Prediction of nitrogen metabolism-related genes in Anabaena by kernel-based network analysis

Prediction of molecular interaction networks from large-scale datasets in genomics and other omics experiments is an important task in terms of both developing bioinformatics methods and solving biological problems. We have applied a kernel-based network inference method for extracting functionally related genes to the response of nitrogen deprivation in cyanobacteria Anabaena sp. PCC 7120 integrating three heterogeneous datasets: microarray data, phylogenetic profiles, and gene orders on the chromosome. We obtained 1348 predicted genes that are somehow related to known genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. While this dataset contained previously known genes related to the nitrogen deprivation condition, it also contained additional genes. Thus, we attempted to select any relevant genes using the constraints of Pfam domains and NtcA-binding sites. We found candidates of nitrogen metabolism-related genes, which are depicted as extensions of existing KEGG pathways. The prediction of functional relationships between proteins rather than functions of individual proteins will thus assist the discovery from the large-scale datasets.     

Intra- and extra-familial adverse childhood experiences and a history of childhood psychosomatic disorders among Japanese university students

Many patients with somatoform disorders are frequently encountered in psychosomatic clinics as well as in primary care clinics. To assess such patients objectively, the concept of somatosensory amplification may be useful. Somatosensory amplification refers to the tendency to experience a somatic sensation as intense, noxious, and disturbing. It may have a role in a variety of medical conditions characterized by somatic symptoms that are disproportionate to demonstrable organ pathology. It may also explain some of the variability in somatic symptomatology found among different patients with the same serious medical disorder. It has been assessed with a self-report questionnaire, the Somatosensory Amplification Scale. This instrument was developed in a clinical setting in the U.S., and the reliability and validity of the Japanese and Turkish versions have been confirmed as well.     

A Soluble Form of LMIR5/CD300b Amplifies Lipopolysaccharide-Induced Lethal Inflammation in Sepsis

Leukocyte mono-Ig-like receptor 5 (LMIR5, also called CD300b) is an activating receptor expressed in myeloid cells. We have previously demonstrated that T cell Ig mucin 1 works as a ligand for LMIR5 in mouse ischemia/reperfusion injury of the kidneys. In this article, we show that LMIR5 is implicated in LPS-induced sepsis in mice. Notably, neutrophils constitutively released a soluble form of LMIR5 (sLMIR5) through proteolytic cleavage of surface LMIR5. Stimulation with TLR agonists augmented the release of sLMIR5. LPS administration or peritonitis induction increased serum levels of sLMIR5 in mice, which was substantially inhibited by neutrophil depletion. Thus, neutrophils were the main source of LPS-induced sLMIR5 in vivo. On the other hand, i.p. administration of LMIR5-Fc, a surrogate of sLMIR5, bound to resident macrophages (M) and stimulated transient inflammation in mice. Consistently, LMIR5-Fc induced in vitro cytokine production of peritoneal M via its unknown ligand. Interestingly, LMIR5 deficiency profoundly reduced systemic cytokine production and septic mortality in LPS-administered mice, although it did not affect in vitro cytokine production of LPS-stimulated peritoneal M. Importantly, the resistance of LMIR5-deficient mice to LPS- or peritonitis-induced septic death was decreased by LMIR5-Fc administration, implicating sLMIR5 in LPS responses in vivo. Collectively, neutrophil-derived sLMIR5 amplifies LPS-induced lethal inflammation.     

Relationship between periodontal status and intellectual function among community-dwelling elderly persons

doi: 10.1111/j.1741‐2358.2011.00483.x
Relationship between periodontal status and intellectual function among community‐dwelling elderly persons Objective: The aim of this study was to indicate the relationship between periodontal status and intellectual function in the elderly. Background: Periodontal status has been shown to be related to demographic, socioeconomic, and psychological status. Intellectual function is a significant indicator of health status. Nevertheless, the relationship between periodontal status and intellectual function has not been elucidated in detail among the elderly. Materials and Methods: A total of 152 community‐dwelling elderly persons, aged 70–74 years, were enrolled in the study. Periodontal status was evaluated using the WHO Community Periodontal Index of Treatment Needs (CPITN). Intellectual function was assessed by four neuropsychological tests: Raven’s Coloured Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 (VirPA) task, extracted from the Wechsler Memory Scale Revised Edition, and the Block Design subtest, extracted from the Wechsler Adult Intelligence Scales, Third Edition. Correlations between CPITN and each test were examined using Spearman rank correlation coefficients. The ordinal regression model was constructed with CPITN as the dependent variable and neuropsychological test as the principal independent variable to adjust for demographic factors, general health, lifestyle and oral health behaviour. Results: Significant correlations were found between the RCPM test, the VerPA task, the Visual Paired Associates 1 and CPITN. In the ordinal regression model, CPITN was significantly related to measures of RCPM after adjusting for demographic factors, general health status, lifestyle and oral health behaviour. Conclusion: Intellectual function is considered a significant indicator of periodontal status among community‐dwelling elderly persons.     

