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In this study, we investigate the spin Hall effect in heterostructures of Bi0.85Sb0.15 (10 nm) topological insulator/Ru(Ti)/Ta/Co20Fe60B20/MgO with perpendicular magnetic anisotropy. By optimizing the Ru (Ti) interfacial layer thickness as well as deposition condition of BiSb, we achieve a large effective spin Hall angle of 6.0 ± 0.1 and relatively high electrical conductivity of 1.5 × 105 Ω−1 m−1 at room temperature. We, then, demonstrate spin–orbit torque-induced magnetization switching driven by a small threshold current density of 1 × 106 Acm−2. Benchmarking shows that the writing power consumption of our stack is 2–3 orders smaller than that of heavy metals. [ABSTRACT FROM AUTHOR]

It has been shown that Escherichia coli cells with increased expression of the rpoE gene encoding [[sigma].sup.E] exhibit enhanced cell lysis in early stationary phase. Further analysis of the lysis phenomenon was performed using a transient expression system of the rpoE gene and by DNA microarray. The former analysis revealed a [[sigma].sup.E]-directed cell lysis, specific for early stationary phase but not for the exponential phase. The microarray analysis with RNAs from exponential and early stationary phase cells revealed that a large number of genes were up-or down-regulated when the rpoE gene was induced, and that several genes were induced in a phase-specific manner. The upregulated genes include many previously identified [[sigma].sup.E] regulon genes, suggesting that a large number of genes are under the control of [[sigma].sup.E] in this organism. These genes are involved in various cellular activities, including the cell envelope, cellular processes, regulatory functions, transport and translation. Genes that are presumably related to phase-specific cell lysis in E. coli are discussed.

We used a micromagnetic model to study the head remanence of a perpendicular tapered main pole head. To reduce the head pole tip remanence, a single magnetic domain structure forming a vortex state from the pole tip to the tapered region is preferred. A tapered main pole structure with a trailing gap depth less than about 30 nm and a tapered angle (TGθ) equal to about 30° improved the writing efficiency. This was achieved with a head field value more than 1.3 times higher and with a head field gradient about 1.15 times higher than that of the conventional structure. Moreover, the pole tip remanence was reduced to a value closer to that of the conventional structure. The reduction in the throat height had less effect on the reduction in the head remanence in the tapered head than in the conventional head. We also discuss both single pole heads and shielded heads. [ABSTRACT FROM AUTHOR]

Hybrid lead halide perovskites have emerged as promising active materials for photovoltaic cells. Although superb efficiencies have been achieved, it is widely recognized that long-term stability is a key challenge intimately determining the future development of perovskite-based photovoltaic technology. Herein, we present reversible and irreversible photodecomposition reactions of methylammonium lead iodide (MAPbI3). Simulated sunlight irradiation and temperature (40–80 °C) corresponding to solar cell working conditions lead to three degradation pathways: (1) CH3NH2 + HI (identified as the reversible path), (2) NH3 + CH3I (the irreversible or detrimental path), and (3) a reversible Pb(0) + I2(g) photodecomposition reaction. If only the reversible reactions EQNREF(1)/EQNREF and EQNREF(3)/EQNREF take place and reaction EQNREF(2)/EQNREF can be avoided, encapsulated MAPbI3 can be regenerated during the off-illumination timeframe. Therefore, to further improve operational stability in hybrid perovskite solar cells, detailed understanding of how to mitigate photodegradation and thermal degradation processes is necessary. First, encapsulation of the device is necessary not only to avoid contact of the perovskite with ambient air, but also to prevent leakage of volatile products released from the perovskite. Second, careful selection of the organic cations in the compositional formula of the perovskite is necessary to avoid irreversible reactions. Third, selective contacts must be as chemically inert as possible toward the volatile released products. Finally, hybrid halide perovskite materials are speculated to undergo a dynamic formation and decomposition process; this can gradually decrease the crystalline grain size of the perovskite with time; therefore, efforts to deposit highly crystalline perovskites with large crystal sizes may fail to increase the long-term stability of photovoltaic devices. [ABSTRACT FROM AUTHOR]

