Characterization of High-Temperature Superconductor Bulks for Electrical Machine Application

High-temperature superconducting (HTS) bulks can be used in electrical applications. Experimental characterization of large-size HTS bulks is a tricky issue. The relevant parameters for their application were directly measured in this study. This paper has three main aims. Firstly, features of YBaCuO bulks are presented. Secondly, an electrical motor application is developed using magnetic field shielding and trapping. Thirdly, the HTS bulks are characterized. Several classical methods were used, which are mainly magnetic methods only available for small samples. The complete penetration magnetic field and the critical current density were found to be the main parameters relevant for applications. An innovative entire HTS bulk characterization method is presented. This characterization method is useful for end users and engineers to better implement HTS bulks.     

Anesthetic-induced alteration in expression of myocardial calcium cycling proteins

OBJECTIVE: The purpose of this study was to test the hypothesis that anesthesia alone or in combination with high F(I)(O)2 alters expression of the myocardial calcium cycling proteins, sarcoplasmic endoreticular calcium adenosine triphosphatase subtype 2a (SERCA2a), and the sarcolemmal sodium-calcium exchanger (NCX). DESIGN: Multigroup comparison of protein expression using analysis of variance. SETTING: University research laboratory. SUBJECTS: Twenty-seven New Zealand white rabbits. INTERVENTIONS: After sedation and the induction of anesthesia, animals underwent either tracheal intubation and ventilation for 5 hours with 1.0% end-tidal halothane in oxygen (HAL-O(2) , n = 5) or air (HAL-air, n = 5) or time-control recovery while spontaneously breathing oxygen (TC-O(2) , n = 5) or air (TC-air, n = 5) for 5 hours. Halothane dose was based on pilot data from 2 rabbits. Animals were then sacrificed, and the hearts were removed for Western blot analysis. Data were normalized to those from a group of rabbits immediately sacrificed (n = 5) without any prior treatment. MEASUREMENTS AND MAIN RESULTS: In comparison to their respective time controls, SERCA2a was decreased 23 % in both HAL-air and HAL-O(2) groups, whereas NCX was increased 34% and 122%, respectively. Expression was distinctly different between HAL-air and HAL-O(2) for both SERCA2a (p = 0.009) and NCX (p < 0.001), indicating an influence of high F(I)O(2). Similarly, SERCA2a in the TC-O(2) group was reduced 25% relative to the TC-air group. CONCLUSION: Halothane alters the expression of myocardial calcium cycling proteins, and this effect is potentiated by high F(I)O(2) . These data offer the broad conclusion that perioperative interventions may influence the study of myocardial molecular remodeling and suggest the possibility of anesthetic-induced myocardial molecular remodeling.     

体质医学概说

简述了体质医学在西方发展情况以及受重视的原因,并且说明了它在预防疾病和治疗疾病中的重要作用。     

Stimulation of kainate toxicity by zinc in cultured cerebellar granule neurons and the role of mitochondria in this process

Zinc chloride (0.01 mM kept for 3 h) is not toxic to cultured cerebellar granule neurons (CGNs) while kainate (0.1 mM kept for 3 h) demonstrates some but very low toxicity towards these cells.Measurements of the relative intraneuronal zinc ion concentration showed that increase in [Zn²⁺]_i under the simultaneous action of ZnCl₂ and kainate was significantly stronger compared to their separate action. Simultaneous treatment of CGNs with kainate and zinc chloride caused the swelling of neuronal mitochondria and consequent intensive neuronal death, which was totally prevented by NBQX (an AMPA/kainate-receptors blocker) or ruthenium red (a mitochondrial Ca²⁺ uniporter blocker). These data imply that Zn²⁺ synergistically to kainate increase their separate toxic effects on mitochondria leading to rapid neuronal death.     

Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels

Tunneling nanotubes (TNTs) are recently discovered conduits for a previously unrecognized form of cell-to-cell communication. These nanoscale, F-actin–containing membrane tubes connect cells over long distances and facilitate the intercellular exchange of small molecules and organelles. Using optical membrane-potential measurements combined with mechanical stimulation and whole-cell patch-clamp recording, we demonstrate that TNTs mediate the bidirectional spread of electrical signals between TNT-connected normal rat kidney cells over distances of 10 to 70 μm. Similar results were obtained for other cell types, suggesting that electrical coupling via TNTs may be a widespread characteristic of animal cells. Strength of electrical coupling depended on the length and number of TNT connections. Several lines of evidence implicate a role for gap junctions in this long-distance electrical coupling: punctate connexin 43 immunoreactivity was frequently detected at one end of TNTs, and electrical coupling was voltage-sensitive and inhibited by meclofenamic acid, a gap-junction blocker. Cell types lacking gap junctions did not show TNT-dependent electrical coupling, which suggests that TNT-mediated electrical signals are transmitted through gap junctions at a membrane interface between the TNT and one cell of the connected pair. Measurements of the fluorescent calcium indicator X-rhod-1 revealed that TNT-mediated depolarization elicited threshold-dependent, transient calcium signals in HEK293 cells. These signals were inhibited by the voltage-gated Ca²⁺ channel blocker mibefradil, suggesting they were generated via influx of calcium through low voltage-gated Ca²⁺ channels. Taken together, our data suggest a unique role for TNTs, whereby electrical synchronization between distant cells leads to activation of downstream target signaling.Cell-to-cell communication plays an important role in physiological processes of multicellular organisms. Diverse signaling pathways have been documented for the exchange of molecular information between cells. These include (i) the direct interaction of cell-surface molecules, (ii) the secretion of signaling molecules and their receptor-mediated uptake by target cells, and (iii) the direct transport of molecules through gap junctions. In addition to the exchange of signaling molecules, cells also communicate via electrical signals, where electrical coupling of cells via gap junctions is crucial for information processing and synchronization. Recent studies implicate electrical signaling in developmental processes, such as the establishment of left-right pattern in embryos (1), tail regeneration of Xenopus (2), and wound healing (2).Some years ago, a new route of intercellular communication, based on the formation of tunneling nanotubes (TNTs) or similar structures that connect cells over long distances, was identified (3, 4). These membrane tubes, typically 50 to 200 nm in diameter with lengths up to several cell diameters, contain F-actin and, as a characteristic property, lack contact to the substratum (5). Subsequently, a growing number of cell types have been shown to form and use TNTs for the exchange of diverse cellular components, such as endocytic vesicles, mitochondria, plasma membrane proteins, and cytoplasmic molecules (6, 7). Pathogens, such as HIV (8, 9) and prions (10), have also been found to spread via TNT-like structures. The increasing number of functions attributed to TNTs (6, 7, 11), in conjunction with the recent finding that these structures exist in vivo (12), suggests important roles in intercellular communication of TNTs under physiological conditions.The question arises as to whether, in addition to the exchange of molecules, TNTs also convey electrical signals between distant cells. The demonstration that artificial membrane nanotubes with a similar diameter as TNTs are efficient conductors of electrical currents (13) suggests that TNTs may also accomplish electrical cell-to-cell coupling. To investigate this theory, we combined optical membrane-potential measurements and electrophysiological methods to analyze electrical signals between TNT-connected cell pairs. Our results demonstrate that TNTs can mediate electrical coupling between distant cells and provide evidence that gap junctions participate in this long-distance coupling. Furthermore, we show that the electrical signals transferred from one cell to another are sufficient to induce a transient calcium elevation in the recipient cell by activating low voltage-gated Ca²⁺ channels.     

