Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

BACKGROUND: Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported. RESULTS: This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip(®). Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1) Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-κB. (2) Interferon (IFN)-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-α/β receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN. CONCLUSION: This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-α/β receptor-mediated paracrine pathway

Fabrication of a 64-Pixel TES Microcalorimeter Array with Iron Absorbers Uniquely Designed for 14.4-keV Solar Axion Search

If a hypothetical elementary particle called an axion exists, to solve the strong CP problem, a 57Fe nucleus in the solar core could emit a 14.4-keV monochromatic axion through the M1 transition. If such axions are once more transformed into photons by a 57Fe absorber, a transition edge sensor (TES) X-ray microcalorimeter should be able to detect them efficiently. We have designed and fabricated a dedicated 64-pixel TES array with iron absorbers for the solar axion search. In order to decrease the effect of iron magnetization on spectroscopic performance, the iron absorber is placed next to the TES while maintaining a certain distance. A gold thermal transfer strap connects them. We have accomplished the electroplating of gold straps with high thermal conductivity. The residual resistivity ratio (RRR) was over 23, more than eight times higher than a previous evaporated strap. In addition, we successfully electroplated pure-iron films of more than a few micrometers in thickness for absorbers and a fabricated 64-pixel TES calorimeter structure.Comment: 5 pages, 5 figures, published in IEEE Transactions on Applied Superconductivity on 8 March 202

Role of the node in controlling traffic of cadmium, zinc, and manganese in rice

Heavy metals are transported to rice grains via the phloem. In rice nodes, the diffuse vascular bundles (DVBs), which enclose the enlarged elliptical vascular bundles (EVBs), are connected to the panicle and have a morphological feature that facilitates xylem-to-phloem transfer. To find a mechanism for restricting cadmium (Cd) transport into grains, the distribution of Cd, zinc (Zn), manganese (Mn), and sulphur (S) around the vascular bundles in node I (the node beneath the panicle) of Oryza sativa ‘Koshihikari’ were compared 1 week after heading. Elemental maps of Cd, Zn, Mn, and S in the vascular bundles of node I were obtained by synchrotron micro-X-ray fluorescence spectrometry and electron probe microanalysis. In addition, Cd K-edge microfocused X-ray absorption near-edge structure analyses were used to identify the elements co-ordinated with Cd. Both Cd and S were mainly distributed in the xylem of the EVB and in the parenchyma cell bridge (PCB) surrounding the EVB. Zn accumulated in the PCB, and Mn accumulated around the protoxylem of the EVB. Cd was co-ordinated mainly with S in the xylem of the EVB, but with both S and O in the phloem of the EVB and in the PCB. The EVB in the node retarded horizontal transport of Cd toward the DVB. By contrast, Zn was first stored in the PCB and then efficiently transferred toward the DVB. Our results provide evidence that transport of Cd, Zn, and Mn is differentially controlled in rice nodes, where vascular bundles are functionally interconnected

Reliability and Validity of Speech Evaluation in Adductor Spasmodic Dysphonia

Objectives. In order to establish a reliable diagnostic tool for adductor spasmodic dysphonia (ADSD), it is necessary to determine the proper terms representing its characteristic voice symptoms and to relate them to objective measures such as acoustic parameters or speech perturbation. The aim of this study was to evaluate speech in patients with ADSD by perceptual evaluations and acoustic measures, and to examine the reliability and validity of the measures by comparison with normal controls. Methods. Twenty-four patients with ADSD and 24 healthy volunteers matched to the ADSD patients with regard to age and sex participated in the study. Speech materials, consisting of three short sentences, were constructed from serial voiced syllables to elicit abductor voice breaks. Three otolaryngologists specializing in phoniatrics rated the degree of voice symptoms using a visual analog scale (VAS). VAS sheets with five 100-mm horizontal lines were given to each rater. The ends of the lines were labeled normal versus severe, and the five lines were labeled as overall severity and each of the four voice symptoms; strangulation, interruption, tremor and strained speech. Nine words were selected from the speech materials for acoustic analysis, and abnormal acoustic events were classified into one of the three categories; percentage of frequency shifts, percentage of aperiodic segments, or percentage of phonation breaks. Acoustic measures were performed by a speech-language-hearing therapist specializing in voice disorders and five healthy university students. To evaluate the intra- and inter-rater/measurer reliability of the VAS scores or acoustic measures, Pearson r correlations were calculated. To examine the validity of perceptual evaluations and acoustic measures, the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Results. Pearson r correlation coefficients for overall severity showed the highest intra- and inter-rater reliability, and reliability coefficients for one of the four voice symptoms, strangulation (r = 0.816-0.937), were slightly higher than those for the other symptoms. For acoustic events, intra-measurer reliabilities were r = 0.645 (frequency shifts), r = 0.969 (aperiodic segments), and r = 1.0 (phonation breaks), and inter-measurer reliability ranged from r = 0.102 to r = 1.0 (average r = 0.861). The Pearson r correlation coefficient for phonation breaks was higher than those for the other acoustic events. Perceptual evaluation using VAS showed high sensitivity (91.7 %) and specificity (100 %), and acoustic analysis showed low sensitivity (70.8 %) and high specificity (100 %). Eight of the 24 patients were judged to be within normal limits by one or both evaluation methods. Conclusions. Both perceptual evaluation and acoustic measures alone were found to be likely to miss true ADSD patients. It is important to obtain a range of speech materials and to use a combination of perceptual evaluation and acoustic measures based on our understanding of the advantages and disadvantages of both methods

Axonal Pruning Is Actively Regulated by the Microtubule-Destabilizing Protein Kinesin Superfamily Protein 2A

Extensive axonal pruning and neuronal cell death are critical events for the development of the nervous system. Like neuronal cell death, axonal elimination occurs in discrete steps; however, the regulators of these processes remain mostly elusive. Here, we identify the kinesin superfamily protein 2A (KIF2A) as a key executor of microtubule disassembly and axonal breakdown during axonal pruning. Knockdown of Kif2a, but not other microtubule depolymerization or severing proteins, protects axonal microtubules from disassembly upon trophic deprivation. We further confirmed and extended this result to demonstrate that the entire degeneration process is delayed in neurons from the Kif2a knockout mice. Finally, we show that the Kif2a-null mice exhibit normal sensory axon patterning early during development, but abnormal target hyperinnervation later on, as they compete for limited skin-derived trophic support. Overall, these findings reveal a central regulatory mechanism of axonal pruning during development