Mutation accumulation under UV radiation in Escherichia coli

Mutations are induced by not only intrinsic factors such as inherent molecular errors but also by extrinsic mutagenic factors such as UV radiation. Therefore, identifying the mutational properties for both factors is necessary to achieve a comprehensive understanding of evolutionary processes both in nature and in artificial situations. Although there have been extensive studies on intrinsic factors, the mutational profiles of extrinsic factors are poorly understood on a genomic scale. Here, we explored the mutation profiles of UV radiation, a ubiquitous mutagen, in Escherichia coli on the genomic scale. We performed an evolution experiment under periodic UV radiation for 28 days. The accumulation speed of the mutations was found to increase so that it exceeded that of a typical mutator strain with deficient mismatch repair processes. The huge contribution of the extrinsic factors to all mutations consequently increased the risk of the destruction of inherent error correction systems. The spectrum of the UV-induced mutations was broader than that of the spontaneous mutations in the mutator. The broad spectrum and high upper limit of the frequency of occurrence suggested ubiquitous roles for UV radiation in accelerating the evolutionary process

Interferon-γ activates outwardly rectifying chloride channels in the human bronchial epithelial cell line BEAS-2B

The mechanism of increased chloride currents by inflammatory cytokine, interferon-gamma (IFN-γ), was investigated in cultured a human bronchial epithelial cell line (BEAS-2B) using cell-attached and inside-out patch configurations. The channel sensitive to chloride ion was activated by forskolin, an activator of adenylate cyclase, or 100μM dibutyryl 5'-cyclic monophosphate in cell-attached configurations. The conductance of this channel was 40±4 pS in symmetrical 150 mM chloride solution between membrane potentials of 0 to +50 mV, and this channel was blocked by 500μM 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS), suggesting that this channel was an outwardly rectifying chloride channel (ORCC). Treatment of 10-1000 U/ml IFN-γ for 3 hours, but not IFN-α, significantly increased channel activities of ORCC, and this activation was observed at least 24 hours after treatment. Erythromycin, a macrolide antibiotic, at a concentration of100μM inhibited the activation of ORCC induced by IFN-γ. The findings of the present study indicate that increased mucus secretion during inflammation might be partly due to activation of chloride permeability by cytokine and erythromycin might improve oversecretion of mucus from bronchial epithelium by blocking ORCC

Chlorido(12,17-dieth­oxy­carbonyl-11,18-dimethyl-2:3,6:7-dibutano­corrphycenato-κ4 N)iron(III)

The title complex, [Fe(C36H36N4O4)Cl], shows a domed structure with a slightly distorted trapezoidpyramidal core, in which the perpendicular displacements of the FeIII atom from the mean pyrrole N4 plane are 0.418 (3) and 0.465 (3) Å for the two crystallographically independent mol­ecules

Postural instability via a loss of intermittent control in elderly and patients with Parkinson's disease: a model-based and data-driven approach

Postural instability is one of the major symptoms of Parkinson's disease. Here, we assimilated a model of intermittent delay feedback control during quiet standing into postural sway data from healthy young and elderly individuals as well as patients with Parkinson's disease to elucidate the possible mechanisms of instability. Specifically, we estimated the joint probability distribution of a set of parameters in the model using the Bayesian parameter inference such that the model with the inferred parameters can best-fit sway data for each individual. It was expected that the parameter values for three populations would distribute differently in the parameter space depending on their balance capability. Because the intermittent control model is parameterized by a parameter associated with the degree of intermittency in the control, it can represent not only the intermittent model but also the traditional continuous control model with no intermittency. We showed that the inferred parameter values for the three groups of individuals are classified into two major groups in the parameter space: one represents the intermittent control mostly for healthy people and patients with mild postural symptoms and the other the continuous control mostly for some elderly and patients with severe postural symptoms. The results of this study may be interpreted by postulating that increased postural instability in most Parkinson's patients and some elderly persons might be characterized as a dynamical disease

CD40 and IFN-γ dependent T cell activation by human bronchial epithelial cells

We examined whether freshly isolated human bronchial cells (HBEC) and bronchial epithelial cell line/ BEAS-2B cells expressed surface molecules required for APC function. These cells expressed CD40 and ICAM-1, but not B7-1, B7-2 or HLA-DR molecules. Treatment of these cells with IFN-γ resulted in enhanced expression of CD40 and ICAM-1 as well as induction of HLA-DR expression. Th2 cytokines such as IL-4 and IL-5, proinflammatory cytokine of GM-CSF and nonspecific activator endotoxin had no effect on these phenotypic expressions. Functional examinations showed that allogeneic lymphocytes purified from peripheral blood strongly proliferated in response to BEAS-2B cells cultured with IFN-γ, but only weakly compared with those without IFN-γ. When allogeneic lymphocytes were purified to CD4+ cells, the proliferative response against BEAS-2B cells was abolished. Blockade of CD40-CD40L interaction by anti-CD40 antibody also inhibited the proliferation of lymphocytes to BEAS-2B cells, although this treatment showed a minimum effect on the response to allogeneic MNC. Thus, bronchial epithelial cells have the ability to present allogeneic antigens to T cells in both CD40- and IFN-γ- dependent manners under the presence of third party cells that transduce co-stimulatory signals

