Population genomic analysis of strain variation in Leptospirillum group II bacteria involved in acid mine drainage formation.

PubMed

Simmons, Sheri L; Dibartolo, Genevieve; Denef, Vincent J; Goltsman, Daniela S Aliaga; Thelen, Michael P; Banfield, Jillian F

2008-07-22

Deeply sampled community genomic (metagenomic) datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth approximately 20x). The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type) at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types ( approximately 94% sequence identity) have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the observed patterns of polymorphism is divergence of ancestral strains due to geographic isolation, followed by mixing and subsequent recombination.

Population Genomic Analysis of Strain Variation in Leptospirillum Group II Bacteria Involved in Acid Mine Drainage Formation

PubMed Central

Denef, Vincent J; Goltsman, Daniela S. Aliaga; Thelen, Michael P; Banfield, Jillian F

2008-01-01

Deeply sampled community genomic (metagenomic) datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth ∼20×). The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type) at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types (∼94% sequence identity) have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the observed patterns of polymorphism is divergence of ancestral strains due to geographic isolation, followed by mixing and subsequent recombination. PMID:18651792

Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of blocked angiotensin II receptors in rats.

PubMed

Mansoori, A; Oryan, S; Nematbakhsh, M

2016-03-01

The vasodilatory effect of angiotensin 1-7 (Ang 1-7) is exerted in the vascular bed via Mas receptor (MasR) gender dependently. However, the crosstalk between MasR and angiotensin II (Ang II) types 1 and 2 receptors (AT1R and AT2R) may change some actions of Ang 1-7 in renal circulation. In this study by blocking AT1R and AT2R, the role of MasR in kidney hemodynamics was described. In anaesthetized male and female Wistar rats, the effects of saline as vehicle and MasR blockade (A779) were tested on mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), and renal vascular resistance (RVR) when both AT1R and AT2R were blocked by losartan and PD123319, respectively. In male rats, when AT1R and AT2R were blocked, there was a tendency for the increase in RBF/wet kidney tissue weight (RBF/KW) to be elevated by A779 as compared with the vehicle (P=0.08), and this was not the case in female rats. The impact of MasR on renal hemodynamics appears not to be sexual dimorphism either when Ang II receptors were blocked. It seems that co-blockade of all AT1R, AT2R, and MasR may alter RBF/ KW in male more than in female rats. These findings support a crosstalk between MasR and Ang II receptors in renal circulation.

Aortic remodeling after transverse aortic constriction in mice is attenuated with AT1 receptor blockade.

PubMed

Kuang, Shao-Qing; Geng, Liang; Prakash, Siddharth K; Cao, Jiu-Mei; Guo, Steven; Villamizar, Carlos; Kwartler, Callie S; Peters, Andrew M; Brasier, Allan R; Milewicz, Dianna M

2013-09-01

Although hypertension is the most common risk factor for thoracic aortic diseases, it is not understood how increased pressures on the ascending aorta lead to aortic aneurysms. We investigated the role of angiotensin II type 1 receptor activation in ascending aortic remodeling in response to increased biomechanical forces using a transverse aortic constriction (TAC) mouse model. Two weeks after TAC, the increased biomechanical pressures led to ascending aortic dilatation and thickening of the medial and adventitial layers of the aorta. There was significant adventitial hyperplasia and inflammatory responses in TAC ascending aortas were accompanied by increased adventitial collagen, elevated inflammatory and proliferative markers, and increased cell density attributable to accumulation of myofibroblasts and macrophages. Treatment with losartan significantly blocked TAC-induced vascular inflammation and macrophage accumulation. However, losartan only partially prevented TAC-induced adventitial hyperplasia, collagen accumulation, and ascending aortic dilatation. Increased Tgfb2 expression and phosphorylated-Smad2 staining in the medial layer of TAC ascending aortas were effectively blocked with losartan. In contrast, the increased Tgfb1 expression and adventitial phospho-Smad2 staining were only partially attenuated by losartan. In addition, losartan significantly blocked extracellular signal-regulated kinase activation and reactive oxygen species production in the TAC ascending aorta. Inhibition of the angiotensin II type 1 receptor using losartan significantly attenuated the vascular remodeling associated with TAC but did not completely block the increased transforming growth factor-β1 expression, adventitial Smad2 signaling, and collagen accumulation. These results help to delineate the aortic transforming growth factor-β signaling that is dependent and independent of the angiotensin II type 1 receptor after TAC.

Vaccinia Virus Blocks Stat1-Dependent and Stat1-Independent Gene Expression Induced by Type I and Type II Interferons

PubMed Central

Mann, Brandon A.; Huang, Julia He; Li, Ping; Chang, Hua-Chen; Slee, Roger B.; O'Sullivan, Audrey; Mathur, Anita; Yeh, Norman; Klemsz, Michael J.; Brutkiewicz, Randy R.; Blum, Janice S.

2008-01-01

Blocking the function of Stat (signal transducer and activator of transcription) proteins, which are critical for antiviral responses, has evolved as a common mechanism for pathogen immune evasion. The poxvirus-encoded phosphatase H1 is critical for viral replication, and may play an additional role in the evasion of host defense by dephosphorylating Stat1 and blocking interferon (IFN)-stimulated innate immune responses. Vaccinia virus (VACV) H1 can inhibit the phosphorylation of the transcription factor Stat1 after IFN-γ stimulation of epithelial cells, greatly attenuating IFN-induced biological functions. In this study, we demonstrate that VACV infection is capable of inhibiting the phosphorylation of Stat1 and Stat2 after stimulation of fibroblasts or bone marrow-derived macrophages with either type I or type II IFNs, but did not inhibit the activation of Stat3 or Stat5 in either cell type. By using recombinant proteins for in vitro assays, we observe that variola virus H1 is more active than VACV H1, although it has similar selectivity for Stat targets. Differential effects of VACV infection were observed on the induction of IFN-stimulated genes, with complete inhibition of some genes by VACV infection, while others were less affected. Despite the IFN-γ-induced expression of some genes in VACV-infected cells, IFN-γ was unable to rescue the VACV-mediated inhibition of MHC class II antigen presentation. Moreover, VACV infection can affect the IFN-induced expression of Stat1-dependent and Stat1-independent genes, suggesting that the virus may target additional IFN-activated pathways. Thus, VACV targets multiple signaling pathways in the evasion of antiviral immune responses. PMID:18593332

Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

PubMed

Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

2011-08-01

Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection.

PubMed

Alam, S Munir; Scearce, Richard M; Parks, Robert J; Plonk, Kelly; Plonk, Steven G; Sutherland, Laura L; Gorny, Miroslaw K; Zolla-Pazner, Susan; Vanleeuwen, Stacie; Moody, M Anthony; Xia, Shi-Mao; Montefiori, David C; Tomaras, Georgia D; Weinhold, Kent J; Karim, Salim Abdool; Hicks, Charles B; Liao, Hua-Xin; Robinson, James; Shaw, George M; Haynes, Barton F

2008-01-01

Two human monoclonal antibodies (MAbs) (2F5 and 4E10) against the human immunodeficiency virus type 1 (HIV-1) envelope g41 cluster II membrane proximal external region (MPER) broadly neutralize HIV-1 primary isolates. However, these antibody specificities are rare, are not induced by Env immunization or HIV-1 infection, and are polyspecific and also react with lipids such as cardiolipin or phosphatidylserine. To probe MPER anti-gp41 antibodies that are produced in HIV-1 infection, we have made two novel murine MAbs, 5A9 and 13H11, against HIV-1 gp41 envelope that partially cross-blocked 2F5 MAb binding to Env but did not neutralize HIV-1 primary isolates or bind host lipids. Competitive inhibition assays using labeled 13H11 MAb and HIV-1-positive patient plasma samples demonstrated that cluster II 13H11-blocking plasma antibodies were made in 83% of chronically HIV-1 infected patients and were acquired between 5 to 10 weeks after acute HIV-1 infection. Both the mouse 13H11 MAb and the three prototypic cluster II human MAbs (98-6, 126-6, and 167-D) blocked 2F5 binding to gp41 epitopes to variable degrees; the combination of 98-6 and 13H11 completely blocked 2F5 binding. These data provide support for the hypothesis that in some patients, B cells make nonneutralizing cluster II antibodies that may mask or otherwise down-modulate B-cell responses to immunogenic regions of gp41 that could be recognized by B cells capable of producing antibodies like 2F5.

Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins.

PubMed

Peng, Lisheng; Berntsson, Ronnie P-A; Tepp, William H; Pitkin, Rose M; Johnson, Eric A; Stenmark, Pål; Dong, Min

2012-07-01

Botulinum neurotoxins (BoNTs) are classified into seven types (A-G), but multiple subtype and mosaic toxins exist. These subtype and mosaic toxins share a high sequence identity, and presumably the same receptors and substrates with their parental toxins. Here, we report that a mosaic toxin, type D-C (BoNT/D-C), uses different receptors from its parental toxin BoNT/C. BoNT/D-C, but not BoNT/C, binds directly to the luminal domains of synaptic vesicle proteins synaptotagmin (Syt) I and II, and requires expression of SytI/II to enter neurons. The SytII luminal fragment containing the toxin-binding site can block the entry of BoNT/D-C into neurons and reduce its toxicity in vivo in mice. We also found that gangliosides increase binding of BoNT/D-C to SytI/II and enhance the ability of the SytII luminal fragment to block BoNT/D-C entry into neurons. These data establish SytI/II, in conjunction with gangliosides, as the receptors for BoNT/D-C, and indicate that BoNT/D-C is functionally distinct from BoNT/C. We further found that BoNT/D-C recognizes the same binding site on SytI/II where BoNT/B and G also bind, but utilizes a receptor-binding interface that is distinct from BoNT/B and G. Finally, we also report that human and chimpanzee SytII has diminished binding and function as the receptor for BoNT/B, D-C and G owing to a single residue change from rodent SytII within the toxin binding site, potentially reducing the potency of these BoNTs in humans and chimpanzees.

Comparative effects of contraction and angiotensin II on growth of adult feline cardiocytes in primary culture

NASA Technical Reports Server (NTRS)

Wada, H.; Zile, M. R.; Ivester, C. T.; Cooper, G. 4th; McDermott, P. J.

1996-01-01

The purposes of this study were 1) to determine whether angiotensin II causes growth of adult feline cardiocytes in long-term culture, 2) to compare the growth effects of angiotensin II with those resulting from electrically stimulated contraction, and 3) to determine whether the anabolic effects of contraction are exerted via the angiotensin type 1 receptor. Adult feline cardiocytes were cultured on laminin-coated trays in a serum-free medium. Cardiocytes were either electrically stimulated to contract (1 Hz, 5-ms pulse duration, alternating polarity) or were nonstimulated and quiescent. Quiescent cells were studied as controls and after treatment with angiotensin II (10(-8) M), losartan (10(-6) M; an angiotensin type 1-receptor antagonist), or angiotensin II plus losartan. Contracting cells were studied in the presence and absence of angiotensin II or losartan. In quiescent cardiocytes, angiotensin II treatment on day 7 significantly increased protein synthesis rates by 22% and protein content per cell by 17%. The effects of angiotensin II were completely blocked by losartan. Electrically stimulated contraction on days 4 and 7 in culture significantly increased protein synthesis rate by 18 and 38% and protein content per cell by 19 and 46%, respectively. Angiotensin II treatment did not further increase protein synthesis rate or protein content in contracting cardiocytes. Furthermore, losartan did not block the anabolic effects of contraction on protein synthesis rates or protein content. In conclusion, angiotensin II can exert a modest anabolic effect on adult feline cardiocytes in culture. In contracting feline cardiocytes, angiotensin II has no effect on growth. Growth caused by electrically stimulated contraction occurs more rapidly and is greater in magnitude than that caused by angiotensin II. Growth of contracting adult feline cardiocytes is not dependent on activation of the angiotensin receptor.

Shear bond strength of computer-aided design and computer-aided manufacturing feldspathic and nano resin ceramics blocks cemented with three different generations of resin cement.

PubMed

Ab-Ghani, Zuryati; Jaafar, Wahyuni; Foo, Siew Fon; Ariffin, Zaihan; Mohamad, Dasmawati

2015-01-01

To evaluate the shear bond strength between the dentin substrate and computer-aided design and computer-aided manufacturing feldspathic ceramic and nano resin ceramics blocks cemented with resin cement. Sixty cuboidal blocks (5 mm × 5 mm × 5 mm) were fabricated in equal numbers from feldspathic ceramic CEREC(®) Blocs PC and nano resin ceramic Lava™ Ultimate, and randomly divided into six groups (n = 10). Each block was cemented to the dentin of 60 extracted human premolar using Variolink(®) II/Syntac Classic (multi-steps etch-and-rinse adhesive bonding), NX3 Nexus(®) (two-steps etch-and-rinse adhesive bonding) and RelyX™ U200 self-adhesive cement. All specimens were thermocycled, and shear bond strength testing was done using the universal testing machine at a crosshead speed of 1.0 mm/min. Data were analyzed using one-way ANOVA. Combination of CEREC(®) Blocs PC and Variolink(®) II showed the highest mean shear bond strength (8.71 Mpa), while the lowest of 2.06 Mpa were observed in Lava™ Ultimate and RelyX™ U200. There was no significant difference in the mean shear bond strength between different blocks. Variolink(®) II cement using multi-steps etch-and-rinse adhesive bonding provided a higher shear bond strength than the self-adhesive cement RelyX U200. The shear bond strength was not affected by the type of blocks used.

[Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

PubMed

Hu, Ying; Zou, Fei; Cai, Chun-Qing; Wu, Hang-Yu; Yun, Hai-Xia; Chen, Yun-Tian; Jin, Guo-En; Ge, Ri-Li

2006-10-25

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

He Yongzhou; Zhang Jidong; Zhou Qiaogen

Two in-vacuum undulators IVU25s and one elliptically polarized undulator EPU100 have been developed for SSRF. Two IVU25s with the same hybrid design contain about 640 Sm{sub 2}Co{sub 17} magnet blocks and the dimension of blocks is 65 Wx25 Hx9 D. The EPU100 of the APPLE-II type contains about 690 NdFeB magnet blocks with the dimension of 35 Wx35 Hx25 D. This paper describes the magnetic measurements of these magnet blocks with the Helmholtz coil measurement system for IVU25 magnet blocks and the Hall probe measurement system for EPU100 magnet blocks. The measured maximum magnetic moment deviation and the maximum anglemore » deviation are less than {+-}1.0% and 1.1 deg. respectively both for Sm{sub 2}Co{sub 17} blocks and NdFeB blocks and satisfy the specifications of undulators.« less

The human T-cell leukemia virus type 1 p13II protein: effects on mitochondrial function and cell growth

PubMed Central

D’Agostino, DM; Silic-Benussi, M; Hiraragi, H; Lairmore, MD; Ciminale, V

2011-01-01

p13II of human T-cell leukemia virus type 1 (HTLV-1) is an 87-amino-acid protein that is targeted to the inner mitochondrial membrane. p13II alters mitochondrial membrane permeability, producing a rapid, membrane potential-dependent influx of K+. These changes result in increased mitochondrial matrix volume and fragmentation and may lead to depolarization and alterations in mitochondrial Ca2+ uptake/retention capacity. At the cellular level, p13II has been found to interfere with cell proliferation and transformation and to promote apoptosis induced by ceramide and Fas ligand. Assays carried out in T cells (the major targets of HTLV-1 infection in vivo) demonstrate that p13II-mediated sensitization to Fas ligand-induced apoptosis can be blocked by an inhibitor of Ras farnesylation, thus implicating Ras signaling as a downstream target of p13II function. PMID:15761473

Interferon-induced TRAIL-independent cell death in DNase II-/- embryos.

PubMed

Kitahara, Yusuke; Kawane, Kohki; Nagata, Shigekazu

2010-09-01

The chromosomal DNA of apoptotic cells and the nuclear DNA expelled from erythroid precursors is cleaved by DNase II in lysosomes after the cells or nuclei are engulfed by macrophages. DNase II(-/-) embryos suffer from lethal anemia due to IFN-beta produced in the macrophages carrying undigested DNA. Here, we show that Type I IFN induced a caspase-dependent cell death in human epithelial cells that were transformed to express a high level of IFN type I receptor. During this death process, a set of genes was strongly activated, one of which encoded TRAIL, a death ligand. A high level of TRAIL mRNA was also found in the fetal liver of the lethally anemic DNase II(-/-) embryos, and a lack of IFN type I receptor in the DNase II(-/-) IFN-IR(-/-) embryos blocked the expression of TRAIL mRNA. However, a null mutation in TRAIL did not rescue the lethal anemia of the DNase II(-/-) embryos, indicating that TRAIL is dispensable for inducing the apoptosis of erythroid cells in DNase II(-/-) embryos, and therefore, that there is a TRAIL-independent mechanism for the IFN-induced apoptosis.

P-type Ca2+ channels mediate excitatory and inhibitory synaptic transmitter release in crayfish muscle.

PubMed

Araque, A; Clarac, F; Buño, W

1994-05-10

The toxin fraction (FTX) and peptide omega-Aga-IVA from the venom of the funnel-web spider Agelenopsis aperta, as well as a synthetic analogue of FTX, specifically block the P-type voltage-dependent Ca2+ channel (VDCC). The effects of these toxins on synaptic transmission were studied in the neuromuscular synapses of the crayfish opener muscle, which has a single excitatory and a single inhibitory motoneuron. FTX selectively and reversibly blocked excitatory and inhibitory postsynaptic currents and potentials in a dose-dependent manner. FTX had no effect on (i) resting and postsynaptic membrane conductance, (ii) postsynaptic L-type VDCC, and (iii) both glutamate- and gamma-aminobutyric acid-induced postsynaptic responses. Mean amplitude and frequency of miniature postsynaptic potentials were unchanged by FTX. The postsynaptic VDCC was inhibited by nifedipine, a selective dihydropyridine antagonist of L-type VDCC, whereas synaptic transmission was unaffected. Transmission was also undisturbed by omega-conotoxin, suggesting that N-type VDCCs are not involved. The peptide omega-Aga-IVA blocked excitatory and inhibitory transmission without affecting postsynaptic VDCC. Synaptic transmission was also blocked by synthetic FTX. We conclude that presynaptic P-type VDCCs are involved in both evoked excitatory and inhibitory transmitter release in crayfish neuromuscular synapses.

P-type Ca2+ channels mediate excitatory and inhibitory synaptic transmitter release in crayfish muscle.

PubMed Central

Araque, A; Clarac, F; Buño, W

1994-01-01

The toxin fraction (FTX) and peptide omega-Aga-IVA from the venom of the funnel-web spider Agelenopsis aperta, as well as a synthetic analogue of FTX, specifically block the P-type voltage-dependent Ca2+ channel (VDCC). The effects of these toxins on synaptic transmission were studied in the neuromuscular synapses of the crayfish opener muscle, which has a single excitatory and a single inhibitory motoneuron. FTX selectively and reversibly blocked excitatory and inhibitory postsynaptic currents and potentials in a dose-dependent manner. FTX had no effect on (i) resting and postsynaptic membrane conductance, (ii) postsynaptic L-type VDCC, and (iii) both glutamate- and gamma-aminobutyric acid-induced postsynaptic responses. Mean amplitude and frequency of miniature postsynaptic potentials were unchanged by FTX. The postsynaptic VDCC was inhibited by nifedipine, a selective dihydropyridine antagonist of L-type VDCC, whereas synaptic transmission was unaffected. Transmission was also undisturbed by omega-conotoxin, suggesting that N-type VDCCs are not involved. The peptide omega-Aga-IVA blocked excitatory and inhibitory transmission without affecting postsynaptic VDCC. Synaptic transmission was also blocked by synthetic FTX. We conclude that presynaptic P-type VDCCs are involved in both evoked excitatory and inhibitory transmitter release in crayfish neuromuscular synapses. Images PMID:7910404

Polymorphism of a widely used building block for halogen-bonded assemblies: 1,3,5-trifluoro-2,4,6-triiodobenzene.

PubMed

Raffo, Pablo A; Suárez, Sebastián; Fantoni, Adolfo C; Baggio, Ricardo; Cukiernik, Fabio D

2017-09-01

After reporting the structure of a new polymorph of 1,3,5-trifluoro-2,4,6-triiodobenzene (denoted BzF3I3), C 6 F 3 I 3 , (I), which crystallized in the space group P2 1 /c, we perform a comparative analysis with the already reported P2 1 /n polymorph, (II) [Reddy et al. (2006). Chem. Eur. J. 12, 2222-2234]. In polymorph (II), type-II I...I halogen bonds and I...π interactions connect molecules in such a way that a three-dimensional structure is formed; however, the way in which molecules are connected in polymorph (I), through type-II I...I halogen bonds and π-π interactions, gives rise to an exfoldable lamellar structure, which looks less tightly bound than that of (II). In agreement with this structural observation, both the melting point and the melting enthalpy of (I) are lower than those of (II).

Stabilized phosphogypsum: class C fly ash: Portland type II cement composites for potential marine application.

PubMed

Guo, T; Malone, R F; Rusch, K A

2001-10-01

Phosphogypsum (PG, CaSO4 x H20), a byproduct of phosphoric acid manufacturing, contains low levels of Ra226. PG can be stabilized with portland type II cement and class C fly ash for use in marine environments, thus eliminating the airborne vector of transmission for radon gas. An augmented simplex centroid design with pseudocomponents was used to select 10 PG:class C fly ash:portland type II cement compositions. The 43 cm3 blocks were fabricated and subjected to a 1.5-yr field submergence test and a 28-d saltwater dynamic leaching study. All field composites survived with no signs of degradation. Dynamic leaching resulted in effective calcium diffusion coefficients ranging from 0.21 to 7.5 x 10(-14)m2 s(-1). Effective diffusion depths, calculated for t=1 and 30 yr, ranged from 0.4 to 2.2 mm and from 2.0 to 11.9 mm, respectively. Scanning electron microscopy and wavelength dispersive microprobe and X-ray diffraction analyses of the leached composites identified a 40-60-microm calcite layer that was absent in the control composites. This suggests that a reaction between the composites and the saltwater results in the precipitation of calcite onto the block surface, encapsulating the composites and protecting them from saltwater attack and dissolution.

Quantal and Nonquantal Transmission in Calyx-Bearing Fibers of the Turtle Posterior Crista

PubMed Central

Holt, Joseph C.; Chatlani, Shilpa; Lysakowski, Anna; Goldberg, Jay M.