Ribosomes routinely prepared from Escherichia coli strain K12 contain intact (70 amino acids) and short (62 amino acids) forms of ribosomal protein L31. By contrast, ribosomes prepared from ompT mutant cells, which lack protease 7, contain only intact L31, suggesting that L31 is cleaved by protease 7 during ribosome preparation. We compared ribosomal subunit association in wild-type and ompT − strains. In sucrose density gradient centrifugation under low Mg2+, 70S content was very high in ompT − ribosomes, but decreased in the wild-type ribosomes containing short L31. In addition, ribosomes lacking L31 failed to associate ribosomal subunits in low Mg2+. Therefore, intact L31 is required for subunit association, and the eight C-terminal amino acids contribute to the association function. In vitro translation was assayed using three different systems. Translational activities of ribosomes lacking L31 were 40% lower than those of ompT − ribosomes with one copy of intact L31, indicating that L31 is involved in translation. Moreover, in the stationary phase, L31 was necessary for 100S formation. The strain lacking L31 grew very slowly. A structural analysis predicted that the L31 protein spans the 30S and 50S subunits, consistent with the functions of L31 in 70S association, 100S formation, and translation. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC. Methods and Findings: Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99±1.8 µg/ml in men and 6.06±2.1 µg/ml in women. AIM levels were significantly augmented in the younger generation (20s–40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis. Conclusion: AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease. [ABSTRACT FROM AUTHOR]

In yeast, C-tail-anchored mitochondrial outer membrane protein Fis1 recruits the mitochondrial-fission-regulating GTPase Dnm1 to mitochondrial fission sites. However, the function of its mammalian homologue remains enigmatic because it has been reported to be dispensable for the mitochondrial recruitment of Drp1, a mammalian homologue of Dnm1. We identified TBC1D15 as a Fis1-binding protein in HeLa cell extracts. Immunoprecipitation revealed that Fis1 efficiently interacts with TBC1D15 but not with Drp1. Bacterially expressed Fis1 and TBC1D15 formed a direct and stable complex. Exogenously expressed TBC1D15 localized mainly in cytoplasm in HeLa cells, but when coexpressed with Fis1 it localized to mitochondria. Knockdown of TBC1D15 induced highly developed mitochondrial network structures similar to the effect of Fis1 knockdown, suggesting that the TBC1D15 and Fis1 are associated with the regulation of mitochondrial morphology independently of Drp1. These data suggest that Fis1 acts as a mitochondrial receptor in the recruitment of mitochondrial morphology protein in mammalian cells. [ABSTRACT FROM AUTHOR]

Mitochondrial morphology is dynamically controlled by a balance between fusion and fission. The physiological importance of mitochondrial fission in vertebrates is less clearly defined than that of mitochondrial fusion. Here we show that mice lacking the mitochondrial fission GTPase Drp1 have developmental abnormalities, particularly in the forebrain, and die after embryonic day 12.5. Neural cell-specific (NS) Drp1−/− mice die shortly after birth as a result of brain hypoplasia with apoptosis. Primary culture of NS-Drp1−/− mouse forebrain showed a decreased number of neurites and defective synapse formation, thought to be due to aggregated mitochondria that failed to distribute properly within the cell processes. These defects were reflected by abnormal forebrain development and highlight the importance of Drp1-dependent mitochondrial fission within highly polarized cells such as neurons. Moreover, Drp1−/− murine embryonic fibroblasts and embryonic stem cells revealed that Drp1 is required for a normal rate of cytochrome c release and caspase activation during apoptosis, although mitochondrial outer membrane permeabilization, as examined by the release of Smac/Diablo and Tim8a, may occur independently of Drp1 activity. [ABSTRACT FROM AUTHOR]

In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, ∼500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system. Synapse 56:175-184, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

To achieve industrially viable fabrication process for perovskite-based solar cells, every process step must be optimized for maximum throughput. We present a study of substituting laboratory-type UV-Ozone surface treatment with a high-throughput Corona treatment in a scalable perovskite solar cell fabrication process. It is observed that water contact angle measurements provide insufficient information to determine the necessary dose of Corona or UV-Ozone treatment, but the surface carbon signal measured by x-ray photoelectron spectroscopy accurately identifies when surface contamination has been completely removed. Furthermore, we observe highly accelerated de-contamination of ZnO surfaces by UV-Ozone treatment. The effect can be explained by photocatalytic O 2 − ion generation indicating that UV-Ozone treatment is also applicable in high-throughput processing. [ABSTRACT FROM AUTHOR]

Summary Mitochondria are dynamic organelles that change their morphology by active fusion and fission in response to cellular signaling and differentiation [ 1, 2 ]. The in vivo role of mitochondrial fission in mammals has been examined by using tissue-specific knockout (KO) mice of the mitochondria fission-regulating GTPase Drp1 [ 3, 4 ], as well as analyzing a human patient harboring a point mutation in Drp1 [ 5 ], showing that Drp1 is essential for embryonic and neonatal development and neuronal function. During oocyte maturation and aging, structures of various membrane organelles including mitochondria and the endoplasmic reticulum (ER) are changed dynamically [ 6, 7 ], and their organelle aggregation is related to germ cell formation and epigenetic regulation [ 8–10 ]. However, the underlying molecular mechanisms of organelle dynamics during the development and aging of oocytes have not been well understood. Here, we analyzed oocyte-specific mitochondrial fission factor Drp1-deficient mice and found that mitochondrial fission is essential for follicular maturation and ovulation in an age-dependent manner. Mitochondria were highly aggregated with other organelles, such as the ER and secretory vesicles, in KO oocyte, which resulted in impaired Ca 2+ signaling, intercellular communication via secretion, and meiotic resumption. We further found that oocytes from aged mice displayed reduced Drp1-dependent mitochondrial fission and defective organelle morphogenesis, similar to Drp1 KO oocytes. On the basis of these findings, it appears that mitochondrial fission maintains the competency of oocytes via multiorganelle rearrangement. [ABSTRACT FROM AUTHOR]

