 3 years (seventh grade). Height, weight, and waist circumference were measured in the physical examinations, while the data on eating quickly and eating until full were collected in the questionnaire survey. Analysis of variance and analysis of covariance were used to compare the differences in each anthropometric variable between fourth and seventh grade among groups. RESULTS: Data on 425 non-overweight/obese schoolgirls in fourth grade were analyzed. Gains in anthropometric variables (body mass index, waist circumference, and waist-to-height ratio) from fourth to seventh grade were significantly larger in the "eating quickly and eating until full" group than in the "not eating quickly and not eating until full" group. In contrast, there were no significant differences in the gains between the "eating quickly or eating until full" group and the "not eating quickly and not eating until full" group. The proportion of overweight/obese girls in seventh grade was higher in the "eating quickly and eating until full" group than in the other groups. CONCLUSIONS: Eating quickly and eating until full had a substantial impact on excess gains in anthropometric variables among schoolgirls, suggesting that modifying these eating behaviors may help prevent non-overweight/obese girls from the excess gains. Accordingly, school health programs need to focus on not eating quickly and/or not eating until full to prevent overweight/obesity; it is necessary to emphasize "the risk of overweight/obesity associated with these eating behaviors" in schools.

Rapid weight gain during early childhood is associated with overweight in preadolescence: a longitudinal study in Japan.

BACKGROUND: The objective of this study was to examine the relationship between rapid weight gain during early childhood and overweight in preadolescence by sex. METHOD: Study subjects were 676 boys and 620 girls in fourth grade (aged 9 or 10 years) from elementary schools in Ina-town, Japan, during 2010-2012. Height and weight of subjects at birth, age 1.5 and 3 years, were collected from the Maternal and Child Health Handbook, while values at 9-10 years were measured. Rapid weight gain was defined as a change in weight-for-age standard deviation score greater than 0.67 from birth to age 1.5 years (0-1.5 years) or from age 1.5 to 3 years (1.5-3 years). RESULTS: After adjustment for confounding factors, compared with no rapid weight gain, rapid weight gain during 0-1.5 years and 1.5-3 years or rapid weight gain during 1.5-3 years but not during 0-1.5 years significantly increased the odds ratio (OR) for overweight at age 9-10 years in boys (OR, 6.21; 95% confidence interval [CI], 2.84-13.58 and OR, 3.31; 95% CI, 1.67-6.54, respectively) and girls (OR, 7.55; 95% CI, 2.99-19.07 and OR, 3.42; 95% CI, 1.38-8.49, respectively). CONCLUSION: The present study suggests that rapid weight gain during early childhood was associated with being overweight in preadolescence, regardless of sex.

Mutation in insulin receptor attenuates oxidative stress and apoptosis in pancreatic beta-cells induced by nutrition excess: reduced insulin signaling and ROS.

Type 2 diabetes results from the failure of beta-cells to adequately compensate for insulin resistance. Although the reduction of beta-cell mass is because of increased cell death and/or inadequate replication or neogenesis, the mechanism underlying beta-cell mass reduction is not fully understood. Here, we clarify the role of insulin signaling pathway in the beta-cell apoptosis using insulin resistant model mice. Wild-type mice and those carrying a mutation in the insulin receptor (mIR) were fed either regular chow or a high-fat diet for 6 weeks and subsequently investigated for beta-cell apoptosis, endoplasmic reticulum stress, and oxidative stress. Insulin tolerance tests revealed that mIR mice fed a high-fat diet (mIRHF) had higher insulin resistance. Beta-cell apoptosis was increased 2-fold in the wild-type mice fed a high-fat diet (wHF) compared with control mice, whereas beta-cell apoptosis in mIRHF mice did not increase compared with that in mIR mice. The expression of endoplasmic reticulum stress markers in isolated islets did not differ between the groups. Staining of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal in islets of wHF mice significantly increased, but the staining in mIRHF mice was not different from that in control group. Gene expression of the antioxidant enzyme MnSOD was significantly higher in mIRHF mice than those in the other 3 groups. A mutation in the insulin receptor attenuated the oxidative stress and apoptosis in beta-cells even though high caloric nutrient was loaded. Our results suggest that reduced insulin signaling protects beta-cells thorough decline of oxidative stress.

Atomic and electronic structure of ultrathin Bi(111) films grown on Bi2Te3(111) substrates: evidence for a strain-induced topological phase transition.

We studied the atomic and electronic structures of ultrathin Bi(111) films grown on Bi(2)Te(3) by means of angle-resolved photoemission, first-principles calculations, and low-energy electron diffraction. These Bi films were found to be strained due to the influence of the substrate. Accordingly, the band structure is affected and Bi undergoes a topological phase transition; it is shown that the Z(2) topological invariant in three dimensions switches from +1 (trivial) to -1 (nontrivial or topological). This was clearly confirmed from the change in the surface-state dispersion near the Fermi level. Our discovery offers a method to produce novel topological systems from simple materials.