Human mast cell chymase cleaves pro-IL-18 and generates a novel and biologically active IL-18 fragment

Increased release of IL-18 in the skin causes atopic dermatitis (AD)-like skin lesions, suggesting a role of IL-18 in the pathogenesis of AD. Caspase-1 is a well-known activator of IL-18, but caspase-1 knockout mice still have biologically active IL-18. Normal human keratinocyte constitutively produces pro-IL-18, but it is unable to activate it, suggesting the existence of an alternative pathway for IL-18 in the skin. Dermal accumulation of mast cells is commonly observed in AD patients and in experimental mouse models of AD. Connective tissue mast cells contain high amounts of chymase and tryptase in their cytoplasmic granules. In the present study, we demonstrated that activation of IL-18 is a novel function of human mast cell chymase. Human mast cell chymase rapidly cleaves recombinant pro-IL-18 at 56-phenylalanine and produces a biologically active IL-18 fragment that is smaller than any other reported IL-18-derived species. The human mast cell chymase and the novel IL-18-derived active peptide may be novel therapeutic targets in AD- and IL-18-associated diseases.     

Extracellular lactate as a dynamic vasoactive signal in the rat retinal microvasculature

We tested the hypothesis that extracellular lactate regulates the function of pericyte-containing retinal microvessels. Although abluminally positioned pericytes appear to adjust capillary perfusion by contracting and relaxing, knowledge of the molecular signals that regulate the contractility of these mural cells is limited. Here, we focused on lactate because this metabolic product is in the retinal extracellular space under both physiological and pathophysiological conditions. In microvessels freshly isolated from the adult rat retina, we used perforated-patch pipettes to monitor ionic currents, fura-2 to measure calcium levels, and time-lapse photography to visualize changes in mural cell contractility and lumen diameter. During lactate exposure, pericyte calcium rose; these cells contracted, and lumens constricted. This contractile response appears to involve a cascade of events resulting in the inhibition of Na+/Ca2+ exchangers (NCXs), the decreased of which function causes pericyte calcium to increase and contraction to be triggered. On the basis of our observation that gap junction uncouplers minimized the lactate-induced rise in pericyte calcium, we propose that the NCXs inhibited by lactate are predominately located in the endothelium. Indicative of the importance of endothelial/pericyte gap junctions, uncouplers of these junctions switched the pericyte response to lactate from contraction to relaxation. In addition, we observed that hypoxia, which closes microvascular gap junctions, also switched lactate's effect from vasocontraction to vasorelaxation. Thus the response of pericyte-containing retinal microvessels to extracellular lactate is metabolically modulated. The ability of lactate to serve as a vasoconstrictor when energy supplies are ample and a vasodilator under hypoxic conditions may be an efficient mechanism to link capillary function with local metabolic need.     

Feeding with both β-carotene and supplemental α-tocopherol enhances type 1 helper T cell activity among splenocytes isolated from DO11.10 mice

beta-Carotene and/or supplemental alpha-tocopherol were fed to DO11.10 mice to investigate their effect on the immune function of naive splenocytes. A high secretion of interleukin-12 and interferon-gamma in response to the ex vivo primary antigen presentation occurred only when both were fed. This is consistent with the suppressed immunoglobulin E production under the similar condition described in our previous report.     

Nanoscale elongating control of the self‐assembled protein filament with the cysteine‐introduced building blocks

Self‐assembly of artificially designed proteins is extremely desirable for nanomaterials. Here we show a novel strategy for the creation of self‐assembling proteins, named “Nanolego.” Nanolego consists of “structural elements” of a structurally stable symmetrical homo‐oligomeric protein and “binding elements,” which are multiple heterointeraction proteins with relatively weak affinity. We have established two key technologies for Nanolego, a stabilization method and a method for terminating the self‐assembly process. The stabilization method is mediated by disulfide bonds between Cysteine‐residues incorporated into the binding elements, and the termination method uses “capping Nanolegos,” in which some of the binding elements in the Nanolego are absent for the self‐assembled ends. With these technologies, we successfully constructed timing‐controlled and size‐regulated filament‐shape complexes via Nanolego self‐assembly. The Nanolego concept and these technologies should pave the way for regulated nanoarchitecture using designed proteins.