Investigates the proteolytic activity of YibP protein in Escherichia coli. Structure of E. coli YibP protein; Disintegration of the substrate beta-casein by YibP protease activity; Expression of YibP domains in the cytoplasmic space.

It has been shown that Escherichia coil cells with increased expression of the rpoE gene encoding αE exhibit enhanced cell lysis in early stationary phase. Further analysis of the lysis phenomenon was performed using a transient expression system of the rpoE gene and by DNA microarray. The former analysis revealed a αE directed cell lysis, specific for early stationary phase but not for the exponential phase. The microarray analysis with RNAs from exponential and early stationary phase cells revealed that a large number of genes were up- or down-regulated when the rpoE gene was induced, and that several genes were induced in a phase-specific manner. The upregulated genes include many previously identified αE regulon genes. suggesting that a large number of genes are tinder the control of αE in this organism. These genes are involved in various cellular activities, including the cell envelope, cellular processes, regulatory functions, transport and translation. Genes that are presumably related to phase-specific cell lysis in E. coli are discussed. [ABSTRACT FROM AUTHOR]

Introduction: High-dose erythropoietin (EPO) administration to hemodialysis (HD) patients with EPO hyporesponsiveness, due to iron deficiency, hyperparathyroidism, malnutrition, inflammation, and inadequate HD, results in increased risk of mortality and cardiovascular events. We investigated the relationship of the EPO dose requirement with 4-, 5-, and 6-hour HD treatment times., Materials and Methods: This cross-sectional study enrolled 300 HD patients, including those on 4-hour HD (n = 78), 5-hour HD (n = 106), and 6-hour HD (n = 116). We studied the following parameters: weekly EPO dose, hemoglobin (Hb), serum ferritin, Kt/V, membrane surface area, quantity of blood flow, quantity of dialysate flow, age, HD vintage, serum albumin, C-reactive protein (CRP), intact parathyroid hormone (iPTH), and β2-microglobulin. These parameters were analyzed with JMP9 TM statistical software., Findings: The EPO requirement (units per week) of the 6-hour HD group (4,035 ± 269) was significantly lower than that of the 5-hour HD group (6,628 ± 630), which was significantly lower than that of the 4-hour HD group (8,567 ± 684). The Hb level, mean corpuscular volume, quantity of blood flow, quantity of dialysate flow, age, gender, ratio of diabetic patients, body mass index, dry weight, CRP, iPTH, use of antiplatelet agents and anticoagulants were not significantly different among the three groups. Multiple regression analysis with the weekly EPO requirement as the dependent variable showed HD treatment time (p < 0.0001) and CRP level (p < 0.001) as the significant independent variables., Discussion: The EPO dose can be reduced by ~ 2,000 U/week by extending the HD treatment time for 1 hour; annual cost savings were calculated to be USD 570 per patient.

Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis, including mitochondrial DNA (mtDNA) distribution. Cardiac myocytes have a specialized cytoplasmic structure where large mitochondria are aligned into tightly packed myofibril bundles; however, recent studies have revealed that mitochondrial dynamics also plays an important role in the formation and maintenance of cardiomyocytes. Here, we precisely analyzed the role of mitochondrial fission in vivo. The mitochondrial fission GTPase, Drp1, is highly expressed in the developing neonatal heart, and muscle-specific Drp1 knockout (Drp1-KO) mice showed neonatal lethality due to dilated cardiomyopathy. The Drp1 ablation in heart and primary cultured cardiomyocytes resulted in severe mtDNA nucleoid clustering and led to mosaic deficiency of mitochondrial respiration. The functional and structural alteration of mitochondria also led to immature myofibril assembly and defective cardiomyocyte hypertrophy. Thus, the dynamics of mtDNA nucleoids regulated by mitochondrial fission is required for neonatal cardiomyocyte development by promoting homogeneous distribution of active mitochondria throughout the cardiomyocytes., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Gingipains are cysteine proteinases that are responsible for the virulence of Porphyromonas gingivalis. Recent studies have shown that P. gingivalis is trapped within autophagic compartments of infected cells, where it promotes survival. In this study we investigated the role of gingipains in the intracellular trafficking and survival of this bacterium in human aortic endothelial cells and any possible involvement of these enzymes in the autophagic pathway. Although autophagic events were enhanced by infection with either wild-type (WT) P. gingivalis strains (ATCC 33277, 381, and W83) or an ATCC 33277 mutant lacking gingipains (KDP136), we have found that more than 90% of intracellular WT and KDP136 colocalized with cathepsin B, a lysosome marker, and only a few of the internalized cells colocalized with LC3, an autophagosome marker, during the 0.5- to 4-h postinfection period. This was further substantiated by immunogold electron microscopic analyses, thus implying that P. gingivalis evades the autophagic pathway and instead directly traffics to the endocytic pathway to lysosomes. At the late stages after infection, WT strains in phagolysosomes retained their double-membrane structures. KDP136 in these compartments, however, lost its double-membrane structures, representing a characteristic feature of its vulnerability to rupture. Together with the ultrastructural observations, we found that the number of intracellular viable WT cells decreased more slowly than that of KDP136 cells, thus suggesting that gingipains contribute to bacterial survival, but not to trafficking, within the infected cells.