2010-01-01

Intracellular recordings were made from nerve fibers in the posterior ampullary nerve near the neuroepithelium. Calyx-bearing afferents were identified by their distinctive efferent-mediated responses. Such fibers receive inputs from both type I and type II hair cells. Type II inputs are made by synapses on the outer face of the calyx ending and on the boutons of dimorphic fibers. Quantal activity, consisting of brief mEPSPs, is reduced by lowering the external concentration of Ca2+ and blocked by the AMPA-receptor antagonist CNQX. Poisson statistics govern the timing of mEPSPs, which occur at high rates (250–2,500/s) in the absence of mechanical stimulation. Excitation produced by canal-duct indentation can increase mEPSP rates to nearly 5,000/s. As the rate increases, mEPSPs can change from a monophasic depolarization to a biphasic depolarizing– hyperpolarizing sequence, both of whose components are blocked by CNQX. Blockers of voltage-gated currents affect mEPSP size, which is decreased by TTX and is increased by linopirdine. mEPSP size decreases several fold after impalement. The size decrease, although it may be triggered by the depolarization occurring during impalement, persists even at hyperpolarized membrane potentials. Nonquantal transmission is indicated by shot-noise calculations and by the presence of voltage modulations after quantal activity is abolished pharmacologically. An ultrastructural study shows that inner-face inputs from type I hair cells outnumber outer-face inputs from type II hair cells by an almost 6:1 ratio. PMID:17596419

Quality of selected coal seams from Indiana: Implications for carbonization

USGS Publications Warehouse

Walker, R.; Mastalerz, Maria; Padgett, P.

2001-01-01

The chemical properties of two high-volatile bituminous coals, the Danville Coal Member of the Dugger Formation and the Lower Block Coal Member of the Brazil Formation from southern Indiana, were compared to understand the differences in their coking behavior. It was determined that of the two, the Lower Block has better characteristics for coking. Observed factors that contribute to the differences in the coking behavior of the coals include carbon content, organic sulfur content, and oxygen/carbon (O/C) ratios. The Lower Block coal has greater carbon content than the Danville coal, leading to a lower O/C ratio, which is more favorable for coking. Organic sulfur content is higher in the Lower Block coal, and a strong correlation was found between organic sulfur and plasticity. The majority of the data for both seams plot in the Type III zone on a van Krevelen diagram, and several samples from the Lower Block coal plot into the Type II zone, suggesting a perhydrous character for those samples. This divergence in properties between the Lower Block and Danville coals may account for the superior coking behavior of the Lower Block coal. ?? 2001 Elsevier Science B.V. All rights reserved.

Characterizing the inverses of block tridiagonal, block Toeplitz matrices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boffi, Nicholas M.; Hill, Judith C.; Reuter, Matthew G.

2014-12-04

We consider the inversion of block tridiagonal, block Toeplitz matrices and comment on the behaviour of these inverses as one moves away from the diagonal. Using matrix M bius transformations, we first present an O(1) representation (with respect to the number of block rows and block columns) for the inverse matrix and subsequently use this representation to characterize the inverse matrix. There are four symmetry-distinct cases where the blocks of the inverse matrix (i) decay to zero on both sides of the diagonal, (ii) oscillate on both sides, (iii) decay on one side and oscillate on the other and (iv)more » decay on one side and grow on the other. This characterization exposes the necessary conditions for the inverse matrix to be numerically banded and may also aid in the design of preconditioners and fast algorithms. Finally, we present numerical examples of these matrix types.« less

Angiotensin receptor blockers: Focus on cardiac and renal injury.

PubMed

Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Krishnamurthy, Prasanna; Suzuki, Kenji; Nakamura, Masahiko; Watanabe, Kenichi

2016-04-01

Angiotensin II, an important component of renin angiotensin system, is a potent vasopressor and its actions are mostly mediated via angiotensin II type 1 receptor (AT1R) and role of AT2R in counterbalancing the actions of AT1R stimulation are under extensive research. In addition to its physiological actions, angiotensin II plays important roles in the pathogenesis of atherosclerosis, hypertension, left ventricular hypertrophy, and heart failure. The effects of angiotensin II can be blocked by either suppressing its production by blocking angiotensin converting enzyme or by antagonizing its actions on AT1R using angiotensin II receptor blockers (ARBs). Instead of the extensive use of ARBs in the treatment of various cardiovascular diseases, proper selection of a particular ARB is crucial as the clinical condition of individual patient is different and also their economic status would play an essential role in medication compliance. Thus a critical review of the proven and promising actions of ARBs against various pathological conditions will be of great importance for the clinicians as well as for the researchers. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of pectoral nerve block versus thoracic paravertebral block for postoperative analgesia after radical mastectomy: a randomized controlled trial.

PubMed

Kulhari, S; Bharti, N; Bala, I; Arora, S; Singh, G

2016-09-01

Pectoral nerve (PecS) block is a recently introduced technique for providing surgical anaesthesia and postoperative analgesia during breast surgery. The present study was planned to compare the efficacy and safety of ultrasound-guided PecS II block with thoracic paravertebral block (TPVB) for postoperative analgesia after modified radical mastectomy. Forty adult female patients undergoing radical mastectomy were randomly allocated into two groups. Group 1 patients received a TPVB with ropivacaine 0.5%, 25 ml, whereas Group 2 patents received a PecS II block using same volume of ropivacaine 0.5% before induction of anaesthesia. Patient-controlled morphine analgesia was used for postoperative pain relief. The duration of analgesia was significantly prolonged in patients receiving the PecS II block compared with TPVB [mean (sd), 294.5 (52.76) vs 197.5 (31.35) min in the PecS II and TPVB group, respectively; P<0.0001]. The 24 h morphine consumption was also less in the PecS II block group [mean (sd), 3.90 (0.79) vs 5.30 (0.98) mg in PecS II and TPVB group, respectively; P<0.0001]. Postoperative pain scores were lower in the PecS II group compared with the TVPB group in the initial 2 h after surgery [median (IQR), 2 (2-2.5) vs 4 (3-4) in the Pecs II and TPVB group, respectively; P<0.0001]. Seventeen patients in the PecS II block group had T2 dermatomal spread compared with four patients in the TPVB group (P<0.001). No block-related complication was recorded. We found that the PecS II block provided superior postoperative analgesia than the TPVB in patients undergoing modified radical mastectomy without causing any adverse effect. CTRI/2014/06/004692. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increased photosystem II stability promotes H2 production in sulfur-deprived Chlamydomonas reinhardtii

PubMed Central

Volgusheva, Alena; Styring, Stenbjörn; Mamedov, Fikret

2013-01-01

Photobiological H2 production is an attractive option for renewable solar fuels. Sulfur-deprived cells of Chlamydomonas reinhardtii have been shown to produce hydrogen with the highest efficiency among photobiological systems. We have investigated the photosynthetic reactions during sulfur deprivation and H2 production in the wild-type and state transition mutant 6 (Stm6) mutant of Chlamydomonas reinhardtii. The incubation period (130 h) was dissected into different phases, and changes in the amount and functional status of photosystem II (PSII) were investigated in vivo by electron paramagnetic resonance spectroscopy and variable fluorescence measurements. In the wild type it was found that the amount of PSII is decreased to 25% of the original level; the electron transport from PSII was completely blocked during the anaerobic phase preceding H2 formation. This block was released during the H2 production phase, indicating that the hydrogenase withdraws electrons from the plastoquinone pool. This partly removes the block in PSII electron transport, thereby permitting electron flow from water oxidation to hydrogenase. In the Stm6 mutant, which has higher respiration and H2 evolution than the wild type, PSII was analogously but much less affected. The addition of the PSII inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea revealed that ∼80% of the H2 production was inhibited in both strains. We conclude that (i) at least in the earlier stages, most of the electrons delivered to the hydrogenase originate from water oxidation by PSII, (ii) a faster onset of anaerobiosis preserves PSII from irreversible photoinhibition, and (iii) mutants with enhanced respiratory activity should be considered for better photobiological H2 production. PMID:23589846

The Comparative Efficiency of Four Types of Endodontic Files and Reamers.

DTIC Science & Technology

1981-12-29

an reveree aide Ii neceeary end Identify by block number) Comparative efficiency of endodontic files; endodontic instrumentation ; instrumentation ...sections of bovine bone. Each canal was instrumented to a size 80 using four types of endodontic instruments : Hedstrom S files; K-files; reamers; and the...bovine bone. Each canal was instrumented to a size 80 using four types of endodontic instruments : Hedstrom files; K-files; reamers; and the new Unifile

Long-term blockade of L/N-type Ca2+ channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart

PubMed Central

Takahara, A; Nakamura, Y; Wagatsuma, H; Aritomi, S; Nakayama, A; Satoh, Y; Akie, Y; Sugiyama, A

2009-01-01

Background and purpose: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death. Experimental approach: The L-type Ca2+ channel blocker amlodipine (2.5 mg·day−1), L/N-type Ca2+ channel blocker cilnidipine (5 mg·day−1), or the angiotensin II receptor blocker candesartan (12 mg·day−1) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration. Key results: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat-to-beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed. Conclusions and implications: Long-term blockade of L/N-type Ca2+ channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases. PMID:19785655

AIM-9X Block II Sidewinder (AIM-9X Blk II)

DTIC Science & Technology

2015-12-01

Selected Acquisition Report (SAR) RCS: DD- A &T(Q& A )823-442 AIM-9X Block II Sidewinder (AIM-9X Blk II) As of FY 2017 President’s Budget Defense...MDAP - Major Defense Acquisition Program MILCON - Military Construction N/ A - Not Applicable O&M - Operations and Maintenance ORD - Operational...15:14:10 UNCLASSIFIED 5 Mission and Description The AIM-9X Block II Sidewinder (AIM-9X Blk II) short-range air-to-air missile is a long term

Continuous PECS II block for postoperative analgesia in patients undergoing transapical transcatheter aortic valve implantation.

PubMed

Shakuo, Tomoharu; Kakumoto, Shinichi; Kuribayashi, Junya; Oe, Katsunori; Seo, Katsuhiro

2017-01-01

It has been reported that PECS II block can alleviate postoperative pain following transapical transcatheter aortic valve implantation (TA-TAVI). However, the effectiveness of continuous PECS II block with catheterization has not yet been reported on the postoperative pain in patients undergoing TA-TAVI. We experienced two cases of TA-TAVI who received PECS II block with catheterization to manage postoperative pain. In the first case, a bolus injection for intraoperative pain and subsequent catheterization were performed before the implantation. However, the patient developed severe pain postoperatively in spite of the continuous block due to displacement of the catheter. In the second case, a bolus injection and the catheterization for the continuous block were performed before and after the implantation, respectively, which provided high-quality pain control. Continuous PECS II block may be useful to control perioperative pain associated with TA-TAVI. The insertion of the catheter after the implantation could be useful to avoid its displacement during the surgery.

Suture anchor fixation strength with or without augmentation in osteopenic and severely osteoporotic bones in rotator cuff repair: a biomechanical study on polyurethane foam model.

PubMed

Er, Mehmet Serhan; Altinel, Levent; Eroglu, Mehmet; Verim, Ozgur; Demir, Teyfik; Atmaca, Halil

2014-08-22

The purpose of the present study was to compare the results of various types of anchor applications with or without augmentation in both osteopenic and severely osteoporotic bone models. Two different types of suture anchors were tested in severely osteoporotic (SOP) and osteopenic polyurethane (PU) foam blocks using an established protocol. An Instron machine applied static loading parallel to the axis of insertion until failure, and the mean anchor failure strengths were calculated. The mode of failure (anchor pullout, suture tear) was recorded. The anchors tested included the Corkscrew (CS) (Arthrex Inc., Naples, FL, USA) (without augmentation, polymethylmethacrylate (PMMA)-augmented, and bioabsorbable tricalcium phosphate (TCP) cement-augmented) and Corkscrew FT II (CS FT II) 5.5 mm (without augmentation as used routinely). The mean failure loads for both SOP and osteopenic PU foam blocks, respectively, were as follows: CS, 16.2 and 212.4 N; CS with TCP, 75.2 and 396 N; CS with PMMA, 101.2 and 528.8 N; CS FT II, 13.8 and 339.8 N. Augmentation of CS with TCP or PMMA would be essential to SOP bones. In the osteopenic bone model, although anchor fixation augmented with PMMA is the best fixation method, CS augmented with TCP cement or CS FT II without any need for augmentation may also be used as an alternative.

Effects of brefeldin A on oligosaccharide processing. Evidence for decreased branching of complex-type glycans and increased formation of hybrid-type glycans.

PubMed

Chawla, D; Hughes, R C

1991-10-01

Brefeldin A (BFA), a drug that induces redistribution of Golgi-apparatus proteins into the endoplasmic reticulum, was used to determine the role of subcellular compartmentalization in the processing of asparagine-linked oligosaccharides. Baby-hamster kidney cells were pulse-labelled with [3H]mannose for 30-60 min and chased for up to several hours in the presence or in the absence of BFA or labelled continuously for several hours with and without the drug. Cellular glycoproteins were digested to glycopeptides with Pronase and either fractionated into glycan classes by lectin affinity chromatography or digested further by endoglycosidase H and endoglycosidase D. Released oligosaccharides obtained in the latter procedure were then separated from each other and from endoglycosidase-resistant glycopeptides by paper chromatography. The results show that BFA induces a very fast processing of protein-linked Glc3Man9GlcNAc2 oligosaccharide down to man5GlcNAc2 and conversion into complex-type and hybrid-type glycans. The major difference between untreated and BFA-treated cells is a large increase in bi-antennary and hybrid-type glycans in the latter cells. These results indicate that galactosylation of a mono-antennary GlcNAcMan5GlcNAc2 hybrid blocks subsequent action by mannosidase II and N-acetylglucosaminyl transferase II, producing galactosylated hybrid-type glycans. Similarly, galactosylation of the product of N-acetylglucosaminyltransferases I and II, i.e. a Man3GlcNAc2 core substituted with GlcNAc beta 1----2 on both alpha 1----3- and alpha 1----6-linked mannose residues, blocks branching N-acetylglucosaminyltransferases IV and V, thereby causing an increase in bi-antennary glycans and a decrease in tri- and tetra-antennary glycans.

Sub-seafloor acoustic characterization of seamounts near the Ogasawara Fracture Zone in the western Pacific using chirp (3-7 kHz) subbottom profiles

USGS Publications Warehouse

Lee, T.-G.; Hein, J.R.; Lee, Kenneth; Moon, J.-W.; Ko, Y.-T.

2005-01-01

A detailed analysis of chirp (3-7 kHz) subbottom profiles and bathymetry was performed on data collected from seamounts near the Ogasawara Fracture Zone (OFZ) in the western Pacific. The OFZ, which is a 150 km wide rift zone showing 600 km of right-lateral movement in a NW-SE direction, is unique among the fracture zones of the Pacific in that it includes many old seamounts (e.g., Magellan Seamounts and seamounts on Dutton Ridge). Sub-seafloor acoustic echoes on the seamounts are classified into nine specific types based on the nature and continuity of the echoes, subbottom structure, and morphology of the seafloor: (1) distinct echoes (types I-1, I-2, I-3), (2) indistinct echoes (types II-1, II-2, II-3), and (3) hyperbolic echoes (types III-1, III-2, III-3). Type I-2 pelagic sediments, characterized by thin and intermittent coverage, were probably deposited in topographically sheltered areas when bottom currents were strong, whereas type I-1 pelagic sediments accumulated during continuous and widespread sedimentation. Development of seamount flank rift zones in the OFZ may have been influenced by preexisting structures in the transform fracture zone at the time of volcanism, whereas those on Ita Mai Tai seamount in the Pigafetta Basin originated solely by edifice-building processes. Flank rift zones that formed by dike intrusions and eruptions played an important role in mass wasting. Mass-wasting processes included block faulting or block slides around the summit margin, sliding/slumping, debris flows, and turbidites, which may have been triggered by faulting, volcanism, dike injection, and weathering during various stages in the evolution of the seamounts. ?? 2005 Elsevier Ltd. All rights reserved.

Invasion of Epithelial Cells and Proteolysis of Cellular Focal Adhesion Components by Distinct Types of Porphyromonas gingivalis Fimbriae

PubMed Central

Nakagawa, Ichiro; Inaba, Hiroaki; Yamamura, Taihei; Kato, Takahiro; Kawai, Shinji; Ooshima, Takashi; Amano, Atsuo

2006-01-01

Porphyromonas gingivalis fimbriae are classified into six types (types I to V and Ib) based on the fimA genes encoding FimA (a subunit of fimbriae), and they play a critical role in bacterial interactions with host tissues. In this study, we compared the efficiencies of P. gingivalis strains with distinct types of fimbriae for invasion of epithelial cells and for degradation of cellular focal adhesion components, paxillin, and focal adhesion kinase (FAK). Six representative strains with the different types of fimbriae were tested, and P. gingivalis with type II fimbriae (type II P. gingivalis) adhered to and invaded epithelial cells at significantly greater levels than the other strains. There were negligible differences in gingipain activities among the six strains; however, type II P. gingivalis apparently degraded intracellular paxillin in association with a loss of phosphorylation 30 min after infection. Degradation was blocked with cytochalasin D or in mutants with fimA disrupted. Paxillin was degraded by the mutant with Lys-gingipain disrupted, and this degradation was prevented by inhibition of Arg-gingipain activity by Nα-p-tosyl-l-lysine chloromethyl ketone. FAK was also degraded by type II P. gingivalis. Cellular focal adhesions with green fluorescent protein-paxillin macroaggregates were clearly destroyed, and this was associated with cellular morphological changes and microtubule disassembly. In an in vitro wound closure assay, type II P. gingivalis significantly inhibited cellular migration and proliferation compared to the cellular migration and proliferation observed with the other types. These results suggest that type II P. gingivalis efficiently invades epithelial cells and degrades focal adhesion components with Arg-gingipain, which results in cellular impairment during wound healing and periodontal tissue regeneration. PMID:16790749

HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis

PubMed Central

Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

2016-01-01

Introduction Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. Aim To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. Materials and Methods A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Statistical Analysis Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). Results HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). Conclusion The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The stepwise increase in H- score of GLUT-1 in the studied cases implies its potential role in carcinogenesis of EC. HIF-1α may promote GLUT-1 expression in EC especially surrounding areas of necrosis. The differences between type I and type II EC regarding HIF-1α and GLUT-1 expression may confirm the differences in their aetiopathogenesis. PMID:27437226

HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis.

PubMed

Al-Sharaky, Dalia Rifaat; Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

2016-05-01

Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The stepwise increase in H- score of GLUT-1 in the studied cases implies its potential role in carcinogenesis of EC. HIF-1α may promote GLUT-1 expression in EC especially surrounding areas of necrosis. The differences between type I and type II EC regarding HIF-1α and GLUT-1 expression may confirm the differences in their aetiopathogenesis.

Cutting work in thick section cryomicrotomy.

PubMed

Saubermann, A J; Riley, W D; Beeuwkes, R

1977-09-01

The forces during cryosectioning were measured using miniature strain gauges attached to a load cell fitted to the drive arm of the Porter-Blum MT-2 cryomicrotome. Work was calculated and the data normalized to a standard (1 mm X 1 mm X 0.5 micrometer) section. Thermal energy generated was also calculated. Five parameters were studied: cutting angle, thickness, temperature, hardness, and block shape. Force patterns could be divided into three major groups thought to represent cutting (Type I), large fracture planes greater than 10 micrometer in length (Type II), and small fracture planes less than 10 micrometer in length (Type III). Type I and Type II produced satisfactory sections. Work in cutting ranged from an average of 78.4 muJ to 568.8 muJ. Cutting angle and temperature had the greatest effect on sectioning. Heat generated would be sufficient to cause through-section melting for 0.5 micrometer thick sections assuming the worst possible case, namely that all heat went into the section without loss. Presence of a Type II pattern (large fracture pattern) is thought to be presumptive evidence against thawing.

Proteolytic activities in yeast after UV irradiation. II. Variation in proteinase levels in mutants blocked in DNA-repair pathways.

PubMed

Schwencke, J; Moustacchi, E

1982-01-01

When the levels of three common yeast proteinases in exponentially growing cells of mutants blocked in different repair pathways are compared to that of isogenic wild-type cells, it can be seen that the level of proteinase B is enhanced in the mutants whereas the levels of leucin aminopeptidase (Leu.AP) and lysine aminopeptidase (Lys.AP) are similar in all strains. As in its corresponding wild type, the level of proteinase B activity is further enhanced after UV-irradiation in a mutant blocked in excision-repair (rad1-3). In contrast, following the same treatment the level of proteinase B remains almost constant in a mutant blocked in a general error-prone repair system (rad6-1) and in a mutant defective in a more specific mutagenic repair pathway (pso2-1). Cycloheximide, an inhibitor of protein synthesis, blocks the post-UV enhancement in proteinase B activity observed in rad1-3 indicating that, as in the wild-type cells, an inducible process is involved. The levels of Lys.AP and Leu.AP are, respectively, either unaffected or only moderately increased following UV-treatment of the repair defective mutants, as in wild-type strains. It is obvious that the induction of protease B activity following UV-treatment in Saccharomyces cannot be equated to the induction of the recA protein in Escherichia coli. However the correlation found between the block in mutagenic repair and the lack of UV-induction of protease B activity leads to questions on the possible role of certain protease activities in mutagenic repair in eucaryotic cells.

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

PubMed Central

2012-01-01

Background Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. Method In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Results Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Conclusion Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia. PMID:22214516

A Cephalometric Comparison of Twin Block and Bionator Appliances in Treatment of Class II Malocclusion

PubMed Central

Ahmadian-Babaki, Fatemeh; Araghbidi-Kashani, S. Mehdi

2017-01-01

Background Class II malocclusion is one of the most common orthodontic problems. In cases of class II malocclusion with mandibular deficiency, functional appliances often are used with the intent of stimulating mandibular growth. Bionator and twin block are two of the more popular functional appliances. The aim of this study was to compare the treatment outcomes of these two appliances using cephalometric radiographs. Material and Methods Cephalometric radiographs of 33 patients who had class II division I malocclusion, before and after treatment were digitalized. The mean changes in twin block and bionator groups were compared using independent t test. Results Twin block and bionator showed no statistically significant differences in cephalometric parameters except for ANB, NA-Pog, Basal and Ar-Go-Me angles. Conclusions There were no statistically significant differences in dentoalveolar and mandibular position between twin block and bionator (p>0.1). Twin block was more efficient in inhibition of forward movement of maxilla (p<0.1). Key words:Functional, Class II malocclusion, Cephalometrics, Twin block, Bionator, Treatment. PMID:28149473

Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats

PubMed Central

Johnson, Philip L; Fitz, Stephanie D; Engleman, Eric A; Svensson, Kjell A; Schkeryantz, Jeffrey M; Shekhar, Anantha

2015-01-01

Rats with chronic inhibition of GABA synthesis by infusion of l-allyglycine, a glutamic acid decarboxylase inhibitor, into their dorsomedial/perifornical hypothalamus are anxious and exhibit panic-like cardio-respiratory responses to treatment with intravenous (i.v.) sodium lactate (NaLac) infusions, in a manner similar to what occurs in patients with panic disorder. We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2/3 receptor agonists can block such a NaLac response, suggesting that a glutamate mechanism is contributing to this panic-like state. Using this animal model of panic, we tested the efficacy of CBiPES and THIIC, which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators (at 10–30mg/kg i.p.), in preventing NaLac-induced panic-like behavioral and cardiovascular responses. The positive control was alprazolam (3mg/kg i.p.), a clinically effective anti-panic benzodiazepine. As predicted, panic-prone rats given a NaLac challenge displayed NaLac-induced panic-like cardiovascular (i.e. tachycardia and hypertensive) responses and “anxiety” (i.e. decreased social interaction time) and “flight” (i.e. increased locomotion) -associated behaviors; however, systemic injection of the panic-prone rats with CBiPES, THIIC or alprazolam prior to the NaLac dose blocked all NaLac-induced panic-like behaviors and cardiovascular responses. These data suggested that in a rat animal model, selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti-panic efficacy similar to alprazolam. PMID:22914798

Continuous Ilioinguinal-iliohypogastric Nerve Block for Groin Pain in a Breast-feeding Patient after Cesarean Delivery.