Liposomal Simvastatin Attenuates Neointimal Hyperplasia in Rats

Monocytes, macrophages, and inflammation play a key role in the process of neointimal proliferation and restenosis. The present study evaluated whether systemic and transient depletion of monocytes could be obtained by a single intravenous (IV) injection of simvastatin liposomes, for the inhibition of neointima formation. Balloon-injured carotid artery rats (n = 30) were randomly assigned to treatment groups of free simvastatin, simvastatin in liposomes (3 mg/kg), and saline (control). Stenosis and neointima to media ratio (N/M) were determined 14 days following single IV injection at the time of injury by morphometric analysis. Depletion of circulating monocytes was determined by flow cytometry analyzes of blood specimens. Inhibition of RAW264.7, J774, and THP-1 proliferation by simvastatin-loaded liposomes and free simvastatin was determined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5- diphenyltetrazolium bromide assay. Simvastatin liposomes were successfully formulated and were found to be 1.5-2 times more potent than the free drug in suppressing the proliferation of monocytes/macrophages in cell cultures of RAW 264.7, J774, and THP-1. IV injection of liposomal simvastatin to carotid-injured rats (3 mg/kg, n = 4) resulted in a transient depletion of circulating monocytes, significantly more prolonged than that observed following treatment with free simvastatin. Administration to balloon-injured rats suppressed neointimal growth. N/M at 14 days was 1.56 ± 0.16 and 0.90 ± 0.12, control and simvastatin liposomes, respectively. One single systemic administration of liposomal simvastatin at the time of injury significantly suppresses neointimal formation in the rat model of restenosis, mediated via a partial and transient depletion of circulating monocytes.Key words: drug delivery systems, liposomes, monocytes, restenosis, statins     

Evaluation of health-care utilization among adult patients with epilepsy in Germany

This study evaluated the resource use of patients with epilepsy in the German district of Marburg-Biedenkopf. A cross-sectional cohort of consecutive adults with epilepsy, irrespective of seizure severity, duration of illness and epilepsy syndrome, was investigated in all health-care sectors. Costs of inpatient and outpatient treatment were derived from billing data of participating hospitals and office-based physicians. Data on socioeconomic status, course of epilepsy and further direct and indirect costs were recorded using patient questionnaires. We enrolled 366 patients from the district of Marburg-Biedenkopf and calculated annual epilepsy-specific costs of €7738 per patient. Direct costs contributed 31.1% (€2406) and indirect costs 68.9% (€5332) of the total costs. Direct medical costs were mainly due to hospitalization (33.2% of total direct costs) and anticonvulsants (26.7%). Costs of admissions were due to status epilepticus (24.4%), video-EEG monitoring (14.8%), newly diagnosed patients (14.4%) and seizure-related injuries (8.8%). Indirect costs were mainly due to early retirement (38.0%), unemployment (35.9%) and days off due to seizures (26.2%). The mean costs of epilepsy found in our study were lower than those found in studies conducted at European epilepsy centers due to the inclusion of patients in all health-care sectors.     

