Cohesive properties of PbBi/Fe3O4 and PbBi/(Fe,Cr)3O4 interfaces.

First principles calculations reveal that the effects of PbBi on the cohesive properties of Fe3O4 and (Fe,Cr)3O4: PbBi can reduce the cohesive strength of the oxides, and the contents of O and Cr on the O-terminated oxide side play a significant role in the cohesive properties of the PbBi/Fe3O4 and PbBi/(Fe,Cr)3O4 interfaces. Specifically, the performance of oxidation decreases more significantly under the conditions of insufficient oxygen, and a high ratio of Cr of the subsurface of oxides can lead to the reduction of the cohesive properties of O-terminated interfaces. Calculations also show that the Pb-O-terminated interfaces are energetically favorable and are more stable than the Bi-O-terminated surfaces due to the strong bond of Pb-O, while the Bi-Cr and Bi-Fe interfaces are more stable than the Pb-Cr and Pb-Fe interfaces. Moreover, it is found that the stability and cohesion of the PbBi/Fe3O4 and PbBi/(Fe,Cr)3O4 interfaces will decrease when the oxygen concentration is insufficient or the degree of wetting of PbBi of oxides is low, and the PbBi/Fe3O4 interface is more sensitive to these conditions. The bond-dissociation energies and electronic structures provide a deep understanding of various interface properties, and the obtained results are in good agreement with experimental measurements in the literature.

Heats of formation and stress-strain relationship of Fe-Cr solid solutions from a constructed Fe-Cr potential.

A new Fe-Cr interatomic potential is constructed under the framework of the embedded-atom method and has better performances in predicting heats of formation and stress-strain relationship of Fe-Cr solid solutions than the Fe-Cr potentials already published in the literature. Based on the constructed Fe-Cr potential, molecular dynamics simulation reveals that the heats of formation of BCC Fe-Cr solid solutions at 1600 K are positive within the entire composition range, and the calculated values are in good agreement with corresponding experimental measurements in the literature. In addition, it is also found that the tensile strengths of BCC Fe-Cr solid solutions increase with the increase of the Cr composition, and that BCC Fe-Cr solid solutions are less ductile with smaller critical strains than both Fe and Cr. The simulated results are discussed and compared with the corresponding experimental and calculated evidence in the literature to validate the relevance of the newly constructed Fe-Cr potential.

Effects of trigonal deformation on electronic structure and thermoelectric properties of bismuth.

First principles calculation and Boltzmann transport theory have been used to reveal the effects of trigonal deformation on electronic structure and thermoelectric properties of bulk bismuth. It is found that the semimetal-semiconductor transition would happen at the critical c/a points of 2.41 and 2.51, and that such a transition should be ascribed to the opposite changes of band edges at T and L points during trigonal deformation. Calculations also reveal that trigonal deformation has an important effect on various temperature-dependent thermoelectric properties, and that carrier density plays a decisive role in determining the magnitude of Seebeck coefficient and figure of merit. The semimetal → semiconductor transition as a result of trigonal compression with the decrease of c/a fundamentally induces the best performance of the thermoelectric properties of bismuth at the c/a ratio of 2.45. The present results agree well with experimental observations in the literature, and provide a deep understanding of the intrinsic relationship between trigonal deformation, band structure, and thermoelectric properties of bismuth.

MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting.

The differentiation deficiencies of osteoclast precursors (pre-OCs) may contribute to osteoporosis. Research on osteoporosis has recently focused on microRNAs (miRNAs) that play crucial roles in pre-OC differentiation. In the current study, we aimed to analyze the expression and function of the glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation. We found that dexamethasone induced osteoclast differentiation and inhibited miR-338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor cells attenuated GC-induced osteoclast formation and bone resorption, whereas inhibition of miR-338-3p reversed these effects. The expression of the nuclear factor κB ligand RANKL, a potential target gene of miR-338-3p, was inversely correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone resorption. Taken together, these findings demonstrate that miR-338-3p may play a significant role in GC-induced osteoclast differentiation and function by targeting RANKL in osteoclasts.