PubMed

Kim, Eun Soo; Kim, Hae Kyu; Baik, Ji Seok; Ji, Young Tae

2016-07-01

Ilioinguinal and iliohypogastric (II/IH) nerve injury is one of the most common nerve injuries following pelvic surgery, especially with the Pfannenstiel incision. We present a case of intractable groin pain, successfully treated with a continuous II/IH nerve block. A 33-year-old woman, following emergency cesarean section due to cephalopelvic disproportion, presented numbness in left inguinal area and severe pain on the labia on the second postoperative day. The pain was burning, lancinating, and exacerbated by standing or movement. However, she didn't want to take additional medicine because of breast-feeding. A diagnostic II/IH nerve block produced a substantial decrease in pain. She underwent a continuous II/IH nerve block with a complete resolution of pain within 3 days. A continuous II/IH nerve block might be a goodoption for II/IH neuropathy with intractable groin pain in breast-feeding mothers without adverse drug reactions in their infants.

Surface Charge Transfer Doping via Transition Metal Oxides for Efficient p-Type Doping of II-VI Nanostructures.

PubMed

Xia, Feifei; Shao, Zhibin; He, Yuanyuan; Wang, Rongbin; Wu, Xiaofeng; Jiang, Tianhao; Duhm, Steffen; Zhao, Jianwei; Lee, Shuit-Tong; Jie, Jiansheng

2016-11-22

Wide band gap II-VI nanostructures are important building blocks for new-generation electronic and optoelectronic devices. However, the difficulty of realizing p-type conductivity in these materials via conventional doping methods has severely handicapped the fabrication of p-n homojunctions and complementary circuits, which are the fundamental components for high-performance devices. Herein, by using first-principles density functional theory calculations, we demonstrated a simple yet efficient way to achieve controlled p-type doping on II-VI nanostructures via surface charge transfer doping (SCTD) using high work function transition metal oxides such as MoO 3 , WO 3 , CrO 3 , and V 2 O 5 as dopants. Our calculations revealed that these oxides were capable of drawing electrons from II-VI nanostructures, leading to accumulation of positive charges (holes injection) in the II-VI nanostructures. As a result, Fermi levels of the II-VI nanostructures were shifted toward the valence band regions after surface modifications, along with the large enhancement of work functions. In situ ultraviolet photoelectron spectroscopy and X-ray photoelectron spectroscopy characterizations verified the significant interfacial charge transfer between II-VI nanostructures and surface dopants. Both theoretical calculations and electrical transfer measurements on the II-VI nanostructure-based field-effect transistors clearly showed the p-type conductivity of the nanostructures after surface modifications. Strikingly, II-VI nanowires could undergo semiconductor-to-metal transition by further increasing the SCTD level. SCTD offers the possibility to create a variety of electronic and optoelectronic devices from the II-VI nanostructures via realization of complementary doping.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Amino acid residues involved in membrane insertion and pore formation of Clostridium botulinum C2 toxin.

PubMed

Lang, Alexander E; Neumeyer, Tobias; Sun, Jianjun; Collier, R John; Benz, Roland; Aktories, Klaus

2008-08-12

The actin-ADP-ribosylating Clostridium botulinum C2 toxin consists of the enzymatic component C2I and the binding component C2II. C2II forms heptameric channels involved in translocation of the enzymatic component into the target cell. On the basis of the heptameric toxin channel, we studied functional consequences of mutagenesis of amino acid residues probably lining the lumen of the toxin channel. Substitution of glutamate-399 of C2II with alanine blocked channel formation and cytotoxicity of the holotoxin. Although cytotoxicity and rounding up of cells by C2I were completely blocked by exchange of phenylalanine-428 with alanine, the mutation increased potassium conductance caused by C2II in artificial membranes by about 2-3-fold over that of wild-type toxin. In contrast to its effects on single-channel potassium conductance in artificial membranes, the F428A mutation delayed the kinetics of pore formation in lipid vesicles and inhibited the activity of C2II in promoting (86)Rb (+) release from preloaded intact cells after pH shift of the medium. Moreover, F428A C2II exhibited delayed and diminished formation of C2II aggregates at low pH, indicating major changes of the biophysical properties of the toxin. The data indicate that phenylalanine-428 of C2II plays a major role in conformational changes occurring during pore formation of the binding component of C2II.

Measurement Space Drill Support

DTIC Science & Technology

2015-08-30

II) H-47 Block II (I) *H-47 Block II (II) AVN FVL Att (I) * AVN FVL Att (II) TRAC- MTRY F2025B Logistic Flow MS Drill Support FY15 Research...does not have to use other AVN /ground assets to cover the area, freeing these assets to perform other missions and potentially enhancing the

Concentrating Solar Power Projects - Astexol II | Concentrating Solar Power

Science.gov Websites

(Badajoz) Owner(s): Elecnor/Aries/ABM AMRO (100%) Technology: Parabolic trough Turbine Capacity: Net: 50.0 Difference: 100°C Power Block Turbine Capacity (Gross): 50.0 MW Turbine Capacity (Net): 50.0 MW Output Type indirect Storage Capacity: 8 Hours Thermal Storage Description:

[Study on rules of TCM syndrome in patients with dyslipidemia and its objectization].

PubMed

Lei, Yan; Wang, Zhen-Hua; Liu, Jian-Gang

2007-12-01

To explore the rules of TCM syndrome in patients with dyslipidemia and its relation with C-reactive protein (CRP), homocysteine (Hcy), carotid ultrasonic picture, blood lipids and blood viscosity. From 152 recruited patients symptoms and physical signs (including figures of tongue and pulse) were selected and analyzed in grading and quantifying by factor analysis. At the same time, blood lipids, CRP, Hcy, carotid ultrasonic picture and blood viscosity were detected to conduct a canonical correlation analysis for exploring the relationship between different TCM syndromes and their corresponding physical and/or chemical indexes. Five types of TCM syndrome obtained by factor analysis were syndrome of Shen-yin deficiency (I), Pi-qi deficiency (II), turbid-phlegm impediment (III), blood stasis (IV), and phlegm-blood block (V). By canonical correlation analysis, they were characterized with: Type I, high levels of CRP and blood viscosity; Type II, high level of very low-density lipoprotein cholesterol (VLDL-C); Type III, high level of total cholesterol (TC) and low level of high-density lipoprotein cholesterol (HDL-C); and Type V, high level of Hcy. The five syndrome types frequently found in patients with dyslipidemia are syndrome of Shen-yin deficiency, Pi-qi deficiency, turbid-phlegm impediment, blood stasis, and phlegm-blood block. Different syndrome has its own correlation with some corresponding physical and/or chemical laboratory indexes, the issue provides new evidences for the objectification of TCM syndromes in patients with dyslipidemia.

Contractility in type III cochlear fibrocytes is dependent on non-muscle myosin II and intercellular gap junctional coupling.

PubMed

Kelly, John J; Forge, Andrew; Jagger, Daniel J

2012-08-01

The cochlear spiral ligament is a connective tissue that plays diverse roles in normal hearing. Spiral ligament fibrocytes are classified into functional sub-types that are proposed to carry out specialized roles in fluid homeostasis, the mediation of inflammatory responses to trauma, and the fine tuning of cochlear mechanics. We derived a secondary sub-culture from guinea pig spiral ligament, in which the cells expressed protein markers of type III or "tension" fibrocytes, including non-muscle myosin II (nmII), α-smooth muscle actin (αsma), vimentin, connexin43 (cx43), and aquaporin-1. The cells formed extensive stress fibers containing αsma, which were also associated intimately with nmII expression, and the cells displayed the mechanically contractile phenotype predicted by earlier modeling studies. cx43 immunofluorescence was evident within intercellular plaques, and the cells were coupled via dye-permeable gap junctions. Coupling was blocked by meclofenamic acid (MFA), an inhibitor of cx43-containing channels. The contraction of collagen lattice gels mediated by the cells could be prevented reversibly by blebbistatin, an inhibitor of nmII function. MFA also reduced the gel contraction, suggesting that intercellular coupling modulates contractility. The results demonstrate that these cells can impart nmII-dependent contractile force on a collagenous substrate, and support the hypothesis that type III fibrocytes regulate tension in the spiral ligament-basilar membrane complex, thereby determining auditory sensitivity.

Suture anchor fixation strength with or without augmentation in osteopenic and severely osteoporotic bones in rotator cuff repair: a biomechanical study on polyurethane foam model

PubMed Central

2014-01-01

Background The purpose of the present study was to compare the results of various types of anchor applications with or without augmentation in both osteopenic and severely osteoporotic bone models. Methods Two different types of suture anchors were tested in severely osteoporotic (SOP) and osteopenic polyurethane (PU) foam blocks using an established protocol. An Instron machine applied static loading parallel to the axis of insertion until failure, and the mean anchor failure strengths were calculated. The mode of failure (anchor pullout, suture tear) was recorded. The anchors tested included the Corkscrew® (CS) (Arthrex Inc., Naples, FL, USA) (without augmentation, polymethylmethacrylate (PMMA)-augmented, and bioabsorbable tricalcium phosphate (TCP) cement-augmented) and Corkscrew® FT II (CS FT II) 5.5 mm (without augmentation as used routinely). Results The mean failure loads for both SOP and osteopenic PU foam blocks, respectively, were as follows: CS, 16.2 and 212.4 N; CS with TCP, 75.2 and 396 N; CS with PMMA, 101.2 and 528.8 N; CS FT II, 13.8 and 339.8 N. Conclusions Augmentation of CS with TCP or PMMA would be essential to SOP bones. In the osteopenic bone model, although anchor fixation augmented with PMMA is the best fixation method, CS augmented with TCP cement or CS FT II without any need for augmentation may also be used as an alternative. PMID:25148925

PEP-1-SIRT2-induced matrix metalloproteinase-1 and -13 modulates type II collagen expression via ERK signaling in rabbit articular chondrocytes.

PubMed

Eo, Seong-Hui; Choi, Soo Young; Kim, Song Ja

2016-11-01

Matrix metalloproteinases (MMPs) are critical for the degradation of the extracellular matrix (ECM), which includes cartilage-specific collagen types I, II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce dedifferentiation of articular chondrocytes; however, the underlying mechanisms remains unclear. We addressed this in the present study by examining the association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by western blotting. A similar trend in MMP-1 and -13 levels was observed in cultures during expansion to four passages. Pharmacological inhibition of MMP-1 and -13 blocked the PEP-1-SIRT2-induced decrease in type II collagen level. Phosphorylation of extracellular regulated kinase (ERK) was increased by PEP-1-SIRT2; however, treatment with the mitogen-activated protein kinase inhibitor PD98059 suppressed PEP-1-SIRT2-induced MMP-1 and -13 expression and dedifferentiation while restoring type II collagen expression in passage 2 cells. These results suggest that PEP-1-SIRT2 promotes MMP-induced dedifferentiation via ERK signaling in articular chondrocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Characteristics of acetaminophen absorption in healthy unweaned calves as an indirect measurement of the oroduodenal transit rate of liquid meals.

PubMed

Schaer, S; Herrli-Gygi, M; Kosmeas, N; Boschung, H; Steiner, A

2005-09-01

Abomasal emptying plays an important role in the incidence of digestive problems in calves. Our aim was to evaluate the acetaminophen absorption test (APAT) for characterization of the oroduodenal transit (ODT) of liquid meals in unweaned calves. Six healthy, unweaned Simmental x Red Holstein crossbred calves were involved in the project. The study was performed in three blocks at 3, 6 and 9 weeks of the calves' age. Within blocks, APAT was performed twice at an interval of at least 24 h. Once per each block, liquid transit was carried out with non-coagulating electrolyte solution (NES). The second test within a block was performed either while atropine sulphate was administered (block I), or by feeding a coagulating milk replacer (block II), or by administration of NES by ruminal tube (block III). Data were compared within and among blocks. Significant differences of several APAT traits were present for the different types of feeding, the different types of meals, the administration of atropine sulphate and the different ages of the calves. The emptying index T(max)/C(max) was suggested to be a valuable kinetic parameter for the characterization of ODT in these calves. We conclude that APAT represents a valid technique for characterization of ODT of liquid meals in healthy unweaned calves and may be a valuable tool for the evaluation of the reticular groove mechanism, the abomasal emptying and the absorption capacity of the duodenum.

Protein kinase C βII and TGFβRII in ω-3 fatty acid–mediated inhibition of colon carcinogenesis

PubMed Central

Murray, Nicole R.; Weems, Capella; Chen, Lu; Leon, Jessica; Yu, Wangsheng; Davidson, Laurie A.; Jamieson, Lee; Chapkin, Robert S.; Thompson, E. Aubrey; Fields, Alan P.

2002-01-01

Încreasing evidence demonstrates that protein kinase C βII (PKCβII) promotes colon carcinogenesis. We previously reported that colonic PKCβII is induced during colon carcinogenesis in rodents and humans, and that elevated expression of PKCβII in the colon of transgenic mice enhances colon carcinogenesis. Here, we demonstrate that PKCβII represses transforming growth factor β receptor type II (TGFβRII) expression and reduces sensitivity to TGF-β–mediated growth inhibition in intestinal epithelial cells. Transgenic PKCβII mice exhibit hyperproliferation, enhanced colon carcinogenesis, and marked repression of TGFβRII expression. Chemopreventive dietary ω-3 fatty acids inhibit colonic PKCβII activity in vivo and block PKCβII-mediated hyperproliferation, enhanced carcinogenesis, and repression of TGFβRII expression in the colonic epithelium of transgenic PKCβII mice. These data indicate that dietary ω-3 fatty acids prevent colon cancer, at least in part, through inhibition of colonic PKCβII signaling and restoration of TGF-β responsiveness. PMID:12058013

Interactions of pyrethroid insecticides with GABA sub A and peripheral-type benzodiazepine receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devaud, L.L.

1988-01-01

Pyrethroid insecticides are potent proconvulsants in the rat. All pyrethroids evincing proconvulsant activity elicited a similar 25-30% maximal reduction of seizure threshold. The Type II pyrethroids were the most potent proconvulsants with 1R{alpha}S, cis cypermethrin having an ED{sub 50} value of 6.3 nmol/kg. The proconvulsant activity of both Type I and Type II pyrenthroids was blocked by pretreatment with PK 11195, the peripheral-type benzodiazepine receptor (PTBR) antagonist. In contrast, phenytoin did not antagonize the proconvulsant activity of either deltamethrin or permethrin. Pyrethroids displaced the specific binding of ({sup 3}H)Ro5-4864 to rat brain membranes with a significant correlation between the logmore » EC{sub 50} values for their activities as proconvulsants and the log IC{sub 50} values for their inhibition of ({sup 3}H)Ro5-4864 binding. Both Ro5-4864 and pyrethroid insecticides were found to influence specific ({sup 35}S)TBPS binding in a GABA-dependent manner. PK 11195 and the Type II pyrethroid, deltamethrin antagonized the Ro5-4864-induced modulation of ({sup 35}S)TBPS binding. Pyrethroid insecticides, Ro5-4864 and veratridine influenced GABA-gated {sup 36}Chloride influx. Moreover, the Type II pyrethroids elicited an increase in {sup 36}chloride influx in the absence of GABA-stimulation. Both of these actions were antagonized by PK 11195 and tetrodotoxin.« less

A Local DCT-II Feature Extraction Approach for Personal Identification Based on Palmprint

NASA Astrophysics Data System (ADS)

Choge, H. Kipsang; Oyama, Tadahiro; Karungaru, Stephen; Tsuge, Satoru; Fukumi, Minoru

Biometric applications based on the palmprint have recently attracted increased attention from various researchers. In this paper, a method is presented that differs from the commonly used global statistical and structural techniques by extracting and using local features instead. The middle palm area is extracted after preprocessing for rotation, position and illumination normalization. The segmented region of interest is then divided into blocks of either 8×8 or 16×16 pixels in size. The type-II Discrete Cosine Transform (DCT) is applied to transform the blocks into DCT space. A subset of coefficients that encode the low to medium frequency components is selected using the JPEG-style zigzag scanning method. Features from each block are subsequently concatenated into a compact feature vector and used in palmprint verification experiments with palmprints from the PolyU Palmprint Database. Results indicate that this approach achieves better results than many conventional transform-based methods, with an excellent recognition accuracy above 99% and an Equal Error Rate (EER) of less than 1.2% in palmprint verification.

DIVWAG Model Documentation. Volume II. Programmer/Analyst Manual. Part 5.

DTIC Science & Technology

1976-07-01

Words Number Mission type: I=DAFS; 2= CAS 1 8 Estimated X coordinate of target 1 9 Estimated Y coordinate of target 1 10 Reject code: 0-mission unit... CAS 1 8 Abort indicator: O-no abort; 1-abort 1 9 X coordinate of target 1 10 " :oordinate of target 1 11 Aircraft munitions item code 6 12-17 Aircraft...L300 CALL TRNSMT U. TO TRANSMIT FIRST BLOCK OF DATA L100 YES REQUEST FOR INPU? LIOI CA " TRAN21I TO TRANSMIT LAST BLOCK OF DATA Figure VII-3-B- 10

Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.

PubMed

Li, Tuoyi; Yu, Bing; Liu, Zhixin; Li, Jingyuan; Ma, Mingliang; Wang, Yingbao; Zhu, Mingjiang; Yin, Huiyong; Wang, Xiaofeng; Fu, Yi; Yu, Fang; Wang, Xian; Fang, Xiaohong; Sun, Jinpeng; Kong, Wei

2018-01-02

Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg 167 and Cys 289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.

Evidences for Skeletal Structures in the Ocean from the Images Analyzed by Multilevel Dynamical Contrasting Method

NASA Astrophysics Data System (ADS)

Rantsev-Kartinov, Valentin A.

2004-11-01

An analysis of databases of photographic images of ocean's surface, taken from various altitudes and for various types of rough ocean surface, revealed the presence of an ocean's skeletal structures (OSS) = http://www.arxiv.org/ftp/physics/papers/0401/0401139.pdf [1] Rantsev-Kartinov V.A., Preprint, which exhibit a tendency toward self-similarity of structuring at various length scales (i.e., within various ``generations''). The topology of the OSS appears to be identical to that of skeletal structures which have been formerly found in a wide range of length scales, media and for various phenomena (Phys. Lett. A, 2002, 306). The typical OSS consists of separate identical blocks which are linked together to form a network. Two types of such blocks are found: (i) a coaxial tubular (CT) structures with internal radial bonds, and (ii) a cartwheel-like structures, located either on an axle or in the edges of the CT blocks. The OSSs differ from the formerly found SSs only by the fact that OSS, in their interior, are filled in with closely packed OSSs of a smaller size. We specially discuss the phenomenon of skeletal blocks in the form of vertically/horizontally oriented floating cylinders. The size of these observed blocks is shown to grow with increasing rough water.

Prenatal Gender-Related Nicotine Exposure Increases Blood Pressure Response to Angiotensin II in Adult Offspring

PubMed Central

Xiao, DaLiao; Xu, Zhice; Huang, Xiaohui; Longo, Lawrence D.; Yang, Shumei; Zhang, Lubo

2008-01-01

Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month–old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II–stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring. In male offspring, nicotine exposure significantly increased Ang II–induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II–induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II–induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca2+ concentrations and Ca2+ sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor–mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring. PMID:18259024

Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian heart through a protein kinase C-dependent pathway.

PubMed

Kalra, Dinesh; Sivasubramanian, Natarajan; Mann, Douglas L

2002-05-07

Previous studies suggest that angiotensin II (Ang II) upregulates the expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the effect of Ang II on TNF expression in the adult mammalian heart is not known. To determine whether Ang II was sufficient to provoke TNF biosynthesis in the adult heart, we examined the effects of Ang II in isolated buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF mRNA and protein biosynthesis in the heart as well as in cultured adult cardiac myocytes. The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the activation of nuclear factor-kappaB and activator protein-1 (AP-1), two transcription factors that are important for TNF gene expression. Nuclear factor-kappaB activation was accompanied by phosphorylation of IkappaBalpha on serine 32 as well as degradation of IkappaBalpha, suggesting that the effects of Ang II were mediated through an IkappaBalpha-dependent pathway. The important role of protein kinase C (PKC) was suggested by studies in which a phorbol ester triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF biosynthesis. These studies suggest that Ang II provokes TNF biosynthesis in the adult mammalian heart through a PKC-dependent pathway.

Angiotensin II Reduces Food Intake by Altering Orexigenic Neuropeptide Expression in the Mouse Hypothalamus

PubMed Central

Yoshida, Tadashi; Semprun-Prieto, Laura; Wainford, Richard D.; Sukhanov, Sergiy; Kapusta, Daniel R.

2012-01-01

Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated. PMID:22234465

A comparative study to evaluate ultrasound-guided transversus abdominis plane block versus ilioinguinal iliohypogastric nerve block for post-operative analgesia in adult patients undergoing inguinal hernia repair.

PubMed

Kamal, Kirti; Jain, Parul; Bansal, Teena; Ahlawat, Geeta

2018-04-01

Both transversus abdominis plane (TAP) block and combined ilioinguinal-iliohypogastric (IIN/IHN) blocks are used routinely under ultrasound (USG) guidance for postoperative pain relief in patients undergoing inguinal hernia surgery. This study compares USG guided TAP Vs IIN/IHN block for post-operative analgesic efficacy in adults undergoing inguinal hernia surgery. Sixty adults aged 18 to 60 with American Society of Anesthesiologsts' grade I or II were included. After general anaesthesia, patients in Group I received USG guided unilateral TAP block using 0.75% ropivacaine 3 mg/kg (maximum 25 mL) and those in Group II received IIN/IHN block using 10 mL 0.75% ropivacaine. Postoperative rescue analgesia was with tramadol (intravenous) IV ± diclofenac IV in the first 4 h followed by oral diclofenac subsequently. Total analgesic consumption in the first 24 h was the primary objective, intraoperative haemodynamics, number of attempts and time required for performing the block as well as the postoperative pain scores were also evaluated. Time to first analgesic request was 319.8 ± 115.2 min in Group I and 408 ± 116.4 min in Group II ( P = 0.005). Seven patients (23.33%) in Group I and two (6.67%) in Group II required tramadol in first four hours. No patient in either groups received diclofenac IV. The average dose of tablet diclofenac was 200 ± 35.96 mg in Group I and 172.5 ± 34.96 mg in Group II ( P = 0. 004). USG guided IIN/IHN block reduces the postoperative analgesic requirement compared to USG guided TAP block.

Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons.

PubMed

Kostic, Sandra; Pan, Bin; Guo, Yuan; Yu, Hongwei; Sapunar, Damir; Kwok, Wai-Meng; Hudmon, Andy; Wu, Hsiang-En; Hogan, Quinn H

2014-09-01

Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca(2+) channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca(2+) currents in peripheral sensory neurons acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small molecule CaMKII inhibitor KN-93 (1.0μM) reduced depolarization-induced ICa by 16-30% in excess of the effects produced by the inactive homolog KN-92. The specificity of CaMKII inhibition on VGCC function was shown by the efficacy of the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in a membrane-permeable myristoylated form, which also reduced VGCC current in resting neurons. Loss of VGCC currents is primarily due to reduced N-type current, as application of mAIP selectively reduced N-type current by approximately 30%, and prior N-type current inhibition eliminated the effect of mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno-associated virus expressing AIP also resulted in a loss of N-type currents. Together, these findings reveal a novel molecular adaptation whereby sensory neurons retain CaMKII support of VGCCs despite remaining quiescent. Published by Elsevier Inc.

[My hybrid carrier of clinical pathologist].

PubMed

Honda, Takayuki

2011-03-01

In this review, I showed a brief summary of my carrier in multiple special fields (clinical pathologist, anatomical pathologist of lung, respiratory physician and infection control doctor), my studies and my own view of laboratory medicine. We chiefly study pathology of the lung, especially about type II pneumocytes. Type II pneumocytes had abundant surface coat on the apical surface containing a specific carbohydrate structure of Thomsen-Friedenreich (TF) antigen. TF antigen is a marker of type II pneumocytes beyond animal species, and can be used for evaluating activity of various interstitial pneumonia as type II pneumocyte index (number/lmm alveolar length). Three dimensional views generated from thick sections of ordinary processed paraffin blocks showed new information of normal and abnormal lung morphology. Type II pneumocytes linearly located along the elastic fibers forming framework of polygonal alveoli, and in usual interstitial pneumonia, destruction of these elastic fibers were observed. In Japan, roles of a clinical pathologist are not definite as a radiologist, and clinical laboratory in a hospital is recognized as a section only performing blood and chemical tests. Evaluation of the data and participation in diagnosis were not requested. In future, medical doctors devote themselves to treat patients, and clinical pathologists and laboratory technicians have to help the doctors in diagnostic process. Routine tests (blood and urine) are most frequently performed in clinical medicine, but the data are not adequately used. Therefore, a system is necessary for interpreting routine tests and reporting them to other medical staffs.

Electrocardiographic characteristics of atrioventricular block induced by tilt testing.

PubMed

Zyśko, Dorota; Gajek, Jacek; Koźluk, Edward; Mazurek, Walentyna

2009-02-01

The electrocardiographic (ECG) characteristics of atrioventricular (AV) block during reflex syncope may be unique due to the presence of hypervagotonia. The aim of the present study was to define the ECG characteristics of the AV block induced by neurocardiogenic reflex provoked by tilt testing (TT). A series of 31 patients with presumed vasovagal syncope and AV block provoked by TT was studied. The duration of PP and PR interval, AV block grade and type, concomitant arrhythmias, and timing of the AV block occurrence were assessed. The AV block occurred at TT termination in 26 patients, in the recovery in 4 patients, and in both periods in 1 patient. Atrioventricular block was preceded by sinus slowing, and sinus rhythm during AV block was slow and instable. Mobitz I, 2:1 second-degree AV block, and advanced second-degree AV block were recognized in 35.5, 48.4, and 67.8% of patients, respectively. Third-degree AV block was diagnosed in 41.9% of patients. Twenty-one patients had at least two AV block forms. The most prevalent concomitant arrhythmia was junctional escape rhythm (61.3%). (i) The occurrence of the AV block during neurocardiogenic reaction induced by TT is always preceded by sinus rhythm slowing and usually by PR interval prolongation. (ii) The AV block provoked by TT usually occurs at TT termination, but may occur even in the recovery period in a supine position. Sometimes the AV block may be present both at TT termination and during the recovery period.

Ba2F2Fe2+ 0.5Fe3+ S3: a two-dimensional inhomogeneous mixed valence iron compound.

PubMed

Kabbour, Houria; Cario, Laurent

2008-03-03

The structure of the new mixed valence compound Ba2F2Fe1.5S3 was solved by means of single crystal X-ray analysis. It crystallizes in an orthorhombic cell, in the Pnma space group with the cell parameters a = 12.528(3) A, b = 18.852(4) A, and c = 6.0896(12) A. The structure is formed by the alternated stacking of fluorite type [Ba2F2]2+ blocks and the newly discovered [Fe1.5S3]2- blocks. This [Fe1.5S3]2- block exhibits a mixed valence of iron with Fe(+II) located in octahedrons and Fe(+III) in tetrahedrons. Preliminary susceptibility measurements suggest a low dimensional antiferromagnetic behavior.

The Divergent Cardiovascular Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Blockers in Adult Patients With Type 2 Diabetes Mellitus.

PubMed

Strauss, Martin H; Hall, Alistair S

2018-04-01

The renin angiotensin aldosterone system (RAAS) plays a central role in the pathophysiology of hypertension and vascular disease. Angiotensin-converting enzyme inhibitors (ACEi's) suppress angiotensin II (ANG II) concentrations, whereas angiotensin II type 1 (AT 1 ) receptor blockers (ARBs) block the binding of ANG II to AT 1 receptors. ACEi's and ARBs are both effective antihypertensive agents and produce similar risk reductions for stroke, a blood pressure-dependent phenomenon. ACEi's also reduce the risk for myocardial infarction (MI) and all-cause mortality in high-risk hypertensive patients as well as in people with diabetes, vascular disease and congestive heart failure. ARBs, in contrast, do not reduce the risk for MI or death in randomized clinical trials when assessed vs. placebo. Systematic reviews of ARBs that include meta-analyses or metaregression analyses confirm that ARBs lack the cardiovascular-protective effects of ACEi's. Practice guidelines, especially those for high-risk patients, such as those with diabetes mellitus, should reflect the evidence that ACEi's and ARBs have divergent cardiovascular effects: ACEi's reduce mortality, whereas ARBs do not. ACEi's should remain the preferred RAAS inhibitor for patients at high risk. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II.

PubMed

Versyck, Barbara; van Geffen, Geert-Jan; Van Houwe, Patrick

2017-08-01

The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. A prospective randomized double blind placebo-controlled study. A secondary hospital. 140 breast cancer stage 1-3 patients undergoing mastectomy or tumorectomy with sentinel node or axillary node dissection. Patients were randomized to receive either a Pecs block with levobupivacaine 0.25% (n=70) or placebo block with saline (n=70). The pain levels were evaluated by Numeric Rating Scale (NRS) pain scores at 15-minute intervals during the post anesthesia care unit stay time (PACU), at 2-hour intervals for the first 24h on the ward and at 4-hour intervals for the next 24h. Intraoperative and postoperative opioid consumption were recorded during the full stay. Patient satisfaction was evaluated upon discharge using a 10-point scale. Intraoperative sufentanil requirements were comparable for the Pecs and placebo group (8.0±3.5μg and 7.8±3.0μg, P=0.730). Patients in the Pecs group experienced significantly less pain than patients in the control group (P=0.048) during their PACU stay. Furthermore, patients in the Pecs group required significant less postoperative opioids (9.16±10.15mg and 14.97±14.38mg morphine equivalent, P=0.037) and required significant fewer postsurgical opioid administration interventions than patients in the control group (P=0.045). Both patient-groups were very satisfied about their management (9.6±0.6 and 9.1±1.8 on a 10-point scale, P=0.211). The Pecs block reduces postsurgical opioid consumption during the PACU stay time for patients undergoing breast surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

17 CFR 43.6 - Block trades and large notional off-facility swaps.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., Poland, Russia, and Turkey; or (ii) By unique currency combinations not included in paragraph (b)(4)(i... the date of publication. (g) Required notification. (1) Block trade election. (i) The parties to a... election to have the publicly reportable swap transaction treated as a block trade. (ii) The registered...

Tachykinins Stimulate a Subset of Mouse Taste Cells

PubMed Central

Grant, Jeff

2012-01-01

The tachykinins substance P (SP) and neurokinin A (NKA) are present in nociceptive sensory fibers expressing transient receptor potential cation channel, subfamily V, member 1 (TRPV1). These fibers are found extensively in and around the taste buds of several species. Tachykinins are released from nociceptive fibers by irritants such as capsaicin, the active compound found in chili peppers commonly associated with the sensation of spiciness. Using real-time Ca2+-imaging on isolated taste cells, it was observed that SP induces Ca2+ -responses in a subset of taste cells at concentrations in the low nanomolar range. These responses were reversibly inhibited by blocking the SP receptor NK-1R. NKA also induced Ca2+-responses in a subset of taste cells, but only at concentrations in the high nanomolar range. These responses were only partially inhibited by blocking the NKA receptor NK-2R, and were also inhibited by blocking NK-1R indicating that NKA is only active in taste cells at concentrations that activate both receptors. In addition, it was determined that tachykinin signaling in taste cells requires Ca2+-release from endoplasmic reticulum stores. RT-PCR analysis further confirmed that mouse taste buds express NK-1R and NK-2R. Using Ca2+-imaging and single cell RT-PCR, it was determined that the majority of tachykinin-responsive taste cells were Type I (Glial-like) and umami-responsive Type II (Receptor) cells. Importantly, stimulating NK-1R had an additive effect on Ca2+ responses evoked by umami stimuli in Type II (Receptor) cells. This data indicates that tachykinin release from nociceptive sensory fibers in and around taste buds may enhance umami and other taste modalities, providing a possible mechanism for the increased palatability of spicy foods. PMID:22363709

Incorporating engine health monitoring capability into the SSME Block II controller

NASA Astrophysics Data System (ADS)

Clarke, James W.; Copa, Roderick J.

An account is given of the architecture of the SSME's Block II controller's architecture, its incorporation of smart input electronics (SIE), and the potential benefits of this technology in SSME health-monitoring capabilities. SIE allows the Block II controller to conduct its control functions while simultaneously furnishing the computational capabilities and sensor input interface for any newly defined health-monitoring functions. It is expected that the SIE technology may be directly transferred to any follow-on engine design.

Troglitazone stimulates {beta}-arrestin-dependent cardiomyocyte contractility via the angiotensin II type 1{sub A} receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilley, Douglas G., E-mail: douglas.tilley@jefferson.edu; Center for Translational Medicine, Thomas Jefferson University; Nguyen, Anny D.

2010-06-11

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPAR{gamma}-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPAR{gamma} activity, thus we hypothesized that a PPAR{gamma} agonist may exert physiologic effects via the angiotensin II type 1{sub A} receptor (AT1{sub A}R). In AT1{sub A}R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPAR{gamma} agonist troglitazone (Trog) enhanced AT1{sub A}R internalization and recruitment of endogenous {beta}-arrestin1/2 ({beta}arr1/2) to the AT1{sub A}R. A fluorescence assay to measure diacylglycerolmore » (DAG) accumulation showed that although Ang II induced AT1{sub A}R-G{sub q} protein-mediated DAG accumulation, Trog had no impact on DAG generation. Trog-mediated recruitment of {beta}arr1/2 was selective to AT1{sub A}R as the response was prevented by an ARB- and Trog-mediated {beta}arr1/2 recruitment to {beta}1-adrenergic receptor ({beta}1AR) was not observed. In isolated mouse cardiomyocytes, Trog increased both % and rate of cell shortening to a similar extent as Ang II, effects which were blocked with an ARB. Additionally, these effects were found to be {beta}arr2-dependent, as cardiomyocytes isolated from {beta}arr2-KO mice showed blunted contractile responses to Trog. These findings show for the first time that the PPAR{gamma} agonist Trog acts at the AT1{sub A}R to simultaneously block G{sub q} protein activation and induce the recruitment of {beta}arr1/2, which leads to an increase in cardiomyocyte contractility.« less

Programmable RNA Cleavage and Recognition by a Natural CRISPR-Cas9 System from Neisseria meningitidis.

PubMed

Rousseau, Beth A; Hou, Zhonggang; Gramelspacher, Max J; Zhang, Yan

2018-03-01

The microbial CRISPR systems enable adaptive defense against mobile elements and also provide formidable tools for genome engineering. The Cas9 proteins are type II CRISPR-associated, RNA-guided DNA endonucleases that identify double-stranded DNA targets by sequence complementarity and protospacer adjacent motif (PAM) recognition. Here we report that the type II-C CRISPR-Cas9 from Neisseria meningitidis (Nme) is capable of programmable, RNA-guided, site-specific cleavage and recognition of single-stranded RNA targets and that this ribonuclease activity is independent of the PAM sequence. We define the mechanistic feature and specificity constraint for RNA cleavage by NmeCas9 and also show that nuclease null dNmeCas9 binds to RNA target complementary to CRISPR RNA. Finally, we demonstrate that NmeCas9-catalyzed RNA cleavage can be blocked by three families of type II-C anti-CRISPR proteins. These results fundamentally expand the targeting capacities of CRISPR-Cas9 and highlight the potential utility of NmeCas9 as a single platform to target both RNA and DNA. Copyright © 2018 Elsevier Inc. All rights reserved.

[Sudden cardiac death due to sarcoidosis. Case report].

PubMed

Sejben, István; Som, Zoltán; Cserni, Gábor

2017-07-01

Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067-1070.

Cholesterol and related sterols autoxidation.

PubMed

Zerbinati, Chiara; Iuliano, Luigi

2017-10-01

Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

Dopamine Neurons Change the Type of Excitability in Response to Stimuli

PubMed Central

Gutkin, Boris S.; Lapish, Christopher C.; Kuznetsov, Alexey

2016-01-01

The dynamics of neuronal excitability determine the neuron’s response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency “balanced” state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or co-activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I excitability in dopamine neurons might be important for low firing rates and fine-tuning basal dopamine levels, while switching excitability to type II during NMDAR and AMPAR activation may facilitate a transient increase in dopamine concentration, as type II neurons are more amenable to synchronization by mutual excitation. PMID:27930673

The seed dormancy defect of Arabidopsis mutants lacking the transcript elongation factor TFIIS is caused by reduced expression of the DOG1 gene.

PubMed

Mortensen, Simon A; Grasser, Klaus D

2014-01-03

TFIIS is a transcript elongation factor that facilitates transcription by RNA polymerase II, as it assists the enzyme to bypass blocks to mRNA synthesis. Previously, we have reported that Arabidopsis plants lacking TFIIS exhibit reduced seed dormancy. Among the genes differentially expressed in tfIIs seeds, the DOG1 gene was identified that is a known QTL for seed dormancy. Here we have analysed plants that overexpress TFIIS in wild type background, or that harbour an additional copy of DOG1 in tfIIs mutant background. These experiments demonstrate that the down-regulation of DOG1 expression causes the seed dormancy phenotype of tfIIs mutants. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Plumbing Specialist II & III, 3-22. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

These military-developed curriculum materials consist of a course description, course chart, plan of instruction, lesson plans, study guides, and workbooks for use in training plumbing specialists II and III. Covered in the course blocks are building waste systems and exterior and interior supply systems. Course block II, on building waste…

The impact of nanocontact on nanowire based nanoelectronics.

PubMed

Lin, Yen-Fu; Jian, Wen-Bin

2008-10-01

Nanowire-based nanoelectronic devices will be innovative electronic building blocks from bottom up. The reduced nanocontact area of nanowire devices magnifies the contribution of contact electrical properties. Although a lot of two-contact-based ZnO nanoelectronics have been demonstrated, the electrical properties bringing either from the nanocontacts or from the nanowires have not been considered yet. High quality ZnO nanowires with a small deviation and an average diameter of 38 nm were synthesized to fabricate more than thirty nanowire devices. According to temperature behaviors of current-voltage curves and resistances, the devices could be grouped into three types. Type I devices expose thermally activated transport in ZnO nanowires and they could be considered as two Ohmic nanocontacts of the Ti electrode contacting directly on the nanowire. For those nanowire devices having a high resistance at room temperatures, they can be fitted accurately with the thermionic-emission theory and classified into type II and III devices according to their rectifying and symmetrical current-voltage behaviors. The type II device has only one deteriorated nanocontact and the other one Ohmic contact on single ZnO nanowire. An insulating oxide layer with thickness less than 20 nm should be introduced to describe electron hopping in the nanocontacts, so as to signalize one- and high-dimensional hopping conduction in type II and III devices.

alpha-Putrescinylthymine and the sensitivity of bacteriophage phi W-14 DNA to restriction endonucleases.

PubMed Central

Miller, P B; Wakarchuk, W W; Warren, R A

1985-01-01

The modified base alpha-putrescinylthymine (putT) in phi W-14 DNA blocks cleavage of the DNA by 17 of 32 Type II restriction endonucleases. The enzymes cleaving the DNA do so to widely varying extents. The frequencies of cleavage of three altered forms of the DNA show that putT blocks recognition sites either when it occurs within the site or when it is in a sequence flanking the site. The blocking is dependent on both charge and steric factors. The charge effects can be greater than the steric effects for some of the enzymes tested. All the enzymes cleaving phi W-14 DNA release discrete fragments, showing that the distribution of putT is ordered. The cleavage frequencies for different enzymes suggest that the sequence CAputTG occurs frequently in the DNA. Only TaqI of the enzymes tested appeared not to be blocked by putT, but it was slowed down. TaqI generated fragments are joinable by T4 DNA ligase. PMID:2987859

C-terminal sequence of amyloid-resistant type F apolipoprotein A-II inhibits amyloid fibril formation of apolipoprotein A-II in mice

PubMed Central

Sawashita, Jinko; Zhang, Beiru; Hasegawa, Kazuhiro; Mori, Masayuki; Naiki, Hironobu; Kametani, Fuyuki; Higuchi, Keiichi

2015-01-01

In murine senile amyloidosis, misfolded serum apolipoprotein (apo) A-II deposits as amyloid fibrils (AApoAII) in a process associated with aging. Mouse strains carrying type C apoA-II (APOA2C) protein exhibit a high incidence of severe systemic amyloidosis. Previously, we showed that N- and C-terminal sequences of apoA-II protein are critical for polymerization into amyloid fibrils in vitro. Here, we demonstrate that congenic mouse strains carrying type F apoA-II (APOA2F) protein, which contains four amino acid substitutions in the amyloidogenic regions of APOA2C, were absolutely resistant to amyloidosis, even after induction of amyloidosis by injection of AApoAII. In vitro fibril formation tests showed that N- and C-terminal APOA2F peptides did not polymerize into amyloid fibrils. Moreover, a C-terminal APOA2F peptide was a strong inhibitor of nucleation and extension of amyloid fibrils during polymerization. Importantly, after the induction of amyloidosis, we succeeded in suppressing amyloid deposition in senile amyloidosis-susceptible mice by treatment with the C-terminal APOA2F peptide. We suggest that the C-terminal APOA2F peptide might inhibit further extension of amyloid fibrils by blocking the active ends of nuclei (seeds). We present a previously unidentified model system for investigating inhibitory mechanisms against amyloidosis in vivo and in vitro and believe that this system will be useful for the development of novel therapies. PMID:25675489

[Treatment effects of magnetic Twin-block appliance for class II cases].

PubMed

Wu, Jian-Yong; Liu, Jian; Li, Qi-Shun; Xu, Tian-Min; Lin, Jiu-Xiang

2007-09-01

To evaluate the effects of magnetic Twin-block appliance in the treatment of skeletal class II cases. The magnetic Twin-block appliance was embedded with two pairs of neodymium-iron-boron (Nd(2)Fe(14)B) rare earth permanent magnets in the upper and lower inclined planes of Twin-block appliance. The sample comprised of 13 skeletal class II patients in the late mixed or early permanent dentition treated by magnetic Twin-block appliance. Cephalometric films were taken before and after treatment. Helix CT images of the temporomandibular joint (TMJ) in all patients were examined before treatment (T1), during treatment (4 months after appliance placement, T2), after treatment (T3) and one year after treatment (T4). A double contour image was detected in the superior posterior part of the condylar head on the pseudo-sagittal reconstruction plane pictures of T2 in 11 patients. The double contour image could be observed in most patients as well. This image also exhibited on the pictures of T3 in several patients. On the pictures of T2 and T3 in some patients, interruption of cortical bone and "bifurcation phenomenon" of condyles were shown. Pictures of T1 and T4 were similar and no signs of remodeling of TMJ were observed. Cephalometric analysis revealed significant changes in the maxillofacial structure after treatment. The profile of patients improved. Bone remodeling of condyle occurred during the magnetic Twin-block treatment in class II patients. Magnetic Twin-block appliance was effective in the treatment of the growing skeletal class II patients.

Transthoracic Arteriovenous Graft Repair With the Pectoralis (PECS) II Nerve Block for Primary Intraoperative Anesthesia and Postoperative Analgesia: A Case Report.

PubMed

Farkas, Gabriel; Weber, Garret; Miller, Jonathon; Xu, Jeff

2018-05-07

The PECS II nerve block is a relatively new regional anesthetic technique that targets the medial and lateral pectoral nerves, as well as the lateral cutaneous branches of the intercostal nerves. It has been described for surgical cases involving the breast, as an adjunct or alternative to neuraxial or paravertebral techniques. This case report describes the first successful use of the PECS II nerve block placed using ultrasound guidance as the primary anesthetic and postoperative analgesic in a non-breast-related chest wall surgery.

BlockLogo: visualization of peptide and sequence motif conservation

PubMed Central

Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian; Sun, Jing; Schönbach, Christian; Reinherz, Ellis L.; Zhang, Guang Lan; Brusic, Vladimir

2013-01-01

BlockLogo is a web-server application for visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class I and class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://methilab.bu.edu/blocklogo/ PMID:24001880

Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery.

PubMed

Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

2015-01-01

the aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. in this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5 μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25 μg fentanyl. All the patients remained in the seated position for 5 min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. spinal saddle block using hyperbaric levobupivacaine with both 12.5 μg and 25 μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery].

PubMed

Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

2015-01-01

The aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. In this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25μg fentanyl. All the patients remained in the seated position for 5min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. Motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. Spinal saddle block using hyperbaric levobupivacaine with both 12.5μg and 25μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Cattaraugus Creek Harbor, New York General Design Memorandum. Phase II (Detailed Design). Volume I. Main Report-GDM II.