A case of sarcoidosis associated with chronic eosinophilic pneumonia

A 38-year-old man was hospitalized in our university hospital because of pulmonary opacities with bilateral hilar and mediastinal lymphadenopathy seen on chest radiograph. Eosinophilia was observed in the circulation and bronchoalveolar lavage (BAL) fluid. Histological examination revealed noncaseating epithelioid granulomas and eosinophilic infiltration in the lung. Based on these findings, a diagnosis of sarcoidosis combined with chronic eosinophilic pneumonia was made. The infiltrates on chest radiograph and BAL eosinophilia were promptly reduced with corticosteroid therapy, but only mild reduction was observed in diffuse nodular shadows and hilar and mediastinal lymphadenopathy, and high amounts of lymphocytes in BAL fluid remained. Increased IFN-γ, IL-4 and IL-5 were detected in the BAL fluid, and corticosteroid therapy reduced IL-4 and IL-5 (Th-2 cytokines) but not IFN-γ(Th-1 cytokine). These cytokine levels in BAL fluid were intimately correlated with the clinical course of sarcoidosis and chronic eosinophilic pneumonia

(12,17-Dieth­oxy­carbonyl-11,18-dimethyl-2,3:6,7-dibutano­corrphycenato)copper(II)–12,17-dieth­oxy­carbonyl-11,18-dimethyl-2:3,6:7-dibutano­corrphycene (3/97)

The corrphycene mol­ecule of the title compound, [Cu(C36H36N4O4)]0.034.0.966C36H38N4O4, has an essentially planar macrocyclic framwork with a slightly distorted trapezoidal N4 core; the r.m.s. deviation of the peripheral 20 C atoms and four N atoms is 0.054 (3) Å. The surface area within the N4-coordinating core (8.358 Å2) is significantly smaller than that (8.503 Å2) of the corresponding free-base porphyrin. Two intra­molecular N—H⋯N hydrogen bonds are observed. Detailed structure analysis clarified that the co-crystallization of the free-base corrphycene together with a quite minor component (ca 3%) of corrphycenato–CuII occurred in the recrystallization process

Synergistic effect of combining theophylline and drugs that potentially elevate serum creatine kinase

An increase in the serum creatine kinase (CK) level is one of the side effects of theophylline;on rare occasions, the increase may be followed by rhabdomyolysis. Theophylline is often administered with drugs that potentially elevate the serum CK level (CK-elevating drugs) such as β-agonists and steroids. However, the effects of the combined treatment of theophylline and CK-elevating drugs have not been reported. We, therefore, retrospectively investigated the effects of combined treatment on the serum CK level, in391asthmatic outpatients. In this study, the number and type of the CK-elevating drugs administered, and the serum levels of CK and theophylline, were investigated. The patients were divided into four groups:the theophylline-treated and CK-elevating drug-treated group, the theophylline-treated and non-CK-elevating drug-treated group, the non-theophylline-treated and CK-elevating drug-treated group, and the non-theophylline-treated and non-CK-elevating drug-treated group. The theophylline-treated and CK-elevating drug-treated group showed about 100%higher serum CK levels (225IU/L) than any other group (102-124IU/L), and no increase in the serum theophylline level. This result indicates that there is a synergistic effect of theophylline and CK-elevating drugs on the serum CK level. The combined treatment of theophylline and CK-elevating drugs induces a synergistic increase in the serum CK level, indicating not pharmacokinetic but pharmacodynamic interactions with these drugs

GaAs- MISFETs with insulating gate films formed by direct oxidation and by oxinitridation of recessed GaAs surfaces

金沢大学工学部Direct oxidation by an ultraviolet (UV) and ozone process and oxinitridation (plasma nitridation after oxidation) of GaAs surfaces were used to form nanometer-scale gate insulating layers for depletion-type recessed gate GaAs-MISFETs. The drain current-drain voltage characteristics of the oxide gate devices exhibit lower transconductance (max. 40 mS/mm), lower breakdown voltage and smaller gate capacitance than the oxinitrided gate devices. The presence of hysteresis in the oxide gate devices is also apparent. The maximum transconductance of the oxinitrided gate devices is 110 mS/mm and they have a sharper pinch-off, compared to the oxide gate devices. In addition, no hysteresis is observed in their current voltage curves. The current gain cutoff frequency of 1.4 μm gate-length FETs for both types is 6 GHz. These results correspond well with results obtained from characterization of these insulating films