Showing papers by "University of Tsukuba published in 2009"

Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women: A Meta-analysis

Abstract: Context Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants. Objective To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women. Data Sources and Study Selection A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included. Data Extraction Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF ( Data Synthesis Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P Conclusions Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with a MAC of less 7.9 METs.

Ultralong spin coherence time in isotopically engineered diamond

Abstract: As quantum mechanics ventures into the world of applications and engineering, materials science faces the necessity to design matter to quantum grade purity. For such materials, quantum effects define their physical behaviour and open completely new (quantum) perspectives for applications. Carbon-based materials are particularly good examples, highlighted by the fascinating quantum properties of, for example, nanotubes or graphene. Here, we demonstrate the synthesis and application of ultrapure isotopically controlled single-crystal chemical vapour deposition (CVD) diamond with a remarkably low concentration of paramagnetic impurities. The content of nuclear spins associated with the (13)C isotope was depleted to 0.3% and the concentration of other paramagnetic defects was measured to be <10(13) cm(-3). Being placed in such a spin-free lattice, single electron spins show the longest room-temperature spin dephasing times ever observed in solid-state systems (T2=1.8 ms). This benchmark will potentially allow observation of coherent coupling between spins separated by a few tens of nanometres, making it a versatile material for room-temperature quantum information processing devices. We also show that single electron spins in the same isotopically engineered CVD diamond can be used to detect external magnetic fields with a sensitivity reaching 4 nT Hz(-1/2) and subnanometre spatial resolution.

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

Abstract: To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.

The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

Abstract: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Regulation of Gonadotropin-Releasing Hormone Secretion by Kisspeptin/Dynorphin/Neurokinin B Neurons in the Arcuate Nucleus of the Mouse

Abstract: Kisspeptin is encoded by the Kiss1 gene, and kisspeptin signaling plays a critical role in reproduction. In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide tonic drive to gonadotropin-releasing hormone (GnRH) neurons, which in turn supports basal luteinizing hormone (LH) secretion. Our objectives were to determine whether preprodynorphin (Dyn) and neurokinin B (NKB) are coexpressed in Kiss1 neurons in the mouse and to evaluate its physiological significance. Using in situ hybridization, we found that Kiss1 neurons in the Arc of female mice not only express the Dyn and NKB genes but also the NKB receptor gene (NK3) and the Dyn receptor [the kappa opioid receptor (KOR)] gene. We also found that expression of the Dyn, NKB, KOR, and NK3 in the Arc are inhibited by estradiol, as has been established for Kiss1, and confirmed that Dyn and NKB inhibit LH secretion. Moreover, using Dyn and KOR knock-out mice, we found that long-term disruption of Dyn/KOR signaling compromises the rise of LH after ovariectomy. We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence.

The Effects of Prosocial Video Games on Prosocial Behaviors: International Evidence From Correlational, Longitudinal, and Experimental Studies:

Abstract: Although dozens of studies have documented a relationship between violent video games and aggressive behaviors, very little attention has been paid to potential effects of prosocial games. Theoretically, games in which game characters help and support each other in nonviolent ways should increase both short-term and long-term prosocial behaviors. We report three studies conducted in three countries with three age groups to test this hypothesis. In the correlational study, Singaporean middle-school students who played more prosocial games behaved more prosocially. In the two longitudinal samples of Japanese children and adolescents, prosocial game play predicted later increases in prosocial behavior. In the experimental study, U.S. undergraduates randomly assigned to play prosocial games behaved more prosocially toward another student. These similar results across different methodologies, ages, and cultures provide robust evidence of a prosocial game content effect, and they provide support for the General Learning Model.

The Antioxidant Defense System Keap1-Nrf2 Comprises a Multiple Sensing Mechanism for Responding to a Wide Range of Chemical Compounds

Abstract: Animals have evolved defense systems for surviving in a chemically diverse environment. Such systems should demonstrate plasticity, such as adaptive immunity, enabling a response to even unknown chemicals. The antioxidant transcription factor Nrf2 is activated in response to various electrophiles and induces cytoprotective enzymes that detoxify them. We report here the discovery of a multiple sensing mechanism for Nrf2 activation using zebrafish and 11 Nrf2-activating compounds. First, we showed that six of the compounds tested specifically target Cys-151 in Keap1, the ubiquitin ligase for Nrf2, while two compounds target Cys-273. Second, in addition to Nrf2 and Keap1, a third factor was deemed necessary for responding to three of the compounds. Finally, we isolated a zebrafish mutant defective in its response to seven compounds but not in response to the remaining four. These results led us to categorize Nrf2 activators into six classes and hypothesize that multiple sensing allows enhanced plasticity in the system.