Transcriptional profiling reveals global defects in energy metabolism, lipoprotein, and bile acid synthesis and transport with reversal by leptin treatment in ob/ob mouse liver.

Leptin, a hormone secreted by adipose tissue, has been shown to have a major influence on hepatic lipid and lipoprotein metabolism. To characterize changes in lipid and lipoprotein gene expression in mouse liver, suppression subtractive hybridization and cDNA microarray analysis were used to identify mRNAs differentially expressed after leptin treatment of ob/ob mice. Ob/ob mice showed a profound decrease in mRNAs encoding genes controlling bile acid synthesis and transport as well as a variety of apolipoprotein genes and hepatic lipase with reversal upon leptin administration, suggesting that leptin coordinately regulates high density lipoprotein and bile salt metabolism. Leptin administration also resulted in decreased expression of genes involved in fatty acid and cholesterol synthesis, glycolysis, gluconeogenesis, and urea synthesis, and increased expression of genes mediating fatty acid oxidation, ATP synthesis, and oxidant defenses. The changes in mRNA expression are consistent with a switch in energy metabolism from glucose utilization and fatty acid synthesis to fatty acid oxidation and increased respiration. The latter changes may produce oxidant stress, explaining the unexpected finding that leptin induces a battery of genes involved in antioxidant defenses. Expression cluster analysis revealed responses of several sets of genes that were kinetically linked. Thus, the mRNA levels of genes involved in fatty acid and cholesterol synthesis are rapidly (<1 h) repressed by leptin administration, in association with an acute decrease in plasma insulin levels and decreased sterol regulator element-binding protein-1 expression. In contrast, genes participating in fatty acid oxidation and ketogenesis were induced more slowly (24 h), following an increase in expression of their common regulatory factor, peroxisome proliferator-activated receptor alpha. However, the regulation of genes involved in high density lipoprotein and bile salt metabolism shows complex kinetics and is likely to be mediated by novel transcription factors.

Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model.

Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF/Ei x B6.129S7-Ldlr(tm1Her)) x C57BL/6J-Ldlr(tm1Her) backcross mice, homozygous for the Ldlr null allele, were fed a Western-type diet for 3 months and then killed for quantification of aortic lesions. A genome scan was carried out by using DNA pools and microsatellite markers spaced at approximately 18-centimorgan intervals. Quantitative trait locus analysis of individual backcross mice confirmed linkages to chromosomes 4 (Athsq1, logarithm of odds = 6.2) and 6 (Athsq2, logarithm of odds = 6.7). Athsq1 affected lesions in females only whereas Athsq2 affected both sexes. Among females, the loci accounted for approximately 50% of the total variance of lesion area. The susceptible allele at Athsq1 was derived from the MOLF/Ei genome whereas the susceptible allele at Athsq2 was derived from C57BL/6J. Inheritance of susceptible alleles at both loci conferred a 2-fold difference in lesion area, suggesting an additive effect of Athsq1 and Athsq2. No associations were observed between the quantitative trait loci and levels of plasma total cholesterol, high density lipoprotein cholesterol, non-high density lipoprotein cholesterol, insulin, or body weight. We provide strong evidence for complex inheritance of atherosclerosis in mice with elevated plasma low density lipoprotein cholesterol and show a major influence of nonlipoprotein-related factors on disease susceptibility. Athsq1 and Athsq2 represent candidate susceptibility loci for human atherosclerosis, most likely residing on chromosomes 1p36--32 and 12p13--12, respectively.

The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor.