DTIC Science & Technology

1976-03-01

of the abetract entered In Block 20, If different from Report) I$. SUPPLEMENTARY NOTES .4 19. KEY WORDS (Continue on reverse aide If neceesary and...Identify by block number) Harbors Cattaraugus Creek Flood Control 20O T’rlq 4CT Caiweut -t reverse se 0 neceeeely mid Identify by block number) The... blocked by the sand bar and lake ice at the creek mouth. During discharges developed by the com- bination of rainfall and snow melt, ice jams raise the

Cold bupivacaine versus magnesium sulfate added to room temperature bupivacaine in sonar-guided femoral and sciatic nerve block in arthroscopic anterior cruciate ligament reconstruction surgery.

PubMed

Alzeftawy, Ashraf Elsayed; El-Daba, Ahmad Ali

2016-01-01

Cooling of local anesthetic potentiates its action and increases its duration. Magnesium sulfate (MgSo 4 ) added to local anesthetic prolongs the duration of anesthesia and postoperative analgesia with minimal side effects. The aim of this prospective, randomized, double-blind study was to compare the effect of cold to 4°C bupivacaine 0.5% and Mg added to normal temperature (20-25°C) bupivacaine 0.5% during sonar-guided combined femoral and sciatic nerve blocks on the onset of sensory and motor block, intraoperative anesthesia, duration of sensory and motor block, and postoperative analgesia in arthroscopic anterior cruciate ligament (ACL) reconstruction surgery. A total of 90 American Society of Anesthesiologists classes I and II patients who were scheduled to undergo elective ACL reconstruction were enrolled in the study. The patients were randomly allocated to 3 equal groups to receive sonar-guided femoral and sciatic nerve blocks. In Group I, 17 ml of room temperature (20-25°C) 0.5% bupivacaine and 3 ml of room temperature saline were injected for each nerve block whereas in Group II, 17 ml of cold (4°C) 0.5% bupivacaine and 3 ml of cold saline were injected for each nerve block. In Group III, 17 ml of room temperature 0.5% bupivacaine and 3 ml of MgSo 4 5% were injected for each nerve block. The onset of sensory and motor block was evaluated every 3 min for 30 min. Surgery was started after complete sensory and motor block were achieved. Intraoperatively, the patients were evaluated for heart rate and mean arterial pressure, rescue analgesic and sedative requirements plus patient and surgeon satisfaction. Postoperatively, hemodynamics, duration of analgesia, resolution of motor block, time to first analgesic, total analgesic consumption, and the incidence of side effects were recorded. There was no statistically significant difference in demographic data, mean arterial pressure, heart rate, and duration of surgery. Onset of both sensory and motor block was significantly shorter in both Groups II and III compared to Group I. Intraoperative anesthetic quality was comparable between groups with good patient and surgeon satisfaction. The time to first analgesia was significantly longer in Groups II and III compared to Group I with nonsignificant difference between each other. Moreover, the total opioid consumption was significantly lower in Groups II and III and duration of analgesia and motor block were significantly longer in Groups II and III compared to Group I. There was no difference in the incidence of side effects. The use of cold 0.5% bupivacaine or the addition of Mg to normal temperature 0.5% bupivacaine prolongs the sensory and motor block duration without increasing side effects and enhances the quality of intra- and post-operative analgesia with better patient satisfaction in sonar-guided femoral and sciatic nerve block for arthroscopic ACL reconstruction surgery.

Mdt1 Facilitates Efficient Repair of Blocked DNA Double-Strand Breaks and Recombinational Maintenance of Telomeres▿

PubMed Central

Pike, Brietta L.; Heierhorst, Jörg

2007-01-01

DNA recombination plays critical roles in DNA repair and alternative telomere maintenance. Here we show that absence of the SQ/TQ cluster domain-containing protein Mdt1 (Ybl051c) renders Saccharomyces cerevisiae particularly hypersensitive to bleomycin, a drug that causes 3′-phospho-glycolate-blocked DNA double-strand breaks (DSBs). mdt1Δ also hypersensitizes partially recombination-defective cells to camptothecin-induced 3′-phospho-tyrosyl protein-blocked DSBs. Remarkably, whereas mdt1Δ cells are unable to restore broken chromosomes after bleomycin treatment, they efficiently repair “clean” endonuclease-generated DSBs. Epistasis analyses indicate that MDT1 acts in the repair of bleomycin-induced DSBs by regulating the efficiency of the homologous recombination pathway as well as telomere-related functions of the KU complex. Moreover, mdt1Δ leads to severe synthetic growth defects with a deletion of the recombination facilitator and telomere-positioning factor gene CTF18 already in the absence of exogenous DNA damage. Importantly, mdt1Δ causes a dramatic shift from the usually prevalent type II to the less-efficient type I pathway of recombinational telomere maintenance in the absence of telomerase in liquid senescence assays. As telomeres resemble protein-blocked DSBs, the results indicate that Mdt1 acts in a novel blocked-end-specific recombination pathway that is required for the efficiency of both drug-induced DSB repair and telomerase-independent telomere maintenance. PMID:17636027

Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases

PubMed Central

Schwartz, Daniella M.; Bonelli, Michael; Gadina, Massimo; O’Shea, John J.

2015-01-01

Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies—including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs block the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease. PMID:26633291

Comprehensive review of neurophysiologic basis and diagnostic interventions in managing chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Singh, Vijay; Derby, Richard; Fellows, Bert; Falco, Frank J E; Datta, Sukdeb; Smith, Howard S; Hirsch, Joshua A

2009-01-01

Understanding the neurophysiological basis of chronic spinal pain and diagnostic interventional techniques is crucial in the proper diagnosis and management of chronic spinal pain. Central to the understanding of the structural basis of chronic spinal pain is the provision of physical diagnosis and validation of patient symptomatology. It has been shown that history, physical examination, imaging, and nerve conduction studies in non-radicular or discogenic pain are unable to diagnose the precise cause in 85% of the patients. In contrast, controlled diagnostic blocks have been shown to determine the cause of pain in as many as 85% of the patients. To provide evidence-based clinical practice guidelines for diagnostic interventional techniques. Best evidence synthesis. Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II. Diagnostic criteria established by systematic reviews were utilized with controlled diagnostic blocks. Diagnostic criteria included at least 80% pain relief with controlled local anesthetic blocks with the ability to perform multiple maneuvers which were painful prior to the diagnostic blocks for facet joint and sacroiliac joint blocks, whereas for provocation discography, the criteria included concordant pain upon stimulation of the target disc with 2 adjacent discs producing no pain at all. The indicated level of evidence for diagnostic lumbar, cervical, and thoracic facet joint nerve blocks is Level I or II-1. The indicated evidence is Level II-2 for lumbar and cervical discography, whereas it is Level II-3 for thoracic provocation discography. The evidence for diagnostic sacroiliac joint nerve blocks is Level II-2. Level of evidence for selective nerve root blocks for diagnostic purposes is Level II-3. Limitations of this guideline preparation include a continued paucity of literature and conflicts in preparation of systematic reviews and guidelines. These guidelines include the evaluation of evidence for diagnostic interventional procedures in managing chronic spinal pain and recommendations. However, these guidelines do not constitute inflexible treatment recommendations. These guidelines also do not represent a "standard of care."

Digital classification of Landsat data for vegetation and land-cover mapping in the Blackfoot River watershed, southeastern Idaho

USGS Publications Warehouse

Pettinger, L.R.

1982-01-01

This paper documents the procedures, results, and final products of a digital analysis of Landsat data used to produce a vegetation and landcover map of the Blackfoot River watershed in southeastern Idaho. Resource classes were identified at two levels of detail: generalized Level I classes (for example, forest land and wetland) and detailed Levels II and III classes (for example, conifer forest, aspen, wet meadow, and riparian hardwoods). Training set statistics were derived using a modified clustering approach. Environmental stratification that separated uplands from lowlands improved discrimination between resource classes having similar spectral signatures. Digital classification was performed using a maximum likelihood algorithm. Classification accuracy was determined on a single-pixel basis from a random sample of 25-pixel blocks. These blocks were transferred to small-scale color-infrared aerial photographs, and the image area corresponding to each pixel was interpreted. Classification accuracy, expressed as percent agreement of digital classification and photo-interpretation results, was 83.0:t 2.1 percent (0.95 probability level) for generalized (Level I) classes and 52.2:t 2.8 percent (0.95 probability level) for detailed (Levels II and III) classes. After the classified images were geometrically corrected, two types of maps were produced of Level I and Levels II and III resource classes: color-coded maps at a 1:250,000 scale, and flatbed-plotter overlays at a 1:24,000 scale. The overlays are more useful because of their larger scale, familiar format to users, and compatibility with other types of topographic and thematic maps of the same scale.

Mechanism of RNA polymerase II bypass of oxidative cyclopurine DNA lesions

DOE PAGES

Walmacq, Celine; Wang, Lanfeng; Chong, Jenny; ...

2015-01-20

In human cells, the oxidative DNA lesion 8,5'-cyclo-2'-deoxyadenosine (CydA) induces prolonged stalling of RNA polymerase II (Pol II) followed by transcriptional bypass, generating both error-free and mutant transcripts with AMP misincorporated immediately downstream from the lesion. Here, we present biochemical and crystallographic evidence for the mechanism of CydA recognition. Pol II stalling results from impaired loading of the template base (5') next to CydA into the active site, leading to preferential AMP misincorporation. Such predominant AMP insertion, which also occurs at an abasic site, is unaffected by the identity of the 5´-templating base, indicating that it derives from nontemplated synthesismore » according to an A rule known for DNA polymerases and recently identified for Pol II bypass of pyrimidine dimers. Subsequent to AMP misincorporation, Pol II encounters a major translocation block that is slowly overcome. The translocation block combined with the poor extension of the dA.rA mispair reduce transcriptional mutagenesis. Moreover, increasing the active-site flexibility by mutation in the trigger loop, which increases the ability of Pol II to accommodate the bulky lesion, and addition of transacting factor TFIIF facilitate CydA bypass. Thus, blocking lesion entry to the active site, trans-lesion A rule synthesis, and translocation block are common features of transcription across different bulky DNA lesions.« less

Laser Generated Magnetic Fields

DTIC Science & Technology

1976-06-01

30, II dttlormnt from Rmpori) IS. SUPPLEMENTARY NOTES 19. KEY WORDS (Continue on tororoo aldo II nocoommry and Idontlty by block nuaibar) Crater...dependence of laser generated magnetic fields Laser crater cross-sections X-ray detection from laser plasma 20. ABSTRACT (Contlmio on tovormo aid* II...nacaaaary and Idontlty ay block mmtbor) A sequence of laser pulses focussed onto the same spot on a target produces evaporation of target material and the

Mononuclear, trinuclear, and hetero-trinuclear supramolecular complexes containing a new tri-sulfonate ligand and cobalt(II)/copper(II)-(1,10-phenanthroline) 2 building blocks

NASA Astrophysics Data System (ADS)

Yu, Yunfang; Wei, Yongqin; Broer, Ria; Sa, Rongjian; Wu, Kechen

2008-03-01

Novel mononuclear, trinuclear, and hetero-trinuclear supermolecular complexes, [Co(phen) 2(H 2O)(HTST)]·2H 2O ( 1), [Co 3(phen) 6(H 2O) 2(TST) 2]·7H 2O ( 2), and [Co 2Cu(phen) 6(H 2O) 2(TST) 2]·10H 2O ( 3), have been synthesized by the reactions of a new tri-sulfonate ligand (2,4,6-tris(4-sulfophenylamino)-1,3,5-triazine, H 3TST) with the M2+ ( M=Co, Cu) and the second ligand 1,10-phenanthroline (phen). Complex 1 contains a cis-Co(II)(phen) 2 building block and an HTST as monodentate ligand; complex 2 consists of two TST as bidentate ligands connecting one trans- and two cis-Co(II)(phen) 2 building blocks; complex 3 is formed by replacing the trans-Co(II)(phen) 2 in 2 with a trans-Cu(II)(phen) 2, which is the first reported hetero-trinuclear supramolecular complex containing both the Co(II)(phen) 2 and Cu(II)(phen) 2 as building blocks. The study shows the flexible multifunctional self-assembly capability of the H 3TST ligands presenting in these supramolecular complexes through coordinative, H-bonding and even π- π stacking interactions. The photoluminescent optical properties of these complexes are also investigated and discussed as well as the second-order nonlinear optical properties of 1.

HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4+ T Cell Responses

PubMed Central

Wang, Mingjun; Larsen, Mette V.; Nielsen, Morten; Harndahl, Mikkel; Justesen, Sune; Dziegiel, Morten H.; Buus, Søren; Tang, Sheila T.; Lund, Ole; Claesson, Mogens H.

2010-01-01

Background Identification of human leukocyte antigen class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the development of new effective peptide-based vaccines. Methodology/Principal Findings In the present work, bioinformatics was used to predict 9mer peptides derived from available influenza A viral proteins with binding affinity for at least one of the 12 HLA-I supertypes. The predicted peptides were then selected in a way that ensured maximal coverage of the available influenza A strains. One hundred and thirty one peptides were synthesized and their binding affinities for the HLA-I supertypes were measured in a biochemical assay. Influenza-specific T cell responses towards the peptides were quantified using IFNγ ELISPOT assays with peripheral blood mononuclear cells (PBMC) from adult healthy HLA-I typed donors as responder cells. Of the 131 peptides, 21 were found to induce T cell responses in 19 donors. In the ELISPOT assay, five peptides induced responses that could be totally blocked by the pan-specific anti-HLA-I antibody W6/32, whereas 15 peptides induced responses that could be completely blocked in the presence of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC depleted of CD4+ or CD8+ T cells prior to the ELISPOT culture revealed that effectors are either CD4+ (the majority of reactivities) or CD8+ T cells, never a mixture of these subsets. Three of the peptides, recognized by CD4+ T cells showed binding to recombinant DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 molecules in a recently developed biochemical assay. Conclusions/Significance HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4+ T cell responses restricted by HLA-II molecules. PMID:20479886

MAP kinase-independent signaling in angiotensin II regulation of neuromodulation in SHR neurons.

PubMed

Yang, H; Raizada, M K

1998-09-01

Angiotensin II (Ang II), via its interaction with the angiotensin type 1 (AT1) receptor subtype, causes enhanced stimulation of norepinephrine (NE) neuromodulation. This involves increased transcription of NE transporter, tyrosine hydroxylase, and dopamine ss-hydroxylase genes in Wistar-Kyoto rat (WKY) brain neurons. AT1 receptor-mediated regulation of certain signaling events (such as activation of the Ras-Raf-1-mitogen activated protein (MAP) kinase signaling pathway, nuclear translocation of transcription factors such as Fos and Jun, and the interactions of these factors with AP-1 binding sites) is involved in this NE neuromodulation (Lu et al. J Cell Biol. 1996;135:1609-1617). The aim of this study was to compare the signal transduction mechanism of Ang II regulation of NE neuromodulation in WKY and spontaneously hypertensive rat (SHR) brain neurons, in view of the fact that AT1 receptor expression and Ang II stimulation of NE neuromodulation are higher in SHR neurons compared with WKY neurons. Despite this hyperactivity, Ang II stimulation of Ras, Raf-1, and MAP kinase activities was comparable between the neurons from WKY and SHR. Similarly, central injections of Ang II caused a comparable stimulation of MAP kinase in the hypothalamic and brain stem areas of adult WKY and SHR. Inhibition of MAP kinase by either an MAP kinase kinase inhibitor (PD98059) or an MAP kinase antisense oligonucleotide completely attenuated the stimulatory effects of Ang II on [3H]-NE uptake, NE transporter mRNA, and tyrosine hydroxylase mRNA levels in WKY neurons. These treatments resulted in only 43% to 50% inhibition of [3H]-NE uptake and NE transporter and tyrosine hydroxylase mRNAs in SHR neurons. Thus, Ang II stimulation of NE neuromodulation was completely blocked by MAP kinase inhibition in WKY neurons and only partially blocked in the SHR neurons. These observations suggest the presence of an additional signal transduction pathway involved in NE neuromodulation in SHR neurons that is independent of the MAP kinase pathway.

Comparison of Maternal and Neonatal Effects of Combined Spinal Epidural Anaesthesia in Either the Sitting or Lateral Position During Elective Cesarean Section

PubMed Central

Tan, Ece Dumanlar; Günaydın, Berrin

2014-01-01

Objective Our goal was to demonstrate which position would be hemodynamically and technically better by comparing the effects of combined spinal epidural (CSE) in the sitting or lateral decubitus position for elective cesarean deliveries on maternal and neonatal parameters and ephedrine requirement. Methods Sixty parturients were randomly assigned into two groups to perform CSE in the sitting (Group I, n=30) or right lateral decubitus position (Group II, n=30) using hyperbaric 10 mg bupivacaine and 20 μg fentanyl. Mean arterial pressure (MAP), heart rate (HR), and characteristics of sensory and motor block were recorded from intrathecal drug administration until the end of surgery. Ephedrine and 1st analgesic requirement, number of attempts to perform CSE, incidence of paresthesia during spinal needle insertion, and Apgar scores were recorded. Results Ephedrine requirements and HR changes were similar in both groups. However, MAP values at 45 min in Group II were significantly less than in Group I. Maximum sensory block levels in Group II were significantly higher than in Group I. Despite similar motor block recovery times in both groups, regression times of sensory block and 1st analgesic requirement in Group II were significantly longer than in Group I. Incidence of paresthesia due to spinal needle (3.3% versus 20% in Groups I and II, respectively) and number of attempts to perform CSE (26.7% versus 60% in Groups I and II, respectively) were significantly higher in Group II. Apgar scores were similar in both groups. Conclusion Performing CSE in the sitting position would be safer and easier because higher and earlier onset of sensory block, and a greater number attempts at epidural insertion and paresthesia develop to spinal needle insertion in the right lateral position. PMID:27366384

Gallium nitrate ameliorates type II collagen-induced arthritis in mice.

PubMed

Choi, Jae-Hyeog; Lee, Jong-Hwan; Roh, Kug-Hwan; Seo, Su-Kil; Choi, Il-Whan; Park, Sae-Gwang; Lim, Jun-Goo; Lee, Won-Jin; Kim, Myoung-Hun; Cho, Kwang-rae; Kim, Young-Jae

2014-05-01

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA. Copyright © 2014 Elsevier B.V. All rights reserved.

Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus.

PubMed

Ogiwara, Haru; Yasui, Fumihiko; Munekata, Keisuke; Takagi-Kamiya, Asako; Munakata, Tsubasa; Nomura, Namiko; Shibasaki, Futoshi; Kuwahara, Kazuhiko; Sakaguchi, Nobuo; Sakoda, Yoshihiro; Kida, Hiroshi; Kohara, Michinori

2014-01-01

Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus

PubMed Central

Ogiwara, Haru; Yasui, Fumihiko; Munekata, Keisuke; Takagi-Kamiya, Asako; Munakata, Tsubasa; Nomura, Namiko; Shibasaki, Futoshi; Kuwahara, Kazuhiko; Sakaguchi, Nobuo; Sakoda, Yoshihiro; Kida, Hiroshi; Kohara, Michinori

2015-01-01

Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage. PMID:24200852

Reversible second degree atrioventricular block after a severe sickle cell crisis.

PubMed

Jaeggi, E; Bolens, M; Friedli, B

1998-01-01

Despite the high prevalence of sickle cell disease and trait in the black population and its serious potential for microinfarction, there are only a few reports on acute myocardial damage during vasoocclusive crisis. We report a unique case of transient second degree atrioventricular (A-V) block of Mobitz I and II type during a severe sickle cell crisis. Localized high ventricular septum hypoperfusion demonstrated by a 99mTc-MIBI radionuclide study and reversible echocardiographic wall motion abnormalities in the same area were strong indicators for a local ischemic event in the A-V node and His bundle area, explaining the observed transient conduction abnormalities. The present report draws attention to a potentially lethal complication of sickle cell crisis.

Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

PubMed

Lai, Zengzu; Schreiber, John R

2009-05-21

Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

Dopamine modulation of transient receptor potential vanilloid type 1 (TRPV1) receptor in dorsal root ganglia neurons.

PubMed

Chakraborty, Saikat; Rebecchi, Mario; Kaczocha, Martin; Puopolo, Michelino

2016-03-15

The transient receptor potential vanilloid type 1 (TRPV1) receptor plays a key role in the modulation of nociceptor excitability. To address whether dopamine can modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamine receptor agonists were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons. Dopamine or SKF 81297 (an agonist at D1/D5 receptors), caused inhibition of both inward and outward currents by ∼60% and ∼48%, respectively. The effect of SKF 81297 was reversed by SCH 23390 (an antagonist at D1/D5 receptors), confirming that it was mediated by activation of D1/D5 dopamine receptors. In contrast, quinpirole (an agonist at D2 receptors) had no significant effect on the capsaicin-activated current. Inhibition of the capsaicin-activated current by SKF 81297 was mediated by G protein coupled receptors (GPCRs), and highly dependent on external calcium. The inhibitory effect of SKF 81297 on the capsaicin-activated current was not affected when the protein kinase A (PKA) activity was blocked with H89, or when the protein kinase C (PKC) activity was blocked with bisindolylmaleimide II (BIM). In contrast, when the calcium-calmodulin-dependent protein kinase II (CaMKII) was blocked with KN-93, the inhibitory effect of SKF 81297 on the capsaicin-activated current was greatly reduced, suggesting that activation of D1/D5 dopamine receptors may be preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to modulate incoming noxious stimuli. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Combined spinal epidural anesthesia during colon surgery in a high-risk patient: case report.

PubMed

Imbelloni, Luiz Eduardo; Fornasari, Marcos; Fialho, José Carlos

2009-01-01

Combined spinal epidural anesthesia (CSEA) has advantages over single injection epidural or subarachnoid blockades. The objective of this report was to present a case in which segmental subarachnoid block can be an effective technique for gastrointestinal surgery with spontaneous respiration. Patient with physical status ASA III, with diabetes mellitus type II, hypertension, and chronic obstructive pulmonary disease was scheduled for resection of a right colon tumor. Combined spinal epidural block was performed in the T5-T6 space and 8 mg of 0.5% isobaric bupivacaine with 50 microg of morphine were injected in the subarachnoid space. The epidural catheter (20G) was introduced four centimeters in the cephalad direction. Sedation was achieved with fractionated doses of 1 mg of midazolam (total of 6 mg). A bolus of 25 mg of 0.5% bupivacaine was administered through the catheter two hours after the subarachnoid block. Vasopressors and atropine were not used. This case provides evidence that segmental spinal block can be the anesthetic technique used in gastrointestinal surgeries with spontaneous respiration.

Increased prevalence of third-degree atrioventricular block in patients with type II diabetes mellitus.