Loss of function of a proline-containing protein confers durable disease resistance in rice.

Abstract: Blast disease is a devastating fungal disease of rice, one of the world's staple foods. Race-specific resistance to blast disease has usually not been durable. Here, we report the cloning of a previously unknown type of gene that confers non-race-specific resistance and its successful use in breeding. Pi21 encodes a proline-rich protein that includes a putative heavy metal-binding domain and putative protein-protein interaction motifs. Wild-type Pi21 appears to slow the plant's defense responses, which may support optimization of defense mechanisms. Deletions in its proline-rich motif inhibit this slowing. Pi21 is separable from a closely linked gene conferring poor flavor. The resistant pi21 allele, which is found in some strains of japonica rice, could improve blast resistance of rice worldwide.

TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN.

Abstract: Akt kinase is activated by transforming growth factor-beta1 (TGF-beta) in diabetic kidneys, and has important roles in fibrosis, hypertrophy and cell survival in glomerular mesangial cells However, the mechanisms of Akt activation by TGF-beta are not fully understood Here we show that TGF-beta activates Akt in glomerular mesangial cells by inducing the microRNAs (miRNAs) miR-216a and miR-217, both of which target PTEN (phosphatase and tensin homologue), an inhibitor of Akt activation These miRNAs are located within the second intron of a non-coding RNA (RP23-298H61-001) The RP23 promoter was activated by TGF-beta and miR-192 through E-box-regulated mechanisms, as shown previously Akt activation by these miRs led to glomerular mesangial cell survival and hypertrophy, which were similar to the effects of activation by TGF-beta These studies reveal a mechanism of Akt activation through PTEN downregulation by two miRs, which are regulated by upstream miR-192 and TGF-beta Due to the diversity of PTEN function, this miR-amplifying circuit may have key roles, not only in kidney disorders, but also in other diseases

Pressure evolution of the low-temperature crystal structure and bonding of the superconductor FeSe (Tc =37 K)

Abstract: $\ensuremath{\alpha}\text{-FeSe}$ with the PbO structure is a key member of the family of high-${T}_{c}$ iron pnictide and chalcogenide superconductors, as while it possesses the basic layered structural motif of edge-sharing distorted ${\text{FeSe}}_{4}$ tetrahedra, it lacks interleaved ion spacers or charge-reservoir layers. We find that the application of hydrostatic pressure first rapidly increases ${T}_{c}$ which attains a broad maximum of 37 K at $\ensuremath{\sim}7\text{ }\text{GPa}$ before decreasing to 6 K upon further compression to $\ensuremath{\sim}14\text{ }\text{GPa}$. Complementary synchrotron x-ray diffraction at 16 K was used to measure the low-temperature isothermal compressibility of $\ensuremath{\alpha}\text{-FeSe}$, revealing an extremely soft solid with a bulk modulus, ${K}_{0}=30.7(1.1)\text{ }\text{GPa}$ and strong bonding anisotropy between interlayer and intralayer directions that transforms to the more densely packed $\ensuremath{\beta}$ polymorph above $\ensuremath{\sim}9\text{ }\text{GPa}$. The nonmonotonic ${T}_{c}(P)$ behavior of FeSe coincides with drastic anomalies in the pressure evolution of the interlayer spacing, pointing to the key role of this structural feature in modulating the electronic properties.

Indium tin oxide nanoparticles with compositionally tunable surface plasmon resonance frequencies in the near-IR region.

Abstract: Here we report the synthesis of conducting indium tin oxide (ITO) nanoparticles (NPs) and their surface plasmon resonance (SPR) properties. The SPR peaks of the ITO NPs can be easily tuned by changing the concentration of Sn doping from 3 to 30 mol %. The shortest SPR wavelength of 1618 nm in 10% Sn-doped ITO NPs may reflect the highest electron carrier density in the ITO NPs. The controllable SPR frequencies of metal oxides may offer a novel approach for noble-metal-free SPR applications. Unlike noble-metal nanostructures, ITO has no inter- and intraband transitions in the vis−near-IR region and represents a free-electron conduction, allowing us to systematically study the origin of optical effects arising from the SPRs of conduction electrons.