Two new insulator proteins,Pita and ZIPIC,target CP190 to chromatin

Insulators are multiprotein–DNA complexes that regulate the nuclear architecture. The Drosophila CP190 protein is a cofactor for the DNA-binding insulator proteins Su(Hw), CTCF, and BEAF-32. The fact that CP190 has been found at genomic sites devoid of either of the known insulator factors has until now been unexplained. We have identified two DNA-binding zinc-finger proteins, Pita, and a new factor named ZIPIC, that interact with CP190 in vivo and in vitro at specific interaction domains. Genomic binding sites for these proteins are clustered with CP190 as well as with CTCF and BEAF-32. Model binding sites for Pita or ZIPIC demonstrate a partial enhancer-blocking activity and protect gene expression from PRE-mediated silencing. The function of the CTCF-bound MCP insulator sequence requires binding of Pita. These results identify two new insulator proteins and emphasize the unifying function of CP190, which can be recruited by many DNA-binding insulator proteins.Insulators in the Drosophila and vertebrate genomes have been identified based on their ability to disrupt the communication between an enhancer and a promoter when inserted between them (Raab and Kamakaka 2010; Ghirlando et al. 2012; Herold et al. 2012; Matzat and Lei 2013; Chetverina et al. 2014; Kyrchanova and Georgiev 2014). The growing amount of data show that insulator proteins fulfil an architectural function in mediating inter- and intrachromosomal interactions and in contacting regulatory elements such as promoters or enhancers (Maksimenko and Georgiev 2014).The best studied Drosophila insulator proteins, dCTCF (homolog of vertebrate insulator protein CTCF) and Su(Hw) are DNA-binding zinc-finger proteins (Herold et al. 2012; Matzat and Lei 2013; Kyrchanova and Georgiev 2014). Binding sites for dCTCF have been identified in the insulators that separate functional regulatory domains of the bithorax complex and in many promoter regions (Moon et al. 2005; Holohan et al. 2007; Mohan et al. 2007; Nègre et al. 2010, 2011; Ni et al. 2012). The Su(Hw) protein more frequently associates with intergenic sites (Adryan et al. 2007; Bushey et al. 2009; Nègre et al. 2010, 2011; Soshnev et al. 2012, 2013). As shown in a transgenic assay, dCTCF and Su(Hw) binding sites can support specific distant interactions (Kyrchanova et al. 2008a,b), which suggests a key role for these proteins in organizing chromatin architecture.The Su(Hw), dCTCF, and BEAF-32 proteins interact with Centrosomal Protein 190 kD, named CP190 (Pai et al. 2004; Gerasimova et al. 2007; Mohan et al. 2007; Bartkuhn et al. 2009; Oliver et al. 2010; Liang et al. 2014). CP190 (1096 amino acids) contains an N-terminal BTB/POZ domain, an aspartic-acid-rich D-region, four C2H2 zinc-finger motifs, and a C-terminal E-rich domain (Oliver et al. 2010; Ahanger et al. 2013). The BTB domain of CP190 forms stable homodimers that may be involved in protein–protein interactions (Oliver et al. 2010; Bonchuk et al. 2011). In addition to these motifs, CP190 also contains a centrosomal targeting domain (M) responsible for its localization to centrosomes during mitosis (Butcher et al. 2004). It has been shown that CP190 is recruited to chromatin via its interaction with the Su(Hw) and dCTCF proteins (Pai et al. 2004; Mohan et al. 2007). Inactivation of CP190 affects the activity of the dCTCF-dependent insulator Fab-8 from the bithorax complex (Gerasimova et al. 2007; Mohan et al. 2007; Moshkovich et al. 2011) and the gypsy insulator, which contains 12 binding sites for the Su(Hw) protein (Pai et al. 2004). Binding of Su(Hw) and CP190 at gypsy-like sites is mutually dependent, indicating a stabilizing role of CP190 in these cases (Schwartz et al. 2012).Recent genome-wide ChIP-chip studies provide evidence for an extensive overlap of the CP190 distribution pattern with dCTCF, BEAF-32, and Su(Hw) insulator proteins and the promoters of active genes (Bartkuhn et al. 2009; Bushey et al. 2009; Nègre et al. 2010, 2011; Schwartz et al. 2012; Soshnev et al. 2012). Very recently, it has been demonstrated that CP190 bridges DNA-bound insulator factors with promoters (Liang et al. 2014). These data support the model that CP190 has a global role in the function of insulator proteins. However, there are a number of sites in the Drosophila genome where CP190 does not colocalize with any known insulator DNA binding protein (IBP), suggesting that there may be some other proteins that recruit CP190 to chromatin (Schwartz et al. 2012).To identify new factors that associate with CP190, we purified the FLAG-tagged CP190 protein from S2 cells and identified two zinc-finger proteins, CG7928 and Pita, which were shown to interact with CP190 in vivo and in vitro. Genome-wide identification of binding sites for Pita and CG7928 in S2 cells revealed their extensive colocalization with CP190, providing evidence for direct interactions between these proteins, which was supported by binding and in vivo functional assays. Based on these results we termed CG7928 the “zinc-finger protein interacting with CP190” (ZIPIC).