Protective effects of FK506 against glutamate-induced neurotoxicity in retinal cell culture

Nanomoles of neuropeptide Y (NPY) and noradrenaline (NA), administered i.v. to pentobarbital-anesthetized rats, caused nearly equipotent dose-dependent pressor responses in normotensive rats. However, in renovascular Goldblatt hypertensive rats, the dose-response curves for both NPY and NA were significantly displaced to the left, approximately threefold. Intravenous administration of BIBP 3226 (30-180 microg/kg) did not consistently lower blood pressure, per se, but did evoke competitive antagonism of the NPY pressor response in both rat populations. The magnitude of the NPY antagonism evoked by BIBP 3226 was comparable in normotensive and hypertensive rats. The absence of NA antagonism demonstrates the selectivity of the BIBP 3226 blockade.     

Printed circuit heat exchanger thermal–hydraulic performance in supercritical CO2 experimental loop

Heat transfer and pressure drop characteristics of the Printed Circuit Heat Exchanger (PCHE) were investigated in an experimental supercritical CO₂ loop. The inlet temperature and pressure were varied from 280 to 300 °C/2.2 to 3.2 MPa in the hot side and from 90 to 108 °C/6.5 to 10.5 MPa in the cold side while the mass flow rate was varied from 40 to 80 kg h⁻¹. The overall heat transfer coefficient range is 300–650 W m⁻² K⁻¹ while the compactness with respect to the heat exchanger core is approximately 1050 m² m⁻³. The empirical correlations to predict the local heat transfer coefficient and pressure drop factor as a function of the Reynolds number have been proposed for the tested PCHE.     

Molecular characterization of the glutathione-dependent formaldehyde dehydrogenase gene FLD1 from the methylotrophic yeast Pichia methanolica

In this paper, we describe molecular characterization of the FLD1 gene, which encodes glutathione-dependent formaldehyde dehydrogenase (FLD), from the methylotrophic yeast Pichia methanolica. The P. methanolica FLD1 gene contains two exons corresponding to a gene product of 380 amino acid residues and a 225 bp intron, respectively, and its deduced amino acid sequence shows high similarity to those of Fld1ps from other methylotrophic yeasts (80-88%). In P. methanolica, FLD activity is mainly induced by methanol, and this induction is not completely repressed by glucose. Moreover, the expression of the PmFLD1 is strictly regulated, mainly at the mRNA level, its expression increasing with increasing methanol concentrations in the medium. These results suggest that FLD1 is involved in the detoxification of formaldehyde in methanol metabolism, and Fld1p coordinates the formaldehyde level in methanol-grown cells according to the methanol concentration on growth.     

Physiological role of the second alcohol oxidase gene MOD2 in the methylotrophic growth of Pichia methanolica

The methylotrophic yeast Pichia methanolica has nine multiple alcohol oxidase (AOD) isozymes, which can be detected on native electrophoretic polyacrylamide gel and are encoded by two genes, MOD1 and MOD2. The aim of this work is to reveal the physiological roles of these AOD subunits, especially that of Mod2p, encoded by the second AOD-encoding gene, MOD2. A strain expressing only MOD2 showed severe growth inhibition with a low concentration of methanol (0.1%), but its growth was restored with an increase in the methanol concentration (up to 3%). The expression of MOD2 using the CbAOD1 promoter in the Candida boidinii alcohol oxidase-depleted strain was more advantageous for methylotrophic growth with high methanol concentrations than that of MOD1. The expression of MOD2 was not observed under derepression conditions (0% methanol), and the expression level increased with an increase in the methanol concentration used for induction. The expression of MOD1 was observed under derepression conditions and was rather constant throughout the tested methanol concentration range. Therefore, the ratio of Mod2p to Mod1p in an active AOD octamer was proved to be mainly controlled by changes in the MOD2 mRNA level. These and other results show that Mod2p is a unique AOD subunit more adapted to methylotrophic growth with high methanol concentrations (3%) than Mod1p.     

