高効率線形送信法におけるPWM包絡線発生法の研究

電気通信大学200

Leukocyte CCR2 expression is associated with mini-mental state examination score in older adults

This is a copy of an article published in Rejuvenation Research © 2012 Mary Ann Liebert, Inc.; Rejuvenation Research is available online at: http://online.liebertpub.com.Circulating inflammatory markers may play an important role in cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif) receptor 2 (CCR2) develop an accelerated Alzheimer-like pathology. CCR2 is also important in neurogenesis. To identify human gene transcripts most closely associated with Mini-Mental State Examination (MMSE) scores, we undertook a genome-wide and inflammation specific transcriptome screen in circulating leukocytes from a population-based sample

Experimental and theoretical electron density analysis of copper pyrazine nitrate quasi-low-dimensional quantum magnets

The accurate electron density distribution and magnetic properties of two metal-organic polymeric magnets, the quasi-one-dimensional (1D) Cu(pyz)(NO3)2 and the quasi-two-dimensional (2D) [Cu(pyz)2(NO3)]NO3·H2O, have been investigated by high-resolution single-crystal X-ray diffraction and Density Functional Theory calculations on the whole periodic systems and on selected fragments. Topological analyses, based on Quantum Theory of Atoms in Molecules, enabled the characterization of possible magnetic exchange pathways and the establishment of relationships between the electron (charge and spin) densities and the exchange-coupling constants. In both compounds, the experimentally observed anti-ferromagnetic coupling can be quantitatively explained by the Cu-Cu super-exchange pathway mediated by the pyrazine bridging ligands, via a σ-type interaction. From topological analyses of experimental charge-density data, we show for the first time that the pyrazine tilt angle does not play a role in determining the strength of the magnetic interaction. Taken in combination with molecular orbital analysis and spin density calculations, we find a synergistic relationship between spin delocalization and spin polarization mechanisms and that both determine the bulk magnetic behavior of these Cu(II)-pyz coordination polymers

Inhibitors of Streptococcus pneumoniae Surface Endonuclease EndA Discovered by High-Throughput Screening Using a PicoGreen Fluorescence Assay

The human commensal pathogen, Streptococcus pneumoniae, expresses a number of virulence factors that promote serious pneumococcal diseases, resulting in significant morbidity and mortality worldwide. These virulence factors may give S. pneumoniae the capacity to escape immune defenses, resist antimicrobial agents, or a combination of both. Virulence factors also present possible points of therapeutic intervention. The activities of the surface endonuclease, EndA, allow S. pneumoniae to establish invasive pneumococcal infection. EndA’s role in DNA uptake during transformation contributes to gene transfer and genetic diversitifcation. Moreover, EndA’s nuclease activity degrades the DNA backbone of neutrophil extracellular traps (NETs), allowing pneumococcus to escape host immune responses. Given its potential impact on pneumococcal pathogenicity, EndA is an attractive target for novel antimicrobial therapy. Herein, we describe the development of a high-throughput screening assay for the discovery of nuclease inhibitors. Nuclease-mediated digestion of double-stranded DNA was assessed using fluorescence intensity changes of the DNA dye ligand, PicoGreen. Under optimized conditions, the assay provided robust and reproducible activity data (Z'=0.87) and was used to screen 4727 small molecules against an imidazole-rescued variant of EndA. In total, 10 small molecules were confirmed as novel EndA inhibitors that may have utility as research tools for understanding pneumococcal pathogenesis, and ultimately drug discovery

Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Background: Lower muscle strength in midlife predicts disability and mortality in later life. Bloodborne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Methods: Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n=7,781, ages: 20-104 years, weighted mean=56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, male/female). Results: Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation and the stress response. Ten genes were only associated in younger individuals, four in males only and one in females only. For example PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (=60 years). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts Conclusions: This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age and sex specific gene expression signatures in blood for muscle strength.Wellcome TrustFHS gene expression profiling was funded through the Division of Intramural Research (Principal Investigator, Daniel Levy), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Dr. Murabito is supported by NIH grant R01AG029451. Dr. Kiel is supported by NIH R01 AR41398. The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute contract N01-HC-25195.The InCHIANTI study was supported in part by the Intramural Research Program, National Institute on Aging, NIH, Baltimore MD USA. D.M. and L.W.H. were generously supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). W.E.H. was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health in EnglandThe infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos Institute).The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93- 28 015; RIDE2), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of RNA-expression array data for the Rotterdam Study was executed and funded by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Marjolein Peters, MSc, Ms. Mila Jhamai, Ms. Jeannette M. Vergeer-Drop, Ms. Bernadette van Ast-Copier, Mr. Marijn Verkerk and Jeroen van Rooij, BSc for their help in creating the RNA array expression databaseSHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Caché Campus program of the InterSystems GmbH

Enhancing easy-plane anisotropy in bespoke Ni(II) quantum magnets

We examine the crystal structures and magnetic properties of several S = 1 Ni(II) coordination compounds, molecules and polymers, that include the bridging ligands HF2-, AF62- (A = Ti, Zr) and pyrazine or non-bridging ligands F-, SiF62-, glycine, H2O, 1-vinylimidazole, 4-methylpyrazole and 3-hydroxypyridine. Pseudo-octahedral NiN4F2, NiN4O2 or NiN4OF cores consist of equatorial Ni-N bonds that are equal to or slightly longer than the axial Ni-Lax bonds. By design, the zero-field splitting (D) is large in these systems and, in the presence of substantial exchange interactions (J), can be difficult to discriminate from magnetometry measurements on powder samples. Thus, we relied on pulsed-field magnetization in those cases and employed electron-spin resonance (ESR) to confirm D when J 0) and range from ≈ 8-25 K. This work reveals a linear correlation between the ratio d(Ni-Lax)/d(Ni-Neq) and D although the ligand spectrochemical properties may also be important. We assert that this relationship allows us to predict the type of magnetocrystalline anisotropy in tailored Ni(II) quantum magnets

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Long-term Site Fidelity and Individual Home Range Shifts in Lophocebus albigena

We investigated long-term site fidelity of gray-cheeked mangabey (Lophocebus albigena) groups in Kibale National Park, Uganda. Concurrently, we monitored shifts in home range by individual females and subadult and adult males. We documented home range stability by calculating the area of overlap in successive years, and by recording the drift of each group’s monthly centroid from its initial location. Home ranges remained stable for 3 of our 4 groups (overlap over 10 yr >60%). Core areas were more labile, but group centroids drifted an average of only 530 m over the entire decade. Deviations from site fidelity were associated with dispersal or group fission. During natal dispersal, subadult males expanded their home ranges over many months, settling ≤4 home ranges away. Adult males, in contrast, typically dispersed within a few days to an adjacent group in an area of home range overlap. Adult males made solitary forays, but nearly always into areas used by their current group or by a group to which they had previously belonged. After secondary dispersal, they expanded their ranging in the company of their new group, apparently without prior solitary exploration of the new area. Some females also participated in home range shifts. Females shifted home ranges only within social groups, in association with temporary or permanent group splits. Our observations raise the possibility that male mangabeys use a finder-joiner mechanism when moving into new home ranges during secondary dispersal. Similarly, females might learn new resource locations from male immigrants before or during group fission