The human cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high density lipoproteins to triglyceride-rich lipoproteins, indirectly facilitating cholesteryl esters uptake by the liver. Hepatic CETP gene expression is increased in response to dietary hypercholesterolemia, an effect that is mediated by the activity of liver X receptor/retinoid X receptor (LXR/RXR) on a direct repeat 4 element in the CETP promoter. In this study we show that the orphan nuclear receptor LRH-1 also transactivates the CETP promoter by binding to a proximal promoter element distinct from the DR4 site. LRH-1 potentiates the sterol-dependent regulation of the wild type CETP promoter by LXR/RXR. Small heterodimer partner, a repressor of LRH-1, abolishes the potentiation effect of LRH-1 but not its basal transactivation of the CETP promoter. Since this mode of regulation of CETP is very similar to that recently reported for the bile salt-mediated repression of Cyp7a (encoding the rate-limiting enzyme for conversion of cholesterol into bile acid in the liver), we examined the effects of bile salt feeding on CETP mRNA expression in human CETP transgenic mice. Hepatic CETP mRNA expression was repressed by a diet containing 1% cholic acid in male mice but was induced by the same diet in female mice. Microarray analysis of hepatic mRNA showed that about 1.5% of genes were repressed, and 2.5% were induced by the bile acid diet. However, the sexually dimorphic regulatory pattern of the CETP gene was an unusual response. Our data provide further evidence for the regulation of CETP and Cyp7a genes by similar molecular mechanisms, consistent with coordinate transcriptional regulation of sequential steps of reverse cholesterol transport. However, differential effects of the bile salt diet indicate additional complexity in the response of these two genes.

Decreased selective uptake of high density lipoprotein cholesteryl esters in apolipoprotein E knock-out mice.

Scavenger receptor BI (SR-BI) mediates the selective uptake of high density lipoprotein (HDL) cholesteryl esters (CE) by cells, i.e., the uptake of CE without degradation of HDL protein. Mice with attenuated expression of SR-BI, because of targeted gene mutation (SR-BIatt mice), have increased plasma HDL levels as a result of decreased selective uptake in the liver. To further evaluate the role of SR-BI in lipoprotein metabolism, compound apolipoprotein E knock-out (apoE0)/SR-BIatt mice were bred. Hepatic SR-BI protein was increased (2.3-fold) in apoE0 mice compared with wild type (wt) and was reduced significantly in apoE0/SR-BIatt mice. However, the plasma lipoprotein profile of apoE0 and apoE0/SR-BIatt mice was identical. This was explained by HDL turnover studies that revealed that the selective clearance of HDL CE by the liver and adrenal was already profoundly impaired in apoE0 mice compared with wt (28% of wt in liver). A similar decrease in selective uptake was seen when apoE0 HDL was incubated with isolated apoE0 hepatocytes. The results suggest that apoE plays a major role in the selective clearance of HDL CE by the liver and adrenal gland, possibly by facilitating the presentation of HDL to SR-BI at the cell surface.

Targeted linearization of DNA in vivo.

In the past decade, site-specific chromosomal DNA cleavage mediated by DNA endonucleases has been used to examine diverse aspects of chromosome structure and function in eukaryotes, such as DNA topology, replication, transcription, recombination, and repair. Here we describe a method with which chromosomes can be linearized at any predefined position in vivo. Yeast homothallic switching endonuclease (HO endo), a sequence-specific double-strand nuclease involved in mating-type switching, is employed for targeting DNA cleavage. HO endo contains discrete functional domains: a N-terminal nuclease and a C-terminal DNA-binding domain, thereby allowing construction of a chimeric nuclease with the cutting site distinct from the original HO recognition sequence. The expression of the nuclease is engineered to be controlled by a tightly regulated, inducible promoter. The cut sites recognized by HO endo or its derivatives are introduced specifically at desired positions in the yeast genome by homologous recombination. Here we present experimental procedures and review some applications based on this approach in yeast and other biological systems.

Template topology and transcription: chromatin templates relaxed by localized linearization are transcriptionally active in yeast.

To address the role of transient torsional stress in transcription, we have utilized the regulated expression of HO endonuclease in yeast to create double-strand breaks in DNA templates in vivo at preselected sites. Linearization of circular minichromosomes, either 2 kb upstream or immediately downstream of a lacZ reporter gene controlled by the yeast metallothionein gene (CUP1) promoter, did not alter the copper induction profile of lacZ RNA transcripts compared to that of nonlinearized controls. Constructs site-specifically integrated into yeast chromosome II gave similar results. In vivo cross-linking with psoralen as a probe for negative DNA supercoiling demonstrated that template linearization efficiently dissipated DNA supercoiling induced by transcription. Therefore, the efficient transcription of linearized, relaxed templates found here demonstrates that transient torsional tension is not required for transcription of chromatin templates in yeast.