PubMed

Movahed, Mohammad-Reza; Hashemzadeh, Mehrtash; Jamal, M Mazen

2005-10-01

Diabetes mellitus (DM) is a major risk for cardiovascular disease and mortality. There is some evidence that third-degree atrioventricular (AV) block occurs more commonly in patients with DM. In this study, we evaluated any possible association between DM and third-degree AV block using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in a very large inpatient database. We used patient treatment files containing discharge diagnoses using ICD-9 codes of inpatient treatment from all Veterans Health Administration hospitals. The cohort was stratified using the ICD-9-CM code for DM (n = 293,124), a control group with hypertension but no DM (n = 552,623), and the ICD-9 code for third-degree AV block (426.0) and smoking (305.1, V15.82). We performed multivariate analysis adjusting for coronary artery disease, congestive heart failure, smoking, and hyperlipidemia. Continuous and binary variables were analyzed using chi2 and Fisher exact tests. Third-degree AV block diagnosis was present in 3,240 of DM patients (1.1%) vs 3,367 patients (0.6%) in the control group. Using multivariate analysis, DM remained strongly associated with third-degree AV block (odds ratio, 3.1; 95% confidential interval, 3.0 to 3.3; p < 0.0001). Third-degree AV block occurs significantly more in patients with DM. This finding may, in part, explain the high cardiovascular mortality in DM patients.

A simple technique to strengthen the initial and mid-term to long-term stability of the cup during total hip arthroplasty in developmental dysplasia of the hip.

PubMed

Guan, Mingqiang; Zhou, Guanming; Li, Xue

2018-04-01

To assess the effects of a technique of cup blocking screws combined with impaction bone grafting during total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH). From August 2011 to July 2015, 53 patients (59 hips) with DDH in our hospital were treated with THA using the technique of cup blocking screws combined with impaction particulate bone grafting. These patients were prospectively followed, and the clinical and imaging results were collected. Harris hip score (HHS) was raised from 41.24 before surgery to 91.49 at the latest follow-up (p less than 0.001). Length discrepancy (LLD) was reduced from 28.97 mm before surgery to 6.08 mm after surgery (p less than 0.001). No loosening of the cup was detected at the last follow-up. The differences were insignificant in cup inclination and rate of cup coverage among the 3 groups of Crowe type II, type III, and type IV DDH (p greater than 0.05). The technique of cup blocking screws combined with impaction particulate bone grafting is simple and reliable, and it not only simplifies the attainment of initial stability, but also strengthens the mid-term to long-term stability during THA in DDH.

Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

PubMed

Ali, Mahmoud Alhaj; Adem, Abdu; Chandranath, Irwin S; Benedict, Sheela; Pathan, Javed Y; Nagelkerke, Nicolas; Nyberg, Fred; Lewis, Lynley K; Yandle, Tim G; Nicholls, Gary M; Frampton, Chris M; Kazzam, Elsadig

2012-01-01

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System

PubMed Central

Ali, Mahmoud Alhaj; Adem, Abdu; Chandranath, Irwin S.; Benedict, Sheela; Pathan, Javed Y.; Nagelkerke, Nicolas; Nyberg, Fred; Lewis, Lynley K.; Yandle, Tim G.; Nicholls, Gary M.; Frampton, Chris M.; Kazzam, Elsadig

2012-01-01

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP. PMID:22624009

Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice.

PubMed

Blakely, Pennelope K; Huber, Amanda K; Irani, David N

2016-08-25

Alphaviruses can cause fatal encephalitis in humans. Natural infections occur via the bite of infected mosquitos, but aerosol transmissibility makes some of these viruses potential bioterrorism agents. Central nervous system (CNS) host responses contribute to alphavirus pathogenesis in experimental models and are logical therapeutic targets. We investigated whether reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity within the CNS contributes to fatal alphavirus encephalitis in mice. Infected animals were treated systemically with the angiotensin receptor-blocking drug, telmisartan, given its ability to cross the blood-brain barrier, selectively block type-1 angiotensin receptors (AT1R), and inhibit Nox-derived ROS production in vascular smooth muscle and other extraneural tissues. Clinical, virological, biochemical, and histopathological outcomes were followed over time. The importance of the angiotensin II (Ang II)/AT1R axis in disease pathogenesis was confirmed by demonstrating increased Ang II levels in the CNS following infection, enhanced disease survival when CNS Ang II production was suppressed, increased AT1R expression on microglia and tissue-infiltrating myeloid cells, and enhanced disease survival in AT1R-deficient mice compared to wild-type (WT) controls. Systemic administration of telmisartan protected WT mice from lethal encephalitis caused by two different alphaviruses in a dose-dependent manner without altering virus replication or exerting any anti-inflammatory effects in the CNS. Infection triggered up-regulation of multiple Nox subunits in the CNS, while drug treatment inhibited local Nox activity, ROS production, and oxidative neuronal damage. Telmisartan proved ineffective in Nox-deficient mice, demonstrating that this enzyme is its main target in this experimental setting. Nox-derived ROS, likely arising from CNS myeloid cells triggered by AT1R signaling, are pathogenic during fatal alphavirus encephalitis in mice. Systemically administered telmisartan at non-hypotensive doses targets Nox activity in the CNS to exert a neuroprotective effect. Disruption of this pathway may have broader implications for the treatment of related infections as well as for other CNS diseases driven by oxidative injury.

Poster Presentations in Undergraduate Education and at Professional Meetings.

DTIC Science & Technology

1983-10-01

AD-Ri34 684 POSTER PRESENTATIONS IN UNDERGRADUATE EDUCATION AND fiT i/i PROFESSIONAL MEETINGS(U) AIR FORCE ACADEMY CO J T WIEBB ET AL- OCT 83 USAFA...USAFA-TR 83-17 4. TITLE (and Subtitle) S TYPE OF REPORT & PERIOD COVERED POSTER PRESENTATIONS IN UNDERGRADUATE EDUCATION AND AT PROFESSIONAL MEETINGS...19 r.EY WORDS (Continue on reverse side if necessary and Identify by block number) Poster , USAFA, technical writing, education 20 ABSTRACT (Continue on

Elevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling

PubMed Central

Zhao, Yingzi; Flavahan, Sheila; Leung, Susan W.; Xu, Aimin; Vanhoutte, Paul M.

2014-01-01

Experiments were performed to determine whether or not acute exposure to elevated pressure would disrupt endothelium-dependent dilatation by increasing local angiotensin II (ANG II) signaling. Vasomotor responses of mouse-isolated carotid arteries were analyzed in a pressure myograph at a control transmural pressure (PTM) of 80 mmHg. Acetylcholine-induced dilatation was reduced by endothelial denudation or by inhibition of nitric oxide synthase (NG-nitro-l-arginine methyl ester, 100 μM). Transient exposure to elevated PTM (150 mmHg, 180 min) inhibited dilatation to acetylcholine but did not affect responses to the nitric oxide donor diethylamine NONOate. Elevated PTM also increased endothelial reactive oxygen species, and the pressure-induced endothelial dysfunction was prevented by the direct antioxidant and NADPH oxidase inhibitor apocynin (100 μM). The increase in endothelial reactive oxygen species in response to elevated PTM was reduced by the ANG II type 1 receptor (AT1R) antagonists losartan (3 μM) or valsartan (1 μM). Indeed, elevated PTM caused marked expression of angiotensinogen, the precursor of ANG II. Inhibition of ANG II signaling, by blocking angiotensin-converting enzyme (1 μM perindoprilat or 10 μM captopril) or blocking AT1Rs prevented the impaired response to acetylcholine in arteries exposed to 150 mmHg but did not affect dilatation to the muscarinic agonist in arteries maintained at 80 mmHg. After the inhibition of ANG II, elevated pressure no longer impaired endothelial dilatation. In arteries treated with perindoprilat to inhibit endogenous formation of the peptide, exogenous ANG II (0.3 μM, 180 min) inhibited dilatation to acetylcholine. Therefore, elevated pressure rapidly impairs endothelium-dependent dilatation by causing ANG expression and enabling ANG II-dependent activation of AT1Rs. These processes may contribute to the pathogenesis of hypertension-induced vascular dysfunction and organ injury. PMID:25485905

Elevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling.

PubMed

Zhao, Yingzi; Flavahan, Sheila; Leung, Susan W; Xu, Aimin; Vanhoutte, Paul M; Flavahan, Nicholas A

2015-02-15

Experiments were performed to determine whether or not acute exposure to elevated pressure would disrupt endothelium-dependent dilatation by increasing local angiotensin II (ANG II) signaling. Vasomotor responses of mouse-isolated carotid arteries were analyzed in a pressure myograph at a control transmural pressure (PTM) of 80 mmHg. Acetylcholine-induced dilatation was reduced by endothelial denudation or by inhibition of nitric oxide synthase (NG-nitro-L-arginine methyl ester, 100 μM). Transient exposure to elevated PTM (150 mmHg, 180 min) inhibited dilatation to acetylcholine but did not affect responses to the nitric oxide donor diethylamine NONOate. Elevated PTM also increased endothelial reactive oxygen species, and the pressure-induced endothelial dysfunction was prevented by the direct antioxidant and NADPH oxidase inhibitor apocynin (100 μM). The increase in endothelial reactive oxygen species in response to elevated PTM was reduced by the ANG II type 1 receptor (AT1R) antagonists losartan (3 μM) or valsartan (1 μM). Indeed, elevated PTM caused marked expression of angiotensinogen, the precursor of ANG II. Inhibition of ANG II signaling, by blocking angiotensin-converting enzyme (1 μM perindoprilat or 10 μM captopril) or blocking AT1Rs prevented the impaired response to acetylcholine in arteries exposed to 150 mmHg but did not affect dilatation to the muscarinic agonist in arteries maintained at 80 mmHg. After the inhibition of ANG II, elevated pressure no longer impaired endothelial dilatation. In arteries treated with perindoprilat to inhibit endogenous formation of the peptide, exogenous ANG II (0.3 μM, 180 min) inhibited dilatation to acetylcholine. Therefore, elevated pressure rapidly impairs endothelium-dependent dilatation by causing ANG expression and enabling ANG II-dependent activation of AT1Rs. These processes may contribute to the pathogenesis of hypertension-induced vascular dysfunction and organ injury. Copyright © 2015 the American Physiological Society.

Epidemiological studies on salmonella in a certain area ("Walcheren project") III. The presence of salmonella in man, insects, seagulls and in foods, chopping-block scrapings from butcher's shops, effluent of sewage treatment plants and drains of butcher's shops.

PubMed

Edel, W; van Schothorst, M; van Leusden, F M; Kampelmacher, E H

1978-12-01

For a period of three months in a relatively small area (Walcheren), various materials (meat and meat products, insects, seagull droppings, chopping-block scrapings from butcher's shops, effluent of sewage treatment plants, drains from butcher's shops and stools of patients) were examined again for the presence of Salmonella as a continuation of previous investigations. As had been the case in previous studies, S. typhimurium (27.5%), S. panama (22.2%) and S. brandenburg (9.2%) were the three most frequently isolated serotypes. The three most frequently isolated phage types of S. typhimurium were II 505 (62.1%) II 502 (5.3%) and I 650 (4.2%). The serotypes and phage types were present in almost all the materials examined which again emphasizes the fact that there are contamination cycles of Salmonella. These studies show that the route of contamination divides in the butcher's shops. Salmonella organisms carried with the meat from the slaughter-house find their way into the drains on the one hand, and through meat and meat products, to the consumer on the other. Moreover, the high degree of contamination of effluent is not in accordance with the small number of cases of salmonellosis in man.

[Limits of cardiac functional adaptation in "top level" resistance athletes].

PubMed

Carù, B; Righetti, G; Bossi, M; Gerosa, C; Gazzotti, G; Maranetto, D

2001-02-01

Sports activity, particularly when performed at high level, provokes cardiovascular adjustments depending on the type of sport and on the level of the load. We evaluated 15 athletes from the Italian national team during a non-agonistic period of cross country skiing, with non-invasive tests including exercise test, color Doppler echocardiography, Holter monitoring, physical examination and standard rest electrocardiogram. Physical examination, rest electrocardiogram, exercise testing and echocardiography were all within the range of the expected values for this type of subjects. Holter monitoring recorded during the periods of agonistic activity revealed significant hypokinetic arrhythmias such as severe bradycardia, pauses, I and II degree atrioventricular blocks, and complete atrioventricular block in 2 cases; these features were not observed on Holter monitoring recorded during the non-agonistic period. The perfect health status of subjects and their racing results may bring about physiological functional adjustments, but these observations suggest the need for a follow-up to evaluate possible pathologic outcomes.

Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

PubMed Central

Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

2014-01-01

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

Electrical filtering in gerbil isolated type I semicircular canal hair cells

NASA Technical Reports Server (NTRS)

Rennie, K. J.; Ricci, A. J.; Correia, M. J.

1996-01-01

1. Membrane potential responses of dissociated gerbil type I semicircular canal hair cells to current injections in whole cell current-clamp have been measured. The input resistance of type I cells was 21.4 +/- 14.3 (SD) M omega, (n = 25). Around the zero-current potential (Vz = -66.6 +/- 9.3 mV, n = 25), pulsed current injections (from approximately -200 to 750 pA) produced only small-amplitude, pulse-like changes in membrane potential. 2. Injecting constant current to hyperpolarize the membrane to around -100 mV resulted in a approximately 10-fold increase in membrane resistance. Current pulses superimposed on this constant hyperpolarization produced larger and more complex membrane potential changes. Depolarizing currents > or = 200 pA caused a rapid transient peak voltage before a plateau. 3. Membrane voltage was able to faithfully follow sine-wave current injections around Vz over the range 1-1,000 Hz with < 25% attenuation at 1 kHz. A previously described K conductance, IKI, which is active at Vz, produces the low input resistance and frequency response. This was confirmed by pharmacologically blocking IKI. This conductance, present in type I cells but not type II hair cells, would appear to confer on type I cells a lower gain, but a much broader bandwidth at Vz, than seen in type II cells.

Trichostatin A inhibits radiation-induced epithelial-to-mesenchymal transition in the alveolar epithelial cells

PubMed Central

Nagarajan, Devipriya; Wang, Lei; Zhao, Weiling; Han, Xiaochen

2017-01-01

Radiation-induced pneumonitis and fibrosis are major complications following thoracic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue injury leading to organ fibrosis, including lung. Our previous studies have reported that radiation can induce EMT in the type II alveolar epithelial cells in both in vitro and in vivo. HDAC inhibitors are a new family of anti-cancer agents currently being used in several clinical trials. In addition to their intrinsic anti-tumor properties, HDAC inhibition is also important in other human diseases, including fibrosis and radiation-induced damage. In this study, we evaluated the effect of Trichostatin A (TSA), a HDAC inhibitor, on radiation-induced EMT in type II alveolar epithelial cells (RLE-6TN). Pre-treatment of RLE-6TN cells with TSA inhibited radiation-induced EMT-like morphological alterations including elevated protein level of α-SMA and Snail, reduction of E-cadherin expression, enhanced phosphorylation of GSK3β and ERK1/2, increased generation of ROS. Radiation enhanced the protein level of TGF-β1, which was blocked by N-acetylcysteine, an antioxidant. Treating cells with SB-431542, TGF-β1 type I receptor inhibitor, diminished radiation-induced alterations in the protein levels of p-GSK-3β, Snail-1 and α-SMA, suggesting a regulatory role of TGF-β1 in EMT. Pre-incubation of cells with TSA showed significant decrease in the level of TGF-β1 compared to radiation control. Collectively, these results demonstrate that i] radiation-induced EMT in RLE-6TN cells is mediated by ROS/MEK/ERK and ROS/TGF-β1 signaling pathways and ii] the inhibitory role of TSA in radiation-induced EMT appears to be due, at least in part, to its action of blocking ROS and TGF-β1 signaling. PMID:29254201

Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

PubMed Central

Otero, Miguel; Lago, Rocío; Lago, Francisca; Reino, Juan Jesús Gomez; Gualillo, Oreste

2005-01-01

The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and in human primary chondrocytes. This study indicates that leptin plays a proinflammatory role, in synergy with IL-1, by inducing NOS type II through a signalling pathway that involves JAK2, PI3K, MEK-1 and p38 kinase. PMID:15899045

Standardized Curriculum for Brick, Block, and Stonemasonry.

ERIC Educational Resources Information Center

Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

Standardized curricula are provided for two courses for the secondary vocational education program in Mississippi: brick, block, and stonemasonry I and II. The six units in brick, block, and stonemasonry I are as follows: orientation and leadership activities; safety; basic tools and equipment; masonry units; mortar; and wall layout. Brick, block,…

An Analysis of Instruction-Cached SIMD Computer Architecture

DTIC Science & Technology

1993-12-01

ASSEBLE SIMULATE SCHEDULE VERIFY :t og ... . .. ... V~JSRUCTONSFOR PECIIEDCOMPARE ASSEMBLEI SIMULATE Ift*U1II ~ ~ SCHEDULEIinw ;. & VERIFY...Cache to Place Blocks ................. 70 4.5.4 Step 4: Schedule Cache Blocks ............................. 70 4.5.5 Step 5: Store Cache Blocks...167 B.4 Scheduler .............................................. 167 B.4.1 Basic Block Definition

Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Instructor Guide.

ERIC Educational Resources Information Center

Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

This instructor guide together with a student guide comprise a set of curriculum materials on the criminal justice system. The instructor guide is a resource for planning and managing individualized, competency-based instruction in six major subject areas or blocks, which are further broken down into several units with some units having several…

Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques.

PubMed

Noda, Akihiro; Fushiki, Hiroshi; Murakami, Yoshihiro; Sasaki, Hiroshi; Miyoshi, Sosuke; Kakuta, Hirotoshi; Nishimura, Shintaro

2012-11-01

Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT(1)) receptor (AT(1)R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using (11)C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Three male rhesus macaques were bolus intravenously administered [(11)C]telmisartan either alone or as a mixture with unlabeled telmisartan (1mg/kg). Dynamic PET images were acquired for 95min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Telmisartan penetrated into the brain little but enough to block AT(1)R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT(1)R distribution was noted over the entire brain, even on tracer alone dosing. Telmisartan penetrated into the brain enough to block AT(1)R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs. Copyright © 2012 Elsevier Inc. All rights reserved.

Questioning the rule of thumb: can verbal tasks be administered during the CVLT-II delay interval?

PubMed

Williams, Bethany R; Donovick, Peter J

2008-09-01

In the manual for the California Verbal Learning Test - II (CVLT-II), the authors suggest that nonverbal, rather than verbal, tasks be administered during the delay interval between administrations of the Short- and Long-Delay Recall trials of this test. They contend that this method minimizes the retroactive interference produced by intervening tasks. The purpose of the current study was to compare the extent to which verbal and nonverbal intervening tasks produce retroactive interference on CVLT-II List A recall following the long-delay. Participants in the present study were 120 undergraduate students. All participants completed the CVLT-II, and were randomly assigned to a group in which they were administered either a verbal (WAIS-III Vocabulary or Peabody Picture Vocabulary Test - IIIB) or nonverbal (Raven's Standard Progressive Matrices or WAIS-III Block Design) intervening task during the long-delay interval of the CVLT-II. Statistical analyses revealed that regardless of the type of intervening task given, participants in all groups recalled the same number of words and produced a similar number of intrusions during the CVLT-II recall trials. This indicates that not all verbal tasks produce retroactive effects beyond those produced by nonverbal tasks.

Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.

PubMed

Tenenholz, T C; Rogowski, R S; Collins, J H; Blaustein, M P; Weber, D J

1997-03-11

PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A-type channels at much lower concentrations than does charybdotoxin.

A comparision of Twin-block and Forsus (FRD) functional appliance--a cephalometric study.

PubMed

Mahamad, Irfanulla Khan; Neela, Praveen Kumar; Mascarenhas, Rohan; Husain, Akhter

2012-01-01

The aim was to compare the effects of Twin-block & Forsus (FRD) functional appliances in the correction of Angles Class II division 1 malocclusions. Pre- and post-treatment lateral cephalograms of 25 patients who underwent treatment with twin block for the correction of class II div 1 were compared with 25 patients who underwent treatment with Forsus appliance. These were again compared with the pre follow up and post follow up lateral cephalograms of 25 patients who have not undergone any treatment during this period. All the 3 group patients were compared for skeletal, dental and soft tissue parameters. Cephalometric analysis revealed that both Twin-block & Forsus Fatigue Resistant Device (FRD) appliances stimulated mandibular growth. Statistically significant differences between the two groups were found. Twin-block patients showed statistically very high significant (p < 0.001) increase in mandibular length (6.02 mm) whereas Forsus appliance patients showed significant (p < 0.05) increase in mandibular length (1.6 mm) when compared with control group (0.3 mm). No significant restriction of maxillary growth was found in either of the two experimental groups when compared to control group. Significant increase in lower anterior facial height & posterior facial height was observed in both experimental groups in relation to control group. Significant reduction of overjet and overbite was observed in both experimental groups. Class I molar relationship and improvement in the soft tissue profile were achieved in both treatment groups compared with control group. Both Twin Block and Forsus were effective in the treatment of Class II Div 1 malocclusion. Class II correction with Twin-block is more due to mandibular skeletal and dentoalveolar changes whereas in Forsus, it is more due to dentoalveolar changes and less skeletal changes.

Adding a PECS II block for proximal arm arteriovenous access - a randomised study.

PubMed

Quek, K H; Low, E Y; Tan, Y R; Ong, A S C; Tang, T Y; Kam, J W; Kiew, A S C

2018-05-01

Brachial plexus block is often utilised for proximal arm arteriovenous access creation. However, the medial upper arm and axilla are often inadequately anaesthetised, requiring repeated, intraoperative local anaesthetic supplementation, or conversion into general anaesthesia. We hypothesised that the addition of a PECS II block would improve anaesthesia and analgesia for proximal arm arteriovenous access surgery. In this prospective, double-blinded, randomised proof-of-concept study, 36 consenting adults with end-stage renal disease aged between 21 and 90 years received either a combined supraclavicular and PECS II block (Group PECS, n = 18), or combined supraclavicular and sham block (Group SCB, n = 18) for proximal arm arteriovenous access surgery. Primary outcome was whether patients required intraoperative local anaesthetic supplementation by the surgeon. In Group PECS, 33.3% (6/18) needed local anaesthetic supplementation vs. 100% (18/18) in Group SCB. Group SCB had three times (RR 3.0, 95% CI 1.6-5.8; P < 0.001) the risk of requiring intraoperative local anaesthetic supplementation. Group PECS required lower volume of supplemental local anaesthetic compared to Group SCB (0.0 ml, IQR 0.0-6.3 ml vs. 15.0 ml, IQR 7.4-17.8 ml; P < 0.001). Group SCB had twice [RR 2.2, 95% CI 1.1-4.4; (P = 0.019)] the risk of needing additional sedation or analgesia. There were no significant differences between the groups with respect to postoperative visual analogue scale pain scores, time to first rescue analgesia or patient satisfaction. The results suggest that adding a PECS II block to a supraclavicular block improves regional anaesthesia for patients with end-stage renal disease undergoing proximal arm arteriovenous access surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports].