Prevalence of chronic kidney disease in the Japanese general population

Abstract: We previously estimated the prevalence of chronic kidney disease (CKD) stages 3–5 at 19.1 million based on data from the Japanese annual health check program for 2000–2004 using the Modification of Diet in Renal Disease (MDRD) equation multiplied by the coefficient 0.881 for the Japanese population. However, this equation underestimates the GFR, particularly for glomerular filtration rates (GFRs) of over 60 ml/min/1.73 m2. We did not classify the participants as CKD stages 1 and 2 because we did not obtain proteinuria data for all of the participants. We re-estimated the prevalence of CKD by measuring proteinuria using a dipstick test and by calculating the GFR using a new equation that estimates GFR based on data from the Japanese annual health check program in 2005. Data were obtained for 574,024 (male 240,594, female 333,430) participants over 20 years old taken from the general adult population, who were from 11 different prefectures in Japan (Hokkaido, Yamagata, Fukushima, Tochigi, Ibaraki, Tokyo, Kanazawa, Osaka, Fukuoka, Miyazaki and Okinawa) and took part in the annual health check program in 2005. The glomerular filtration rate (GFR) of each participant was computed from the serum creatinine value using a new equation: GFR (ml/min/1.73 m2) = 194 × Age−0.287 × S-Cr−1.094 (if female × 0.739). The CKD population nationwide was calculated using census data from 2005. We also recalculated the prevalence of CKD in Japan assuming that the age composition of the population was same as that in the USA. The prevalence of CKD stages 1, 2, 3, and 4 + 5 were 0.6, 1.7, 10.4 and 0.2% in the study population, which resulted in predictions of 0.6, 1.7, 10.7 and 0.2 million patients, respectively, nationwide. The prevalence of low GFR was significantly higher in the hypertensive and proteinuric populations than it was in the populations without proteinuria or hypertension. The prevalence rate of CKD in Japan was similar to that in the USA when the Japanese general population was age adjusted to the US 2005 population estimate. About 13% of the Japanese adult population—approximately 13.3 million people—were predicted to have CKD in 2005.

Association Between Serum Uric Acid and Development of Type 2 Diabetes

Abstract: OBJECTIVE To systematically evaluate the association between serum uric acid (SUA) level and subsequent development of type 2 diabetes. RESEARCH DESIGN AND METHODS We searched Medline (31 March from 1966 to 2009) and Embase (31 March from 1980 to 2009) for observational cohort studies examining the association between SUA and the risk of type 2 diabetes by manual literature search. Relative risks (RRs) for each 1 mg/dl increase in SUA were pooled by using a random-effects model. The studies included were stratified into subgroups representing different study characteristics, and meta-regression analyses were performed to investigate the effect of these characteristics on the association between SUA level and type 2 diabetes risk. RESULTS The search yielded 11 cohort studies (42,834 participants) that reported 3,305 incident cases of type 2 diabetes during follow-up periods ranging from 2.0 to 13.5 years. The pooled RR of a 1 mg/dl increase in SUA was 1.17 (95% CI 1.09–1.25). Study results were consistently significant (i.e., >1) across characteristics of participants and study design. Publication bias was both visually and statistically suggested (P = 0.03 for Egger9s test, 0.06). Adjustment for publication bias attenuated the pooled RR per mg/dl increase in SUA (RR 1.11 [95% CI 1.03–1.20]), but the association remained statistically significant (P = 0.009). CONCLUSIONS The current meta-analysis suggests that SUA level is positively associated with the development of type 2 diabetes regardless of various study characteristics. Further research should attempt to determine whether it is effective to utilize SUA level as a predictor of type 2 diabetes for its primary prevention.

2+1 Flavor Lattice QCD toward the Physical Point

Abstract: We present the first results of the PACS-CS project which aims to simulate $2+1$ flavor lattice QCD on the physical point with the nonperturbatively $O(a)$-improved Wilson quark action and the Iwasaki gauge action. Numerical simulations are carried out at $\ensuremath{\beta}=1.9$, corresponding to the lattice spacing of $a=0.0907(13)\text{ }\text{ }\mathrm{fm}$, on a ${32}^{3}\ifmmode\times\else\texttimes\fi{}64$ lattice with the use of the domain-decomposed HMC algorithm to reduce the up-down quark mass. Further algorithmic improvements make possible the simulation whose up-down quark mass is as light as the physical value. The resulting pseudoscalar meson masses range from 702 MeV down to 156 MeV, which clearly exhibit the presence of chiral logarithms. An analysis of the pseudoscalar meson sector with SU(3) chiral perturbation theory reveals that the next-to-leading order corrections are large at the physical strange quark mass. In order to estimate the physical up-down quark mass, we employ the SU(2) chiral analysis expanding the strange quark contributions analytically around the physical strange quark mass. The SU(2) low energy constants ${\overline{l}}_{3}$ and ${\overline{l}}_{4}$ are comparable with the recent estimates by other lattice QCD calculations. We determine the physical point together with the lattice spacing employing ${m}_{\ensuremath{\pi}}$, ${m}_{K}$ and ${m}_{\ensuremath{\Omega}}$ as input. The hadron spectrum extrapolated to the physical point shows an agreement with the experimental values at a few % level of statistical errors, albeit there remain possible cutoff effects. We also find that our results of ${f}_{\ensuremath{\pi}}$, ${f}_{K}$ and their ratio, where renormalization is carries out perturbatively at one loop, are compatible with the experimental values. For the physical quark masses we obtain ${m}_{ud}^{\overline{\mathrm{MS}}}$ and ${m}_{s}^{\overline{\mathrm{MS}}}$ extracted from the axial-vector Ward-Takahashi identity with the perturbative renormalization factors. We also briefly discuss the results for the static quark potential.