Heavy chain variable (VH) region diversity generated by VH gene replacement in the progeny of a single precursor cell transformed with a temperature-sensitive mutant of Abelson murine leukemia virus.

Sequence analysis of a large number of DNA clones containing a functional heavy chain variable, diversity, and joining (VHDJH) complex generated by VH to VHDJH joining (VH gene replacement) in the progeny derived from a common precursor cell transformed with a temperature-sensitive (ts) Abelson murine leukemia virus (A-MuLV) indicates that endogenous VH gene replacement in vitro generates immunoglobulin gene joints distinct from those generated by the usual VH to DJH joining. Such joints keep the pentamer CAAGA at the 3' end of the donor VH segment and lack a recognizable D segment, as can be seen also in vivo. The results suggest that VH gene replacement participates in generating VH region diversity in vivo, as previously postulated. During the joining process, a unique VH gene was selected in all progeny cells, together with a single A nucleotide dominantly added to the junctional boundaries. The basis of these regulatory processes is discussed.

Fabrication of a novel magnetic topological heterostructure and temperature evolution of its massive Dirac cone.

Materials that possess nontrivial topology and magnetism is known to exhibit exotic quantum phenomena such as the quantum anomalous Hall effect. Here, we fabricate a novel magnetic topological heterostructure Mn4Bi2Te7/Bi2Te3 where multiple magnetic layers are inserted into the topmost quintuple layer of the original topological insulator Bi2Te3. A massive Dirac cone (DC) with a gap of 40-75 meV at 16 K is observed. By tracing the temperature evolution, this gap is shown to gradually decrease with increasing temperature and a blunt transition from a massive to a massless DC occurs around 200-250 K. Structural analysis shows that the samples also contain MnBi2Te4/Bi2Te3. Magnetic measurements show that there are two distinct Mn components in the system that corresponds to the two heterostructures; MnBi2Te4/Bi2Te3 is paramagnetic at 6 K while Mn4Bi2Te7/Bi2Te3 is ferromagnetic with a negative hysteresis (critical temperature  ~20 K). This novel heterostructure is potentially important for future device applications.

A mouse serine/threonine kinase homologous to C. elegans UNC51 functions in parallel fiber formation of cerebellar granule neurons.

The formation of the cerebellar circuitry depends on the outgrowth of connections between the two principal classes of neurons, granule neurons and Purkinje neurons. To identify genes that function in axon outgrowth, we have isolated a mouse homolog of C. elegans UNC51, which is required for axon formation, and tested its function in cerebellar granule neurons. Murine Unc51.1 encodes a novel serine/threonine kinase and is expressed in granule cells in the cerebellar cortex. Retroviral infection of immature granule cells with a dominant negative Unc51.1 results in inhibition of neurite outgrowth in vitro and in vivo. Moreover, infected neurons fail to express TAG-1 or neuron-specific beta-tubulin, suggesting that development is arrested prior to this initial step of differentiation. Thus, Unc51.1 signals the program of gene expression leading to the formation of granule cell axons.

Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta.

Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell adhesion. The protein strongly binds to hydroxyapatite and play an important role in calcification. Expression of osteopontin mRNA was analyzed in human aortic atherosclerotic lesion by Northern blot hybridization, as well as by in situ hybridization. The expression of osteopontin mRNA was detected in 24 out of 25 samples of aorta obtained from 17 autopsy cases, but not in one normal aortic sample. The magnitude of expression was proportional to the stage of atherosclerosis. In situ hybridization revealed that the cells expressing osteopontin mRNA were detected in the wall surrounding atheroma and closely associated with calcification. They were morphologically identified as foam cells and immunohistologically positive with HHF35, appearing to be derived from smooth muscle cells. These findings have suggested that smooth muscle cell-derived foam cells express osteopontin mRNA and play an important role in calcification of the atherosclerotic lesions.

The toxic conformation of the 42-residue amyloid beta peptide and its relevance to oxidative stress in Alzheimer's disease.

Senile plaques in the brain of patients with Alzheimer's disease mainly consist of aggregates of amyloid beta peptides (Abeta42, Abeta40). Abeta42 is more neurotoxic than Abeta40. This review describes recent findings from a structural analysis of Abeta42 aggregates and discusses their relevance to neurotoxicity through the formation of radicals.

Interface electronic structure at the topological insulator-ferrimagnetic insulator junction.