PubMed

Antonijević, Nabojsa; Stanojević, Milica; Perunicić, Jovan; Djokić, Milan; Miković, Danijla; Kovac, Mirjana; Miljić, Predrag; Milosević, Rajko; Terzić, Branka; Vasiljević, Zorana

2004-01-01

Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37 x 10(9)/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59 x 10(9)/l on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immuno-assay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of antithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

Vitamin K and cancer.

PubMed

Dahlberg, Sofia; Ede, Jacob; Schött, Ulf

2017-12-01

Subclinical vitamin K deficits refer to carboxylation defects of different types of vitamin K-dependent hepatic and extrahepatic so-called Gla proteins without prolongation of the prothrombin time. This condition has been reported in different clinical situations due to insufficient supply or malabsorption of vitamin K as well as drug interactions. This review discusses the effects of different vitamin K subspecies on tumour growth and the possible anti-tumour effects of increased vitamin K intake. Blocking carboxylation of vitamin K-dependent proteins with warfarin anticoagulation - what are the risks/benefits for carcinogenesis? Previous studies on both heparin and low molecular weight heparin blocking of the vitamin K-dependent factors X and II have shown tumour suppressive effects. Vitamin K has anti-inflammatory effects that could also impact carcinogenesis, but little data exists on this subject.

Apollo CSM Power Generation System Design Considerations, Failure Modes and Lessons Learned

NASA Technical Reports Server (NTRS)

Interbartolo, Michael

2009-01-01

The objectives of this slide presentation are to: review the basic design criteria for fuel cells (FC's), review design considerations during developmental phase that affected Block I and Block II vehicles, summarize the conditions that led to the failure of components in the FC's, and state the solution implemented for each failure. It reviews the location of the fuel cells, the fuel cell theory the design criteria going into development phase and coming from the development phase, failures and solutions of Block I and II, and the lessons learned.

SKYSINE-II procedure: calculation of the effects of structure design on neutron, primary gamma-ray and secondary gamma-ray dose rates in air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lampley, C.M.

1979-01-01

An updated version of the SKYSHINE Monte Carlo procedure has been developed. The new computer code, SKYSHINE-II, provides a substantial increase in versatility in that the program possesses the ability to address three types of point-isotropic radiation sources: (1) primary gamma rays, (2) neutrons, and (3) secondary gamma rays. In addition, the emitted radiation may now be characterized by an energy emission spectrum product of a new energy-dependent atmospheric transmission data base developed by Radiation Research Associates, Inc. for each of the three source types described above. Most of the computational options present in the original program have been retainedmore » in the new version. Hence, the SKYSHINE-II computer code provides a versatile and viable tool for the analysis of the radiation environment in the vicinity of a building structure containing radiation sources, situated within the confines of a nuclear power plant. This report describes many of the calculational methods employed within the SKYSHINE-II program. A brief description of the new data base is included. Utilization instructions for the program are provided for operation of the SKYSHINE-II code on the Brookhaven National Laboratory Central Scientific Computing Facility. A listing of the source decks, block data routines, and the new atmospheric transmission data base are provided in the appendices of the report.« less

Tracking Solar Type II Bursts with Space Based Radio Interferometers

NASA Astrophysics Data System (ADS)

Hegedus, Alexander M.; Kasper, Justin C.; Manchester, Ward B.

2018-06-01

The Earth’s Ionosphere limits radio measurements on its surface, blocking out any radiation below 10 MHz. Valuable insight into many astrophysical processes could be gained by having a radio interferometer in space to image the low frequency window for the first time. One application is observing type II bursts tracking solar energetic particle acceleration in Coronal Mass Ejections (CMEs). In this work we create a simulated data processing pipeline for several space based radio interferometer (SBRI) concepts and evaluate their performance in the task of localizing these type II bursts.Traditional radio astronomy software is hard coded to assume an Earth based array. To circumvent this, we manually calculate the antenna separations and insert them along with the simulated visibilities into a CASA MS file for analysis. To create the realest possible virtual input data, we take a 2-temperature MHD simulation of a CME event, superimpose realistic radio emission models from the CME-driven shock front, and propagate the signal through simulated SBRIs. We consider both probabilistic emission models derived from plasma parameters correlated with type II bursts, and analytical emission models using plasma emission wave interaction theory.One proposed SBRI is the pathfinder mission SunRISE, a 6 CubeSat interferometer to circle the Earth in a GEO graveyard orbit. We test simulated trajectories of SunRISE and image what the array recovers, comparing it to the virtual input. An interferometer on the lunar surface would be a stable alternative that avoids noise sources that affect orbiting arrays, namely the phase noise from positional uncertainty and atmospheric 10s-100s kHz noise. Using Digital Elevation Models from laser altimeter data, we test different sets of locations on the lunar surface to find near optimal configurations for tracking type II bursts far from the sun. Custom software is used to model the response of different array configurations over the lunar year, combining ephemerides of the sun and moon to correlate the virtual data. We analyze the pros and cons of all approaches and offer recommendations for SRBIs that track type II bursts.

Petrology and geochemistry of mafic magmatic rocks from the Sarve-Abad ophiolites (Kurdistan region, Iran): Evidence for interaction between MORB-type asthenosphere and OIB-type components in the southern Neo-Tethys Ocean

NASA Astrophysics Data System (ADS)

Saccani, Emilio; Allahyari, Khalil; Rahimzadeh, Bahman

2014-05-01

The Sarve-Abad (Sawlava) ophiolites crop out in the Main Zagros Thrust Zone and represent remnants of the Mesozoic southern Neo-Tethys Ocean that was located between the Arabian shield and Sanandaj-Sirjan continental block. They consist of several incomplete ophiolitic sequences including gabbroic bodies, a dyke complex, and pillow lava sequences. These rocks generally range from sub-alkaline to transitional character. Mineral chemistry and whole-rock geochemistry indicate that they have compositions akin to enriched-type mid-ocean ridge basalts (E-MORB) and plume-type MORB (P-MORB). Nonetheless, the different depletion degrees in heavy rare earth elements (HREE), which can be observed in both E-MORB like and P-MORB like rocks enable two main basic chemical types of rocks to be distinguished as Type-I and Type-II. Type-I rocks are strongly depleted in HREE (YbN < ~ 6), whereas Type-II rocks are moderately depleted in HREE (YbN > 9.0). Petrogenetic modeling shows that Type-I rocks originated from 7 to 16% polybaric partial melting of a MORB-type mantle source, which was significantly enriched by plume-type components. These rocks resulted from the mixing of variable fractions of melts generated in garnet-facies and the spinel-facies mantle. In contrast, Type-II rocks originated from 5 to 8% partial melting in the spinel-facies of a MORB-type source, which was moderately enriched by plume-type components. A possible tectono-magmatic model for the generation of the southern Neo-Tethys oceanic crust implies that the continental rift and subsequent oceanic spreading were associated with uprising of MORB-type asthenospheric mantle featuring plume-type component influences decreasing from deep to shallow mantle levels. These deep plume-type components were most likely inherited from Carboniferous mantle plume activity that was associated with the opening of Paleo-Tethys in the same area.

Apollo Block I Spacesuit Development and Apollo Block II Spacesuit Competition

NASA Technical Reports Server (NTRS)

McBarron, Jim

2013-01-01

Jim McBarron has over 40 years of experience with the U.S. Air Force pressure suit and NASA spacesuit development and operations. As a result of his experience, he shared his significant knowledge about the requirements and modifications made to the Gemini spacesuit, which were necessary to support the Apollo Block I Program. In addition, he provided an overview of the Apollo Block II Spacesuit competition test program conducted by the NASA Manned Spacecraft Center. Topics covered included the program's chronology; competition test program ground rules, scoring details, and final test results; and the implementation of resulting modifications to the Apollo Spacesuit Program. He concluded his presentation by identifying noteworthy lessons learned.

Electrical and Optical Characterization System for IR Photodetectors

DTIC Science & Technology

2015-10-12

is marked using the red circles. The newly purchased equipment includes a fast HgCdTe ( MCT ) detector and a 1064 nm pulse laser. The new fast MCT ...signal-to- noise ratio. Figure 1. The block diagram of the upgraded TRPL system. The detector and laser are newly purchased. The chopper and lock...type-II superlattices (T2SL) based infrared photodetectors. Ga-free InAs/InAsSb T2SLs offer great advantages for MWIR and LWIR laser and detector

Angiotensin II modulates salty and sweet taste sensitivities.

PubMed

Shigemura, Noriatsu; Iwata, Shusuke; Yasumatsu, Keiko; Ohkuri, Tadahiro; Horio, Nao; Sanematsu, Keisuke; Yoshida, Ryusuke; Margolskee, Robert F; Ninomiya, Yuzo

2013-04-10

Understanding the mechanisms underlying gustatory detection of dietary sodium is important for the prevention and treatment of hypertension. Here, we show that Angiotensin II (AngII), a major mediator of body fluid and sodium homeostasis, modulates salty and sweet taste sensitivities, and that this modulation critically influences ingestive behaviors in mice. Gustatory nerve recording demonstrated that AngII suppressed amiloride-sensitive taste responses to NaCl. Surprisingly, AngII also enhanced nerve responses to sweeteners, but had no effect on responses to KCl, sour, bitter, or umami tastants. These effects of AngII on nerve responses were blocked by the angiotensin II type 1 receptor (AT1) antagonist CV11974. In behavioral tests, CV11974 treatment reduced the stimulated high licking rate to NaCl and sweeteners in water-restricted mice with elevated plasma AngII levels. In taste cells AT1 proteins were coexpressed with αENaC (epithelial sodium channel α-subunit, an amiloride-sensitive salt taste receptor) or T1r3 (a sweet taste receptor component). These results suggest that the taste organ is a peripheral target of AngII. The specific reduction of amiloride-sensitive salt taste sensitivity by AngII may contribute to increased sodium intake. Furthermore, AngII may contribute to increased energy intake by enhancing sweet responses. The linkage between salty and sweet preferences via AngII signaling may optimize sodium and calorie intakes.

Searching phase II enzymes inducers, from Michael acceptor-[1,2]dithiolethione hybrids, as cancer chemopreventive agents.

PubMed

Couto, Marcos; de Ovalle, Stefani; Cabrera, Mauricio; Cerecetto, Hugo; González, Mercedes

2015-01-01

Cancer chemoprevention involves the carcinogenic process prevention, delay or reverse by the administration of chemopreventive agents, which are able to suppress or block the carcinogen metabolic activation/formation. The increased activity of phase II detoxification enzymes such as quinone-reductase (QR) and glutation-S-transferase (GST) correlates with the protection against chemically-induced carcinogenesis. It has been shown that synthetic chalcones and 3H-[1,2]-dithiole-3-thiones promote expression of genes involved in chemoprevention. Herein, the induction of phase II enzymes by designed Michael acceptor-dithiolethione hybrids was studied. Hybrids 5 and 7 displayed the induction of quinone-reductase and glutation-S-transferase in vitro in the same order on the wild-type mouse-hepatoma Hepa 1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BPrc1 cells indicating that 7 displays the best chemopreventive potential.

Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

PubMed Central

Mhanna, Rami; Kashyap, Aditya; Palazzolo, Gemma; Vallmajo-Martin, Queralt; Becher, Jana; Möller, Stephanie; Schnabelrauch, Matthias

2014-01-01

The loss of expression of chondrogenic markers during monolayer expansion remains a stumbling block for cell-based treatment of cartilage lesions. Here, we introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that induces cell proliferation while maintaining the chondrogenic phenotype of encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates by incubation with sulfur trioxide–pyridine complex (SO3/pyridine), yielding a sulfated material cross-linkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared with alginate (p=0.038). Blocking beta1 integrins in chondrocytes within alginate sulfate hydrogels significantly inhibited proliferation (p=0.002). Sulfated alginate increased the RhoA activity of chondrocytes compared with unmodified alginate, an increase that was blocked by β1 blocking antibodies (p=0.017). Expression and synthesis of type II collagen, type I collagen, and proteoglycan was not significantly affected by the encapsulation material evidenced by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in culture, whereas the unmodified alginate samples remained translucent. In conclusion, alginate sulfate provides a three dimensional microenvironment that promotes both chondrocyte proliferation and maintenance of the chondrogenic phenotype and represents an important advance for chondrocyte-based cartilage repair therapies providing a material in which cell expansion can be done in situ. PMID:24320935

18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

PubMed Central

Du, Yi-mei; Xia, Cheng-kun; Zhao, Ning; Dong, Qian; Lei, Ming; Xia, Jia-hong

2012-01-01

Aim: To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na+ current, HERG and Kv1.5 channel currents. Methods: Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant ΔKPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents. Results: Superfusion of 18β-glycyrrhetinic acid (18β-GA, 1–100 μmol/L) blocked both the peak current (INa,P) and late current (INa,L) generated by WT and ΔKPQ Nav1.5 channels in a concentration-dependent manner, while 18α-glycyrrhetinic acid (18α-GA) at the same concentrations had no effects. 18β-GA preferentially blocked INa,L (IC50=37.2±14.4 μmol/L) to INa,P (IC50=100.4±11.2 μmol/L) generated by ΔKPQ Nav1.5 channels. In human atrial myocytes, 18β-GA (30 μmol/L) inhibited 47% of INa,P and 87% of INa,L induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of 18β-GA (100 μmol/L) had no effects on HERG and Kv1.5 channel currents. Conclusion: 18β-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels. PMID:22609834

KSHV LANA inhibits TGF-β signaling through epigenetic silencing of the TGF-β type II receptor

PubMed Central

Di Bartolo, Daniel L.; Cannon, Mark; Liu, Yi-Fang; Renne, Rolf; Chadburn, Amy; Boshoff, Chris

2008-01-01

Signaling through the transforming growth factor–β (TGF-β) pathway results in growth inhibition and induction of apoptosis in various cell types. We show that this pathway is blocked in Kaposi sarcoma herpesvirus (KSHV)–infected primary effusion lymphoma through down-regulation of the TGF-β type II receptor (TβRII) by epigenetic mechanisms. Our data also suggest that KSHV infection may result in lower expression of TβRII in Kaposi sarcoma and multicentric Castleman disease. KSHV-encoded LANA associates with the promoter of TβRII and leads to its methylation and to the deacetylation of proximal histones. Reestablishment of signaling through this pathway reduces viability of these cells, inferring that KSHV-mediated blockage of TGF-β signaling plays a role in the establishment and progression of KSHV-associated neoplasia. These data suggest a mechanism whereby KSHV evades both the antiproliferative effects of TGF-β signaling by silencing TβRII gene expression and immune recognition by suppressing TGF-β–responsive immune cells through the elevated secretion of TGF-β1. PMID:18199825

The Effect of Estradiol on the Growth Plate Chondrocytes of Limb and Spine from Postnatal Mice in vitro: The Role of Estrogen-Receptor and Estradiol Concentration.

PubMed

Shi, Sheng; Zheng, Shuang; Li, Xin-Feng; Liu, Zu-De

2017-01-01

Objectives: Skeletal development is a complex process. Little is known about the different response of limb or spine growth plate chondrocytes (LGP or SGP) to the estrogen level and the role of estrogen receptor (ER) during postnatal stage. Methods: LGP and SGP chondrocytes were isolated from 50 one-week mice and treated with different concentrations of 17β-estradiol. Cell viability was measured by cell counting kit-8 (CCK-8). The expression of collagen II and X were evaluated by real-time PCR and Western blotting. Then, the response of LGP or SGP chondrocyte after with or without estradiol and specific ER antagonists to block the effect of ERs were also measured by Western blotting and immunofluorescence. Results: Estradiol promoted the chondrogensis of the chondrocytes in vitro and achieved the maximal expression of type II collagen at the dose of 10 -7 M. Additionally, the regulatory effect of estradiol on the chondrogenesis can be mainly relied on ERα. The LGP chondrocytes were more sensitive to the estradiol treatment than SGP in the expression of type II collagen. Conclusions: Estrogen at a pharmacological concentration (10 -7 M) could stimulate the maximal production of type II collagen in the growth plate chondrocytes in vitro, which exerts its activity mainly through ERα in the chondrogenesis. Furthermore, the LGP chondrocytes were more sensitive to the estradiol treatment than SGP in the chondrogenesis.

Cephalomteric changes in airway dimensions with twin block therapy in growing Class II patients

PubMed Central

Vinoth, Santhana Krishnan; Thomas, Ashwin Varghese; Nethravathy, Ramya

2013-01-01

Introduction: Myofunctional appliances are commonly used for correction of skeletal Class II malrelationship. These appliances influence craniofacial and nasopharyngeal dimensions. Objectives: The present study was done to evaluate changes in airway with twin block therapy. Materials and Methods: Cephalometric assessment of airway was done in 25 growing children in the age group of 11-13 years with Class II skeletal pattern. All the patients were treated with twin block appliance. Pre and post treatment lateral cephalograms were taken to evaluate the changes in different airway and craniofacial dimensions during the treatment period. The average treatment duration was 14.5 months. Results: Airway: A significant increase was observed in upper and lower pharyngeal width and area of bony nasopharynx. Craniofacial dimension: There was a significant increase in effective mandibular length, ramal length and mandibular plane angle. There was an increase in SNB angle, which resulted in decreased ANB angle. Conclusion: There was a definite improvement in airway dimension following twin block therapy PMID:23946570

Predictors of favorable soft tissue profile outcomes following Class II Twin-block treatment.

PubMed

Kim, Ji-Eun; Mah, Su-Jung; Kim, Tae-Woo; Kim, Su-Jung; Park, Ki-Ho; Kang, Yoon-Goo

2018-01-01

The aim of this study was to determine cephalometric factors that help predict favorable soft-tissue profile outcomes following treatment with the Class II Twin-block appliance. Pre- and post-treatment lateral cephalograms of 45 patients treated with the Class II Twin-block appliance were retrospectively analyzed. Profile silhouettes were drawn from the cephalograms and evaluated by three orthodontists in order to determine the extent of improvement. Samples were divided into a favorable group (upper 30% of visual analogue scale [VAS] scores, n = 14) and an unfavorable group (lower 30% of VAS scores, n = 14). Skeletal and soft-tissue measurements were performed on the cephalograms and an intergroup comparison was conducted. An independent t -test revealed that the following pre-treatment values were lower in the favorable group compared to the unfavorable group: lower incisor to mandibular plane angle, lower incisor to pogonion distance, point A-nasion-point B angle, sella-nasion line (SN) to maxillary plane angle, SN to mandibular plane angle, gonial angle, and symphysis inclination. The favorable group had a larger incisor inclination to occlusal plane. Moreover, the favorable group showed larger post-treatment changes in gonial angle, B point projection, and pogonion projection than did the unfavorable group. Class II malocclusion patients with a low divergent skeletal pattern and reduced lower incisor protrusions are likely to show more improvement in soft-tissue profile outcomes following Class II Twin-block treatment.

Homology modeling, binding site identification and docking study of human angiotensin II type I (Ang II-AT1) receptor.

PubMed

Vyas, Vivek K; Ghate, Manjunath; Patel, Kinjal; Qureshi, Gulamnizami; Shah, Surmil

2015-08-01

Ang II-AT1 receptors play an important role in mediating virtually all of the physiological actions of Ang II. Several drugs (SARTANs) are available, which can block the AT1 receptor effectively and lower the blood pressure in the patients with hypertension. Currently, there is no experimental Ang II-AT1 structure available; therefore, in this study we modeled Ang II-AT1 receptor structure using homology modeling followed by identification and characterization of binding sites and thereby assessing druggability of the receptor. Homology models were constructed using MODELLER and I-TASSER server, refined and validated using PROCHECK in which 96.9% of 318 residues were present in the favoured regions of the Ramachandran plots. Various Ang II-AT1 receptor antagonist drugs are available in the market as antihypertensive drug, so we have performed docking study with the binding site prediction algorithms to predict different binding pockets on the modeled proteins. The identification of 3D structures and binding sites for various known drugs will guide us for the structure-based drug design of novel compounds as Ang II-AT1 receptor antagonists for the treatment of hypertension. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Heavy Duty Mechanics Apprenticeship Training, Module One. Volume II.

ERIC Educational Resources Information Center

Batchelor, Leslie A.; Abercrombie, Richard, Ed.

This training manual, the second of two volumes, comprises the final three blocks in a nine-block in-service training course for apprentices working in heavy duty mechanics. Addressed in the individual blocks included in this volume are engines, basic electricity, and winches. Each block contains a section on parts theory that gives the purpose,…

Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed

Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiacmore » fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen formation. ► Aspirin decreases the transcription of angiotensin II type 1 receptor by inhibiting NADPH oxidase–NF-κB pathway. ► The inhibition of angiotensin II type 1 receptor expression may be the basis for reduction in fibroblast growth and collagen formation. ► The effects of aspirin appear to be mediated via its salicylate moiety.« less

Theory of post-block 2 VLBI observable extraction

NASA Technical Reports Server (NTRS)

Lowe, Stephen T.

1992-01-01

The algorithms used in the post-Block II fringe-fitting software called 'Fit' are described. The steps needed to derive the very long baseline interferometry (VLBI) charged-particle corrected group delay, phase delay rate, and phase delay (the latter without resolving cycle ambiguities) are presented beginning with the set of complex fringe phasors as a function of observation frequency and time. The set of complex phasors is obtained from the JPL/CIT Block II correlator. The output of Fit is the set of charged-particle corrected observables (along with ancillary information) in a form amenable to the software program 'Modest.'

PHISICS/RELAP5-3D RESULTS FOR EXERCISES II-1 AND II-2 OF THE OECD/NEA MHTGR-350 BENCHMARK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strydom, Gerhard

2016-03-01

The Idaho National Laboratory (INL) Advanced Reactor Technologies (ART) High-Temperature Gas-Cooled Reactor (HTGR) Methods group currently leads the Modular High-Temperature Gas-Cooled Reactor (MHTGR) 350 benchmark. The benchmark consists of a set of lattice-depletion, steady-state, and transient problems that can be used by HTGR simulation groups to assess the performance of their code suites. The paper summarizes the results obtained for the first two transient exercises defined for Phase II of the benchmark. The Parallel and Highly Innovative Simulation for INL Code System (PHISICS), coupled with the INL system code RELAP5-3D, was used to generate the results for the Depressurized Conductionmore » Cooldown (DCC) (exercise II-1a) and Pressurized Conduction Cooldown (PCC) (exercise II-2) transients. These exercises require the time-dependent simulation of coupled neutronics and thermal-hydraulics phenomena, and utilize the steady-state solution previously obtained for exercise I-3 of Phase I. This paper also includes a comparison of the benchmark results obtained with a traditional system code “ring” model against a more detailed “block” model that include kinetics feedback on an individual block level and thermal feedbacks on a triangular sub-mesh. The higher spatial fidelity that can be obtained by the block model is illustrated with comparisons of the maximum fuel temperatures, especially in the case of natural convection conditions that dominate the DCC and PCC events. Differences up to 125 K (or 10%) were observed between the ring and block model predictions of the DCC transient, mostly due to the block model’s capability of tracking individual block decay powers and more detailed helium flow distributions. In general, the block model only required DCC and PCC calculation times twice as long as the ring models, and it therefore seems that the additional development and calculation time required for the block model could be worth the gain that can be obtained in the spatial resolution« less

Interactions among DIV voltage-sensor movement, fast inactivation, and resurgent Na current induced by the NaVβ4 open-channel blocking peptide

PubMed Central

Lewis, Amanda H.