Listeria monocytogenes ActA-mediated escape from autophagic recognition

Abstract: Autophagy degrades unnecessary organelles and misfolded protein aggregates, as well as cytoplasm-invading bacteria. Nevertheless, the bacteria Listeria monocytogenes efficiently escapes autophagy. We show here that recruitment of the Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial surface disguises the bacteria from autophagic recognition, an activity that is independent of the ability to mediate bacterial motility. L. monocytogenes expressing ActA mutants that lack the ability to recruit the host proteins initially underwent ubiquitylation, followed by recruitment of p62 (also known as SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to mediate protection from ubiquitylation was further demonstrated by generating aggregate-prone GFP-ActA-Q79C and GFP-ActA-170(*) chimaeras, consisting of GFP (green fluorescent protein), the ActA protein and segments of polyQ or Golgi membrane protein GCP170 (ref. 6). GFP-ActA-Q79C and GFP-ActA-170(*) formed aggregates in the host cell cytoplasm, however, these ActA-containing aggregates were not targeted for association with ubiquitin and p62. Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy.

Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.

Abstract: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.

Nrf2 Enhances Cell Proliferation and Resistance to Anticancer Drugs in Human Lung Cancer

Abstract: Purpose: NF-E2-related factor 2 (Nrf2), a key transcription regulator for antioxidant and detoxification enzymes, is abundantly expressed in cancer cells. In this study, therefore, the role of Nrf2 in cancer cell proliferation and resistance to anticancer drugs was investigated. Experimental Design: We used three human lung cancer cell lines with different degrees of Nrf2 activation: Nrf2 was highly activated in A549 cells, slightly activated in NCI-H292 cells, and not activated in LC-AI cells under unstimulated conditions. Result: A549 cells showed higher resistance to cisplatin compared with NCI-H292 and LC-AI cells. The resistance to cisplatin was significantly inhibited in A549 but not in NCI-H292 or LC-AI cells by knockdown of Nrf2 with its specific small interfering RNA (Nrf2-siRNA). The cell proliferation was also most prominently inhibited in A549 cells by treatment with Nrf2-siRNA. In A549 cells, the expression of self-defense genes, such as antioxidant enzymes, phase II detoxifying enzymes, and drug efflux pumps, was significantly reduced by Nrf2-siRNA concomitant with a reduction of the cellular glutathione level. The degree of DNA crosslink and apoptosis after treatment with cisplatin was significantly elevated in A549 cells by Nrf2-siRNA. Knockdown of Nrf2 arrested the cell cycle at G 1 phase with a reduction of the phosphorylated form of retinoblastoma protein in A549 and NCI-H292 cells but not in LC-AI cells. Conclusion: These results indicate that the Nrf2 system is essential for both cancer cell proliferation and resistance to anticancer drugs. Thus, Nrf2 might be a potential target to enhance the effect of anticancer drugs.

Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses

Abstract: Toll-like receptor (TLR) signals perform a crucial role in innate immune responses to pathogens. In this study, we found that the aryl hydrocarbon receptor (Ahr) negatively regulates inflammatory responses mediated by lipopolysaccharide (LPS) in macrophages. Ahr was induced in macrophages stimulated by LPS, but not by transforming growth factor (TGF)-β plus interleukin (IL)-6, which can induce Ahr in naive T cells. The production of IL-6 and tumor necrosis factor (TNF)-α by LPS was significantly elevated in Ahr-deficient macrophages compared with that in wild-type (WT) cells. Ahr-deficient mice were more highly sensitive to LPS-induced lethal shock than WT mice. Signal transducer and activator of transcription 1 (Stat1) deficiency, as well as Ahr deficiency, augmented LPS-induced IL-6 production. We found that Ahr forms a complex with Stat1 and nuclear factor-kappa B (NF-κB) in macrophages stimulated by LPS, which leads to inhibition of the promoter activity of IL-6. Ahr thus plays an essential role in the negative regulation of the LPS signaling pathway through interaction with Stat1.

NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo

Abstract: NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell-mediated innate immunity to melanoma cells and provide a background to design NK cell-based immunotherapeutic strategies against melanoma and possibly other tumors.

Map-Based Cloning of the Gene Associated With the Soybean Maturity Locus E3

Abstract: Photosensitivity plays an essential role in the response of plants to their changing environments throughout their life cycle. In soybean [Glycine max (L.) Merrill], several associations between photosensitivity and maturity loci are known, but only limited information at the molecular level is available. The FT3 locus is one of the quantitative trait loci (QTL) for flowering time that corresponds to the maturity locus E3. To identify the gene responsible for this QTL, a map-based cloning strategy was undertaken. One phytochrome A gene (GmPhyA3) was considered a strong candidate for the FT3 locus. Allelism tests and gene sequence comparisons showed that alleles of Misuzudaizu (FT3/FT3; JP28856) and Harosoy (E3/E3; PI548573) were identical. The GmPhyA3 alleles of Moshidou Gong 503 (ft3/ft3; JP27603) and L62-667 (e3/e3; PI547716) showed weak or complete loss of function, respectively. High red/far-red (R/FR) long-day conditions enhanced the effects of the E3/FT3 alleles in various genetic backgrounds. Moreover, a mutant line harboring the nonfunctional GmPhyA3 flowered earlier than the original Bay (E3/E3; PI553043) under similar conditions. These results suggest that the variation in phytochrome A may contribute to the complex systems of soybean flowering response and geographic adaptation.

Coordination of PGC-1β and iron uptake in mitochondrial biogenesis and osteoclast activation

Abstract: Bone is resorbed by osteoclasts, and too much activity by these cells leads to disease, such as osteoporosis. Here Kyoji Ikeda and colleagues show that the combined action of iron uptake and a key transcription factor involved in mitochondrial biogenesis are required for the proper functioning of these cells and that in cases of increased bone loss, iron chelation may be beneficial by inhibiting these cells.

Substitution Effects on FeSe Superconductor

Abstract: We have investigated the effect of atomic substitutions in the FeSe system, which exhibits the simplest crystal structure among the iron-based superconductors. An enhancement of the superconducting transition temperature T c was observed with the substitution of S or Te for Se; the T c increased with S substitution by up to 20%, and also increased with Te substitution up to 75%. In contrast, Co or Ni substitutions for the Fe site significantly suppressed superconductivity. In this work we present a detailed description of the substitution technique employed to determine T c in the FeSe system.

Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells

Abstract: Olive oil intake has been shown to induce significant levels of apoptosis in various cancer cells. These anti-cancer properties are thought to be mediated by phenolic compounds present in olive. These beneficial health effects of olive have been attributed, at least in part, to the presence of oleuropein and hydroxytyrosol. In this study, oleuropein and hydroxytyrosol, major phenolic compound of olive oil, was studied for its effects on growth in MCF-7 human breast cancer cells using assays for proliferation (MTT assay), cell viability (Guava ViaCount assay), cell apoptosis, cellcycle (flow cytometry). Oleuropein or hydroxytyrosol decreased cell viability, inhibited cell proliferation, and induced cell apoptosis in MCF-7 cells. Result of MTT assay showed that 200 μg/mL of oleuropein or 50 μg/mL of hydroxytyrosol remarkably reduced cell viability of MCF-7 cells. Oleuropein or hydroxytyrosol decrease of the number of MCF-7 cells by inhibiting the rate of cell proliferation and inducing cell apoptosis. Also hydroxytyrosol and oleuropein exhibited statistically significant block of G1 to S phase transition manifested by the increase of cell number in G0/G1 phase.

Acute Effects of Aerobic Exercise on Cognitive Function in Older Adults

Abstract: The present study investigated the effects of acute aerobic exercise on cognitive brain functions of older adults. Twenty-four males (12 older and 12 younger adults) performed a modified flanker task during a baseline session (no exercise) and after light and moderate cycling exercise in counterbalanced order on different days while measures of task performance and the P3 component of an event-related brain potential were collected. The results indicated that, for both age groups, reaction time following moderate exercise was shorter relative to the other sessions, and P3 latencies following both light and moderate exercise were shorter compared with the baseline session. In contrast, P3 amplitude increased only following moderate exercise in younger adults. These findings suggest that light and moderate exercises improve cognitive function across the adult lifespan, although the mechanisms underlying the effects of observed acute aerobic exercise on cognitive function may be age dependent.