Preparation and properties of LiTaO3-based solid solutions with cation vacancies

It has been found that nonstoichiometric solid solutions $\text{(}\text{Li}{}_{\mathrm{<mtext>1?</mtext><mtext>x</mtext>}}\text{M}{}^{\mathrm{2+}}{}_{\mathrm{<mtext>x</mtext><mtext>2</mtext>}}\text{□}{}_{\mathrm{<mtext>x</mtext><mtext>2</mtext>}}\text{)}\text{TaO}\text{3}$ with M=Zn, Ni, Mg and Ca exist over wide ranges. In the case of the Zn-system, especially, a LiTaO₃ structure was still stable even at x=0.5, where 25% of the Li sites are vacant. A new series of solid solutions shows ferroelectric properties. The Curie temperature is closely related with the axial ratio c/a of the hexagonal cell.     

Optimum design of agitator geometry for a dry stirred media mill by the discrete element method

Three different agitator geometries for a dry stirred media mill with a horizontal drum were studied experimentally and by DEM (discrete element method) simulation. Two optimized models, model A with stirring arms oriented in the same direction and model B with inclined stirring arms, achieved more rapid grinding with the lower adhesion of particles to the mill than the conventional stirring arms. Model A achieved the finest grinding with sharpest particle distribution.DEM simulation results suggested that rapid mixing, large collision energy, and a large number of collisions result in rapid grinding. DEM simulations of model A confirmed that the particle collision energy in this model was the highest of the models tested and resulted in the largest energy consumption and the largest temperature increase. In model B, DEM simulation results suggested that collision energy increased locally at the wall and resulted in a local temperature increase at the shaft. The high number of collisions in model B also resulted in rapid grinding but with a broad particle distribution. The decrease of the particle adhesion in models A and B was caused by a decrease in the collision energy between particles and the wall in the normal direction.     

Translating Multi-Agent Autoepistemic Logic into Logic Program

In order to develop a proof procedure of multi-agent autoepistemic Logic (MAEL), a natural framework to formalize belief and reasoning including inheritance, persistence, and causality, we introduce a method that translates a MAEL theory into a logic program with integrity constraints. It is proved that there exists one-to-one correspondence between extensions of a MAEL theory and stable models of a logic program translated from it. Our approach has the following advantages: (1) We can obtain all extensions of a MAEL theory if we compute all stable models of the translated logic program. (2) We can fully use efficient techniques or systems for computing stable models of a logic program. We also investigate the properties of reasoning in MAEL through this translation. The fact that the extension computing problem can be reduced to the stable model computing problem implies that there are close relationships between MAEL and other formalizations of nonmonotonic reasoning.     

SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Fas^lpr/lpr mice. Clinical and immunological phenotypes were compared between Fas^lpr/lpr and SH3BP2-deficient Fas^lpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220⁺CD4⁻CD8⁻ T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.     

DCTN1 Binds to TDP-43 and Regulates TDP-43 Aggregation

A common pathological hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis, is cytoplasmic mislocalization and aggregation of nuclear RNA-binding protein TDP-43. Perry disease, which displays inherited atypical parkinsonism, is a type of TDP-43 proteinopathy. The causative gene DCTN1 encodes the largest subunit of the dynactin complex. Dynactin associates with the microtubule-based motor cytoplasmic dynein and is required for dynein-mediated long-distance retrograde transport. Perry disease-linked missense mutations (e.g., p.G71A) reside within the CAP-Gly domain and impair the microtubule-binding abilities of DCTN1. However, molecular mechanisms by which such DCTN1 mutations cause TDP-43 proteinopathy remain unclear. We found that DCTN1 bound to TDP-43. Biochemical analysis using a panel of truncated mutants revealed that the DCTN1 CAP-Gly-basic supradomain, dynactin domain, and C-terminal region interacted with TDP-43, preferentially through its C-terminal region. Remarkably, the p.G71A mutation affected the TDP-43-interacting ability of DCTN1. Overexpression of DCTN1^G71A, the dynactin-domain fragment, or C-terminal fragment, but not the CAP-Gly-basic fragment, induced cytoplasmic mislocalization and aggregation of TDP-43, suggesting functional modularity among TDP-43-interacting domains of DCTN1. We thus identified DCTN1 as a new player in TDP-43 cytoplasmic-nuclear transport, and showed that dysregulation of DCTN1-TDP-43 interactions triggers mislocalization and aggregation of TDP-43, thus providing insights into the pathological mechanisms of Perry disease and other TDP-43 proteinopathies.