[Cysts of ciliary body epithelium].

Among 1352 eyes examined histopathologically, ciliary body epithelial cysts were found in 198 eyes. The cysts can be divided into 3 types: non-pigmented epithelial, pigmented epithelial and intra-epithelial cysts, the non-pigmented epithelial cysts being the most commonly seen. The former 2 types are formed by the proliferation of the inner and outer layer of the optic cup respectively and the formation of the latter one is related to the separation of the 2 layers of the cup. The cysts can be single or multiple, at most 14 non-pigmented ciliary epithelial cysts with 2 iris epithelial cysts being present in one eye. The incidence of ciliary epithelial cysts is as high as 14.6%. Because of the hidden position, clinical doctors seldom notice them. They can be misdiagnosed as melanoma, they can cause secondary glaucoma and localized cataract and they can be detached spontaneously. Therefore, clinical doctors ought to pay attention to this disease.

[Factors affecting stroke patients' motivations for rehabilitation].

Factors correlated to the motivation for rehabilitation in stroke patients were studied. Thirty patients who had had only one stroke were recruited between December 1991 and April 1992 for our study. Several assessment tools including the Motivational scale, the Health Locus of Control scale and a questionnaire were used. According to the results of the assessment, the stroke patients' motivation remained stable when assessed two to three times during the hospital stay, whereas their UE/LE Brunnstrom stage scores and activities of daily living skill (ADL) improved significantly. The motivation of the patients was closely correlated with the degree of education, the internal scores and ADL performance: patients with education level higher than primary school, higher internal scores, or better ADL performance had stronger motivation for rehabilitation. On the other hand, motivational assessments between the nursing staff and the therapists were not completely in agreement. The ADL performance was better correlated with the degree of motivation on the nursing assessment, whereas the Brunnstrom stage scores of UE/LE were more closely correlated with the therapists' assessment. Items on the motivational questionnaire such as "eagerness to recover earlier", "recognition of the effectiveness of rehabilitation", "support of spouse" and "homesickness" were commonly considered to be positive factors. However, the other factors such as "being in bad mood", "lack of family cooperation", "worrying about things other than finances" and "lack of family support" were commonly considered to be negative factors on motivation. In the comparison between high and low motivation groups, the high motivation group payed more attention to the positive factors such as "eagerness to be independent" and such negative factors as "lack of understanding of illness" as well as "poor appetite and fatigue". The low motivation group was considered to be more affected by such negative factors as "worrying about things other than finances", "not good enough facilities" and "homesickness" which resulted in lessening the motivation for rehabilitation.

Deletion studies to reveal the basis for size discrepancy in proliferating cell nuclear antigen.

Proliferating cell nuclear antigen (PCNA), an essential component for DNA replication in eukaryotes, is a highly conserved nonhistone nuclear protein of 261 amino acids. The molecular weight of mammalian PCNA, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), differs notably from that predicted by the cDNA sequences, that is, 36,000 in comparison with 29,261 and 28,748 for human and rat PCNA, respectively. To investigate if this discrepancy is due to posttranslational modifications, we studied the PCNA protein synthesized by an in vitro transcription/translation system as well as the protein overproduced in bacteria. We found that both PCNA protein samples were indistinguishable from the authentic protein from the protein mobility in SDS-PAGE. The finding indicates that the size discrepancy is not due to the posttranslational modifications. Hence, the size discrepancy may be due to the protein sequence per se, namely a sequence-related anomaly in SDS-PAGE. Results from the analyses of a series of PCNA derivatives with various lengths of C- or N-terminal deletion indicate that the putative sequence is in the region of residues 128-150.