An interface electron state at the junction between a three-dimensional topological insulator film, Bi2Se3, and a ferrimagnetic insulator film, Y3Fe5O12 (YIG), was investigated by measurements of angle-resolved photoelectron spectroscopy and x-ray absorption magnetic circular dichroism. The surface state of the Bi2Se3 film was directly observed and localized 3d spin states of the Fe3+ in the YIG film were confirmed. The proximity effect is likely described in terms of the exchange interaction between the localized Fe 3d electrons in the YIG film and delocalized electrons of the surface and bulk states in the Bi2Se3 film.

Nerve injury induces the expression of EXT2, a glycosyltransferase required for heparan sulfate synthesis.

Heparan sulfate proteoglycans, which bear long chains of heparan sulfate glycosaminoglycan, play significant roles during embryogenesis, including the formation of the CNS. However, their involvement in nerve regeneration has not yet been clarified. Here, we found that the mRNA expression of EXT2, one of the crucial enzymes for heparan sulfate-glycosaminoglycan synthesis, was markedly up-regulated in injured hypoglossal motor neurons after axotomy. In addition, immunohistochemical staining with an antibody specific for heparan sulfate-glycosaminoglycan chains demonstrated increased expression of heparan sulfate-glycosaminoglycan chains in the injured nucleus. Furthermore, the mRNA expressions of glypican-1 and syndecan-1, which are both well-known heparan sulfate proteoglycans, were prominently up-regulated in injured motor neurons. These results suggest that the biosynthesis of heparan sulfate chains promoted by EXT2 is activated in injured motor neurons, and that glypican-1 and syndecan-1 are potent candidates for heparan sulfate proteoglycans involved in peripheral nerve regeneration.

Insulin resistance and increased pancreatic beta-cell proliferation in mice expressing a mutant insulin receptor (P1195L).

Several mutations of the tyrosine kinase domain of insulin receptor (IR) have been clinically reported to lead insulin resistance and insulin hypersecretion in humans. However, it has not been completely clarified how insulin resistance and pancreatic beta-cell function affect each other under the expression of mutant IR. We investigated the response of pancreatic beta-cells in mice carrying a mutation (P1195L) in the tyrosine kinase domain of IR beta-subunit. Homozygous (Ir(P1195L/P1195L)) mice showed severe ketoacidosis and died within 2 days after birth, and heterozygous (Ir(P1195L/wt)) mice showed normal levels of plasma glucose, but high levels of plasma insulin in the fasted state and after glucose loading, and a reduced response of plasma glucose lowering effect to exogenously administered insulin compared with wild type (Ir(wt/wt)) mice. There were no differences in the insulin receptor substrate (IRS)-2 expression and its phosphorylation levels in the liver between Ir(P1195L/wt) and Ir(wt/wt) mice, both before and after insulin injection. This result may indicate that IRS-2 signaling is not changed in Ir(P1195L/wt) mice. The beta-cell mass increased due to the increased numbers of beta-cells in Ir(P1195L/wt) mice. More proliferative beta-cells were observed in Ir(P1195L/wt) mice, but the number of apoptotic beta-cells was almost the same as that in Ir(wt/wt) mice, even after streptozotocin treatment. These data suggest that, in Ir(P1195L/wt) mice, normal levels of plasma glucose were maintained due to high levels of plasma insulin resulting from increased numbers of beta-cells, which in turn was due to increased beta-cell proliferation rather than decreased beta-cell apoptosis.

Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia.

BACKGROUND/OBJECTIVE: Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial. METHODS: We examined the antidiabetic effect of EPA in insulin receptor mutant (Insr(P1195L/+)) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia. RESULTS: EPA supplementation was found to alleviate hyperglycemia of Insr(P1195L/+) mice fed HFD (Insr(P1195L/+)/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in Insr(P1195L/+) mice but not in wild-type mice, suggesting that Insr(P1195L/+) mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of Insr(P1195L/+) mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia. CONCLUSIONS: EPA exerts an antidiabetic effect in Insr(P1195L/+)/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia.

Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains.