We cloned a approximately 70 kDa rat mitochondrial outer membrane protein (OM70) with a sequence identity of 28.1% and 20.1% with N. crassa and S. cerevisiae Tom70, respectively. Even with this low sequence identity, however, the proteins share a remarkable structural similarity: they have 7-10 tetratricopeptide repeat motifs and are anchored to the outer membrane through the N-terminal transmembrane domain with the bulk portion located in the cytosol. Antibodies against OM70 inhibited import of preproteins, such as the ADP/ATP carrier and rTOM40, that use internal targeting signals but not the import of cleavable presequence-containing preproteins. Blue native gel electrophoresis and immunoprecipitation of digitoninsolubilized mitochondrial outer membranes revealed that OM70 was loosely associated with the approximately 400 kDa translocase complex of the mitochondrial outer membrane, which contains rTOM22 and rTOM40. A yeast two-hybrid system demonstrated that OM70 interacted with rTOM20 and rTOM22 through the cytoplasmic domains. Thus, OM70 is a functional homologue of fungal Tom70 and functions as a receptor of the preprotein import machinery of the rat mitochondrial outer membrane. Furthermore, the N-terminal 66 residue region of OM70, which comprises a hydrophilic 41 residue N-terminal domain, a 22 residue transmembrane domain and three arginine residues, is sufficient to act as a mitochondria-targeting signal, and the arginine cluster is crucial for this function.

The fifth component of the COP9 signalosome complex, Jab1/CSN5, directly binds to and induces specific down-regulation of the cyclin-dependent kinase inhibitor p27 (p27(Kip1)). Nuclear-cytoplasmic translocation plays an important role because leptomycin B (LMB), a chemical inhibitor of CRM1-dependent nuclear export, prevents p27 degradation mediated by Jab1/CSN5. Here we show that Jab1/CSN5 functions as an adaptor between p27 and CRM1 to induce nuclear export and subsequent degradation. Jab1/CSN5, but not p27, contains a typical leucine-rich nuclear export signal (NES) sequence conserved among different species, through which CRM1 bound to Jab1/CSN5 in an LMB-sensitive manner. Alteration of conserved leucine residues to alanine within Jab1/CSN5-NES abolished the interaction with CRM1 in vitro and impaired LMB-sensitive nuclear export and the ability to induce p27 breakdown in cultured cells. A Jab1/CSN5 truncation mutant lacking NES reversed p27 down-regulation induced by the full-length Jab1/CSN5, indicating that this mutant functions as a dominant negative (DN-Jab1). Introduction of DN-Jab1 into proliferating fibroblasts increased the level of p27 protein, thereby inducing growth arrest of the cells. Random mutagenesis analysis revealed that specific aspartic acid, leucine, and asparagine residues contained in the Jab1/CSN5-binding domain of p27 were required for interaction with Jab1/CSN5 and for down-regulation of p27. Glycerol gradient and cell fractionation experiments showed that at least two different forms of Jab1/CSN5-containing complexes existed within the cell. One is the conventional 450-kDa COP9 signalosome (CSN) complex located in the nucleus, and the other is much smaller (around 100-kDa), containing only a subset of CSN components (CSN4-8 but not CSN1-3), and mainly located in the cytoplasm. Treatment of cells with LMB greatly reduced the level of the smaller complex, suggesting that it originated from the CSN complex by nuclear export. Besides Jab1/CSN5, CSN3, -6, -7, and -8 were capable of inducing p27 down-regulation, when ectopically expressed. These results indicate that cytoplasmic shuttling regulated by Jab1/CSN5 and other CSN components may be a new pathway to control the intracellular abundance of the key cell cycle regulator.