The UNC-51 serine/threonine kinase of C. elegans plays an essential role in axonal elongation, and unc-51 mutants exhibit uncoordinated movements. We have previously identified mouse and human cDNAs encoding UNC-51-like kinase (ULK1). Here we report the identification and characterization of the second murine member of this kinase family, ULK2. Mouse ULK2 cDNA encodes a putative polypeptide of 1033 aa which has an overall 52% and 33% amino acid identity to ULK1 and UNC-51, respectively. ULKs and UNC-51 share a typical domain structure of an amino-terminal kinase domain, a central proline/serine rich (PS) domain, and a carboxy-terminal (C) domain. Northern blot analysis showed that ULK2 mRNA is widely expressed in adult tissues. In situ hybridization analysis indicated that ULK2 mRNA is ubiquitously localized in premature as well as mature neurons in developing nervous system. ULK2 gene was mapped to mouse chromosome 11B1.3 and rat chromosome 10q23 by FISH. HA-tagged ULK2 expressed in COS7 cells had an apparent molecular size of approximately 150 kDa and was autophosphorylated in vitro. Truncation mutants suggested that the autophosphorylation occurs in the PS domain. Although expression of ULK2 failed to rescue unc-51 mutant of C. elegans, a series of ULK2/UNC-51 chimeric kinases revealed that function of the kinase and PS domains are conserved among species, while the C domain acts in a species-specific manner. These results suggest that ULK2 is involved in a previously uncharacterized signaling pathway in mammalian cells.

Isolation and characterization of genomic and cDNA clones encoding mouse senescence marker protein-30 (SMP30).

We isolated and characterized genomic and cDNA clones encoding mouse senescence marker protein-30 (SMP30), the protein amounts of which are known to decrease with aging in the livers of rats. This decrease in the expression of SMP30 is independent of androgen. SMP30 is a calcium binding protein also called regucalcin. The expression of SMP30 in aged mouse liver and 5' flanking sequence of the genome were also characterized. The cDNA contained an open reading frame encoding 299 amino acids with a calculated molecular weight of 33-404. The amino acid sequence of mouse SMP30 showed 94% similarity to rat SMP30 and 89% to human SMP30. Northern blot analysis specifically detected mouse SMP30 transcript in the liver and also confirmed its significant decrease with aging. Analysis of the murine genomic clone revealed that SMP30 was organized by seven exons and six introns, spanning approx. 17.5 kb. Primer extension analysis revealed that two major transcription initiation sites were localized at 101 bp and 102 bp upstream from ATG translation initiation codon. The nucleotide (nt) sequence of 5' flanking region showed a TATA-like sequence, a CAAT box, and SP-1 sites at nt -29, -72 and -169 in the promoter region, respectively. Interestingly, we found two classes of C/EBP sites which are highly and constantly expressed in the liver, in addition to AP-2, AP-1, GATA-1, AP-1/GRE and GAGA sites. These results provide important clues for understanding the regulatory mechanism of SMP30 gene expression and its relationship to aging.

Isolation of cDNA clone encoding rat senescence marker protein-30 (SMP30) and its tissue distribution.

We have isolated and characterized two cDNA clones encoding senescence marker protein-30 (SMP30), the amounts of which are known to decrease androgen-independently with aging in the livers of rats. Of these cDNA clones, one consisted of 1588 bp nucleotides and the other of 1195 bp nucleotides generated by alternative polyadenylation. These two cDNA clones shared the same open reading frame, but the larger species had 393 bp nucleotides of 3' untranslated region in addition to the first polyadenylation site of smaller species. Northern hybridization analysis showed that two species of mRNA (1.7 kb and 1.4 kb) located in the liver and kidney were consistent with these short and long forms of cDNA. The open reading frame, 897 bp could encode 299 amino acids. The estimated molecular weight and pI of the deduced polypeptide were 33,387 and 5.1, respectively. Furthermore, immunohistochemical analysis confirmed that SMP30 was preferentially localized in the hepatocytes and renal proximal tubular epithelium. Genomic Southern hybridization analysis demonstrated that SMP30 was widely conserved among higher animals. A computer-assisted homology analysis of nucleic acid and protein databases revealed no remarkable homology with other known proteins. Therefore, SMP30 seems to be a novel protein. In addition, the existence of putative A-U rich mRNA degradation signals and protein degradation signals (PEST sequence) in the structure of SMP30 may suggest important regulatory function of this unique protein manifested by changes in its concentrations.

Isolation of cDNA clone encoding human homologue of senescence marker protein-30 (SMP30) and its location on the X chromosome.

We have isolated and characterized a cDNA clone encoding human homologue of senescence marker protein-30 (SMP30), a calcium binding protein also called regucalcin (RC). This clone (pHSMP6) has 1356 base pairs (bp) and contains an open reading frame of 897 bp, which encodes 299 amino acids. The estimated molecular weight of the deduced polypeptide is 33,250 and pI is 5.836. The homology of amino acid sequences between human homologue and rat SMP30 is 88.6%. Using pHSMP6 as a probe, the chromosomal location of the human homologue of SMP30 gene was determined. The results of regional mapping using a panel of 11 rodent-human somatic hybrids indicated that the gene is located in the p11.3-q11.2 segment of the X chromosome. This gene thus could be a candidate for one of the X-linked diseases mapped to this regions.