2013-01-01

Resurgent Na current flows as voltage-gated Na channels recover through open states from block by an endogenous open-channel blocking protein, such as the NaVβ4 subunit. The open-channel blocker and fast-inactivation gate apparently compete directly, as slowing the onset of fast inactivation increases resurgent currents by favoring binding of the blocker. Here, we tested whether open-channel block is also sensitive to deployment of the DIV voltage sensor, which facilitates fast inactivation. We expressed NaV1.4 channels in HEK293t cells and assessed block by a free peptide replicating the cytoplasmic tail of NaVβ4 (the “β4 peptide”). Macroscopic fast inactivation was disrupted by mutations of DIS6 (L443C/A444W; “CW” channels), which reduce fast-inactivation gate binding, and/or by the site-3 toxin ATX-II, which interferes with DIV movement. In wild-type channels, the β4 peptide competed poorly with fast inactivation, but block was enhanced by ATX. With the CW mutation, large peptide-induced resurgent currents were present even without ATX, consistent with increased open-channel block upon depolarization and slower deactivation after blocker unbinding upon repolarization. The addition of ATX greatly increased transient current amplitudes and further enlarged resurgent currents, suggesting that pore access by the blocker is actually decreased by full deployment of the DIV voltage sensor. ATX accelerated recovery from block at hyperpolarized potentials, however, suggesting that the peptide unbinds more readily when DIV voltage-sensor deployment is disrupted. These results are consistent with two open states in Na channels, dependent on the DIV voltage-sensor position, which differ in affinity for the blocking protein. PMID:23940261

The expression and function of cathepsin E in dendritic cells.

PubMed

Chain, Benjamin M; Free, Paul; Medd, Patrick; Swetman, Claire; Tabor, Alethea B; Terrazzini, Nadia

2005-02-15

Cathepsin E is an aspartic proteinase that has been implicated in Ag processing within the class II MHC pathway. In this study, we document the presence of cathepsin E message and protein in human myeloid dendritic cells, the preeminent APCs of the immune system. Cathepsin E is found in a perinuclear compartment, which is likely to form part of the endoplasmic reticulum, and also a peripheral compartment just beneath the cell membrane, with a similar distribution to that of Texas Red-dextran within 2 min of endocytosis. To investigate the function of cathepsin E in processing, a new soluble targeted inhibitor was synthesized by linking the microbial aspartic proteinase inhibitor pepstatin to mannosylated BSA via a cleavable disulfide linker. This inhibitor was shown to block cathepsin D/E activity in cell-free assays and within dendritic cells. The inhibitor blocked the ability of dendritic cells from wild-type as well as cathepsin D-deficient mice to present intact OVA, but not an OVA-derived peptide, to cognate T cells. The data therefore support the hypothesis that cathepsin E has an important nonredundant role in the class II MHC Ag processing pathway within dendritic cells.

Ligament flow during drop-on-demand inkjet printing of bioink containing living cells

NASA Astrophysics Data System (ADS)

Zhang, Mengyun; Krishnamoorthy, Srikumar; Song, Hongtao; Zhang, Zhengyi; Xu, Changxue

2017-03-01

Organ printing utilizes tissue spheroids or filaments as building blocks to fabricate three-dimensional (3D) functional tissues and organs based on a layer-by-layer manufacturing mechanism. These fabricated tissues and organs are envisioned as alternatives to replace the damaged human tissues and organs, which is emerging as a promising solution to solve the organ donor shortage problem being faced all over the world. Inkjetting, one of the key technologies in organ printing, has been widely developed because of its moderate fabrication cost, good process controllability, and scale-up potentials. There are several key steps towards inkjet-based organ printing: generation of droplets from bioink, fabrication of 3D cellular structures, and post-printing tissue fusion and maturation. The droplet formation process is the first step, affecting the overall feasibility of the envisioned organ printing technology. This paper focuses on the ligament flow of the droplet formation process during inkjet printing of bioink containing living cells and its corresponding effect on post-printing cell viability and cell distribution. It is found that (1) two types of ligament flow are observed: at 30 V (Type I), the ligament flow has two different directions at the locations near the nozzle orifice and the forming droplet; at 60 V (Type II), the ligament flow directions are the same at both locations; (2) compared to Type II, fewer cells are ejected into the primary droplets in Type I, because some cells move back into the nozzle driven by the ligament flow in the positive z direction; and (3) cell viability in both Type I and Type II is around 90% without a significant difference. The resulting knowledge will benefit precise control of printing dynamics during inkjet printing of viscoelastic bioink for 3D biofabrication applications.

Generating global network structures by triad types

PubMed Central

Ferligoj, Anuška; Žiberna, Aleš

2018-01-01

This paper addresses the question of whether one can generate networks with a given global structure (defined by selected blockmodels, i.e., cohesive, core-periphery, hierarchical, and transitivity), considering only different types of triads. Two methods are used to generate networks: (i) the newly proposed method of relocating links; and (ii) the Monte Carlo Multi Chain algorithm implemented in the ergm package in R. Most of the selected blockmodel types can be generated by considering all types of triads. The selection of only a subset of triads can improve the generated networks’ blockmodel structure. Yet, in the case of a hierarchical blockmodel without complete blocks on the diagonal, additional local structures are needed to achieve the desired global structure of generated networks. This shows that blockmodels can emerge based only on local processes that do not take attributes into account. PMID:29847563

A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia.

PubMed

Yağan, Özgür; Taş, Nilay; Küçük, Ahmet; Hancı, Volkan

2016-01-01

The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mg mL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia].

PubMed

Yağan, Özgür; Taş, Nilay; Küçük, Ahmet; Hancı, Volkan

2016-01-01

The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mgmL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II.

PubMed

Steurer, Barbara; Marteijn, Jurgen A

2017-10-27

The faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The stalling of RNAP2 on a transcription-blocking lesion triggers a series of highly regulated events, including RNAP2 processing to make the lesion accessible for DNA repair, R-loop-mediated DNA damage signaling, and the initiation of transcription-coupled DNA repair. The correct execution and coordination of these processes is vital for resuming transcription following the successful repair of transcription-blocking lesions. Here, we outline recent insights into the molecular consequences of RNAP2 stalling on transcription-blocking DNA lesions and how these lesions are resolved to restore mRNA synthesis. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effect of local anesthetic dilution on the onset time and duration of double-injection sciatic nerve block: a prospective, randomized, blinded evaluation.

PubMed

Cappelleri, Gianluca; Ambrosoli, Andrea Luigi; Turconi, Stefania; Gemma, Marco; Ricci, Erika Basso; Cornaggia, Gabriele

2014-08-01

Among the various factors influencing the success rate, onset time, and duration of peripheral nerve blocks, the role of local anesthetics concentration remains uncertain. In this prospective, randomized, single-blinded study, we evaluated whether varying the dilution of a fixed dose of mepivacaine solution influenced onset time and duration of sciatic nerve block. Ninety ASA physical status I to II patients scheduled for foot surgery were randomly allocated to receive a double-injection Labat sciatic nerve block with 12 mL mepivacaine 2% (group concentration I = 45 patients) or 24 mL of mepivacaine 1% (group volume II = 45 patients). The nerve stimulator was initially set at 2 Hz, 0.1 millisecond, 1 mA. The total amount of local anesthetic (240 mg) was kept constant and equally divided between the peroneal and tibial nerves. All patients also received an ultrasound-guided popliteal sciatic nerve catheter for postoperative analgesia. Times to readiness for surgery, performance, and offset of local anesthetic were recorded. Our primary end point was to determine a possible difference in offset time between groups. Continuous variables were expressed as median (IQR) and compared with the Wilcoxon-Mann-Whitney U test; WMWodds are reported together with their 95% confidence interval. The overall success rate of sciatic nerve block was 99%. Time of performance was shorter in group I, 120 seconds (90-150 seconds), than that in group II, 150 seconds (120-180 seconds) (P = 0.0048; WMWodds 2.26 [1.35-4.34]). The onset time of sensory and motor sciatic nerve block was 4 minutes (2-9 minutes) in group I and 6 minutes (4-10 minutes) in group II (P = 0.41; WMWodds 1.21 [0.77-1.95]), while the duration of sensory block was 235 minutes (203-250 minutes) in group I, and 240 minutes (218-247 minutes) in group II respectively (P = 0.51; WMWodds 1.20 [0.69-2.16]). We found no evidence that varying volume and concentration while maintaining a fixed total dose of mepivacaine alters the onset time and duration of double-injection sciatic nerve block. Considering our WMWodds results, possible differences in onset time and duration comparable to differences in the performance time between groups cannot be excluded.

Ore genesis of the Wusihe carbonate-hosted Zn-Pb deposit in the Dadu River Valley district, Yangtze Block, SW China: evidence from ore geology, S-Pb isotopes, and sphalerite Rb-Sr dating

NASA Astrophysics Data System (ADS)

Xiong, Suo-Fei; Gong, Yong-Jun; Jiang, Shao-Yong; Zhang, Xiao-Jing; Li, Qian; Zeng, Guo-Ping

2018-01-01

The Wusihe carbonate-hosted Zn-Pb deposit (3.7 Mt. Zn + Pb at a grade of 8.6% Zn and 2.0% Pb) is the largest deposit in the Dadu River Valley district of the Sichuan-Yunnan-Guizhou metallogenic province of southwest China. Three types of orebodies occur: (1) stratiform, banded and lamellar, within dolomite of the Neoproterozoic Dengying Formation; (2) vein type; and (3) breccia type. Four stages of mineralization are distinguished: (i) pyrite stage, (ii) pyrite-pyrrhotite-galena-sphalerite-bitumen stage, (iii) sphalerite-galena stage, and (iv) bitumen-calcite stage. Sphalerite and galena from stages II and III show δ34S ranges from +7.1 to +9.7‰ and +9.1 to +13.1‰, respectively. High-precision in situ lead isotope analyses of sulfides show 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb ratios of 37.938 to 38.336, 15.579 to 15.682, and 17.951 to 18.195, respectively, which suggest a mixing of lead from the basement and the host rocks. Rb-Sr isotope analyses for six sphalerite samples of stage II yielded an isochron age of 411 ± 10 Ma (MSWD = 1.4). Combining all available ore geology and geochemical data, together with fluid inclusion data reported previously, we suggest that the Wusihe deposit is a Mississippi Valley-type (MVT) deposit.

The Effect of Rectus Sheath Block as a Supplement of General Anesthesia on Postoperative Analgesia in Adult Patient Undergoing Umbilical Hernia Repair.

PubMed

Kartalov, Andrijan; Jankulovski, Nikola; Kuzmanovska, Biljana; Zdravkovska, Milka; Shosholcheva, Mirjana; Tolevska, Marija; Naumovski, Filip; Srceva, Marija; Petrusheva, Aleksandra Panovska; Selmani, Rexhep; Sivevski, Atanas

2017-12-01

Ultrasound guided rectus sheath block can block the ventral rami of the 7th to 12th thoracolumbar nerves by injection of local anesthetic into the space between the rectus muscle and posterior rectus sheath. The aim of this randomized double-blind study was to evaluate the analgesic effect of the bilateral ultrasound guided rectus sheath block as supplement of general anesthesia on patents undergoing elective umbilical hernia repair. After the hospital ethics committee approval, 60 (ASA I-II) adult patients scheduled for umbilical hernia repair were included in this study. The group I (n=30) patents received only general anesthesia. In the group II (n = 30) patents after induction of general anesthesia received a bilateral ultrasound guided rectus sheath block with 40 ml of 0.25% bupivacaine. In this study we assessed demographic and clinical characteristics, pain score - VAS at rest at 2, 4, 6, 12 and 24 hours after operation and total analgesic consumption of morphine dose over 24-hours. There were statistically significant differences in VAS scores between the groups I and II at all postoperative time points - 2hr, 4 hr, 6 hr, 12 hr and 24 hr. (P < 0.00001). The cumulative 24 hours morphine consumption after the operation was significantly lower in the group II (mean = 3.73 ± 1. 41) than the group I (mean = 8.76 ± 2.41). This difference was statistically significant (p = 0.00076). The ultrasound guided rectus sheath block used for umbilical hernia repair could reduce postoperative pain scores and the amount of morphine consumption in 24 hours postoperative period.

AT1 receptor-mediated uptake of angiotensin II and NHE-3 expression in proximal tubule cells through a microtubule-dependent endocytic pathway.

PubMed

Li, Xiao C; Hopfer, Ulrich; Zhuo, Jia L

2009-11-01

Angiotensin II (ANG II) is taken up by proximal tubule (PT) cells via AT1 (AT1a) receptor-mediated endocytosis, but the underlying cellular mechanisms remain poorly understood. The present study tested the hypothesis that the microtubule- rather than the clathrin-dependent endocytic pathway regulates AT1-mediated uptake of ANG II and ANG II-induced sodium and hydrogen exchanger-3 (NHE-3) expression in PT cells. The expression of AT1 receptors, clathrin light (LC) and heavy chain (HC) proteins, and type 1 microtubule-associated proteins (MAPs; MAP-1A and MAP-1B) in PT cells were knocked down by their respective small interfering (si) RNAs before AT1-mediated FITC-ANG II uptake and ANG II-induced NHE-3 expression were studied. AT1 siRNAs inhibited AT1 expression and blocked ANG II-induced NHE-3 expression in PT cells, as expected (P < 0.01). Clathrin LC or HC siRNAs knocked down their respective proteins by approximately 90% with a peak response at 24 h, and blocked the clathrin-dependent uptake of Alexa Fluor 594-transferrin (P < 0.01). However, neither LC nor HC siRNAs inhibited AT1-mediated uptake of FITC-ANG II or affected ANG II-induced NHE-3 expression. MAP-1A or MAP-1B siRNAs markedly knocked down MAP-1A or MAP-1B proteins in a time-dependent manner with peak inhibitions at 48 h (>76.8%, P < 0.01). MAP protein knockdown resulted in approximately 52% decreases in AT1-mediated FITC-ANG II uptake and approximately 66% decreases in ANG II-induced NHE-3 expression (P < 0.01). These effects were associated with threefold decreases in ANG II-induced MAP kinases ERK 1/2 activation (P < 0.01), but not with altered AT1 expression or clathrin-dependent transferrin uptake. Both losartan and AT1a receptor deletion in mouse PT cells completely abolished the effects of MAP-1A knockdown on ANG II-induced NHE-3 expression and activation of MAP kinases ERK1/2. Our findings suggest that the alternative microtubule-dependent endocytic pathway, rather than the canonical clathrin-dependent pathway, plays an important role in AT1 (AT1a)-mediated uptake of extracellular ANG II and ANG II-induced NHE-3 expression in PT cells.

Overexpression of angiotensin II type 2 receptor promotes apoptosis and impairs insulin secretion in rat insulinoma cells.

PubMed

Liu, Min; Jing, Danqing; Wang, Yan; Liu, Yu; Yin, Shinan

2015-02-01

Angiotensin II (Ang II), the major effector hormone of renin-angiotensin system, acts as a promoter of insulin resistance and diabetes mellitus type 2 pathogenesis. Activation of Ang II type 2 receptor (AT2R) has been examined as a potential therapeutic strategy. However, there are conflicting findings regarding the role of AT2R. In the current study, we evaluated the effects of overexpressing AT2R by viral vector transduction on the apoptosis and function of pancreatic β-islet cells. The rat insulinoma cell line, INS-1, was transduced with a recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP). AT2R overexpression resulted in significantly reduced cell viability and subsequently impaired glucose-stimulated insulin secretion (GSIS) function in INS-1 cells. Down-regulated expressions of GSIS pathway components, insulin, glucose transporter 2, and glucokinase were associated with AT2R overexpression. Further analysis determined that overexpression of AT2R induced G1-phase cell cycle arrest and Ang II-independent apoptotic cell death as indicated by increased Annexin V staining. To understand the apoptosis signaling triggered by AT2R overexpression, levels of caspase proteins were measured. Overexpression of AT2R significantly induced caspase-8, caspase-9, and caspase-3 cleavage, and decreased Bcl-2, pAkt, and pERK expression levels. AT2R-induced cell apoptosis was successfully blocked by the caspase inhibitor Z-VAD-FMK. Our findings suggested that AT2R overexpression triggers the apoptosis of INS-1 cells and dysfunction in insulin secretion. In conclusion, more careful design and consideration are required when applying AT2R-related therapies in treating diabetes.

Deletion of angiotensin II type 1 receptor gene or scavenge of superoxide prevents chronic alcohol-induced aortic damage and remodelling.

PubMed

Bai, Yang; Tan, Yi; Wang, Bo; Miao, Xiao; Chen, Qiang; Zheng, Yang; Cai, Lu

2012-10-01

To investigate whether chronic alcohol consumption induces vascular injury via angiotensin II (Ang II) type 1 (AT1) receptor-dependent superoxide generation, male transgenic mice with knockout of AT1 gene (AT1-KO) and age-matched wild-type (WT) C57BL/6 mice were pair-fed a modified Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 2 months. Ethanol content (%, W/V) in the diet was 4.8 (34% of total calories) at initiation, and gradually increased up to 5.4 (38% of total calories). For some WT mice with and without alcohol treatment, superoxide dismutase mimetic (MnTMPyP) was given simultaneously by intraperitoneal injection at 5 mg/kg body weight daily for 2 months. At the end of studies, aortas were harvested for histopathological and immunohistochemical examination. Significant increases in the wall thickness and structural disarrangement of aorta were found in alcohol group, along with significant increases in aortic oxidative and/or nitrosative damage, expressions of NADPH oxidases (NOXs), inflammatory response, cell death and proliferation, and remodelling (fibrosis). However, these pathological changes were completely attenuated in alcohol-treated AT1-KO mice or in alcohol-treated WT mice that were also simultaneously treated with MnTMPyP for 2 months. These results suggest that chronic alcohol consumption may activate NOX via Ang II/AT1 receptor, to generate superoxide and associated peroxynitrite that in turn causes aortic nitrosative damage, inflammation, cell death and proliferation, and remodelling. Therefore, blocking Ang II/AT1 system or scavenging superoxide may become a potential preventive and/therapeutic approach to alcoholic vascular damage. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Block by Block: Neighborhoods and Public Policy on Chicago's West Side. Historical Studies of Urban America

ERIC Educational Resources Information Center

Seligman, Amanda I.

2005-01-01

In the decades following World War II, cities across the United States saw an influx of African American families into otherwise homogeneously white areas. This racial transformation of urban neighborhoods led many whites to migrate to the suburbs, producing the phenomenon commonly known as white flight. In "Block by Block," Amanda I.…

26 CFR 1.883-2 - Treatment of publicly-traded corporations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... closely-held block of stock. (ii) Exception. Paragraph (d)(3)(i) of this section shall not apply to a... block of stock to preclude nonqualified shareholders in the closely-held block of stock from owning 50 percent or more of the total value of the class of stock of which the closely-held block is a part for...

26 CFR 1.883-2 - Treatment of publicly-traded corporations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... closely-held block of stock. (ii) Exception. Paragraph (d)(3)(i) of this section shall not apply to a... block of stock to preclude nonqualified shareholders in the closely-held block of stock from owning 50 percent or more of the total value of the class of stock of which the closely-held block is a part for...

26 CFR 1.883-2 - Treatment of publicly-traded corporations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... closely-held block of stock. (ii) Exception. Paragraph (d)(3)(i) of this section shall not apply to a... block of stock to preclude nonqualified shareholders in the closely-held block of stock from owning 50 percent or more of the total value of the class of stock of which the closely-held block is a part for...

26 CFR 1.883-2 - Treatment of publicly-traded corporations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... closely-held block of stock. (ii) Exception. Paragraph (d)(3)(i) of this section shall not apply to a... block of stock to preclude nonqualified shareholders in the closely-held block of stock from owning 50 percent or more of the total value of the class of stock of which the closely-held block is a part for...

26 CFR 1.883-2 - Treatment of publicly-traded corporations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... closely-held block of stock. (ii) Exception. Paragraph (d)(3)(i) of this section shall not apply to a... block of stock to preclude nonqualified shareholders in the closely-held block of stock from owning 50 percent or more of the total value of the class of stock of which the closely-held block is a part for...

76 FR 36533 - Transcontinental Gas Pipe Line Company, LLC; Notice of Request Under Blanket Authorization

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...-000, for authorization to abandon in place: (i) Approximately 8.45 mile, 12- inch pipeline extending from South Marsh Island Block 38 to South Marsh Island Block 23, (ii) approximately 0.455 mile, 12-inch pipeline extending from production platform B in South Marsh Island Block 33 to South Marsh Island Block 38...

The angiotensin II receptor type 1b is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cells.

PubMed

Pires, Paulo W; Ko, Eun-A; Pritchard, Harry A T; Rudokas, Michael; Yamasaki, Evan; Earley, Scott

2017-07-15

The angiotensin II receptor type 1b (AT 1 R b ) is the primary sensor of intraluminal pressure in cerebral arteries. Pressure or membrane-stretch induced stimulation of AT 1 R b activates the TRPM4 channel and results in inward transient cation currents that depolarize smooth muscle cells, leading to vasoconstriction. Activation of either AT 1 R a or AT 1 R b with angiotensin II stimulates TRPM4 currents in cerebral artery myocytes and vasoconstriction of cerebral arteries. The expression of AT 1 R b mRNA is ∼30-fold higher than AT 1 R a in whole cerebral arteries and ∼45-fold higher in isolated cerebral artery smooth muscle cells. Higher levels of expression are likely to account for the obligatory role of AT 1 R b for pressure-induced vasoconstriction . ABSTRACT: Myogenic vasoconstriction, which reflects the intrinsic ability of smooth muscle cells to contract in response to increases in intraluminal pressure, is critically important for the autoregulation of blood flow. In smooth muscle cells from cerebral arteries, increasing intraluminal pressure engages a signalling cascade that stimulates cation influx through transient receptor potential (TRP) melastatin 4 (TRPM4) channels to cause membrane depolarization and vasoconstriction. Substantial evidence indicates that the angiotensin II receptor type 1 (AT 1 R) is inherently mechanosensitive and initiates this signalling pathway. Rodents express two types of AT 1 R - AT 1 R a and AT 1 R b - and conflicting studies provide support for either isoform as the primary sensor of intraluminal pressure in peripheral arteries. We hypothesized that mechanical activation of AT 1 R a increases TRPM4 currents to induce myogenic constriction of cerebral arteries. However, we found that development of myogenic tone was greater in arteries from AT 1 R a knockout animals compared with controls. In patch-clamp experiments using native cerebral arterial myocytes, membrane stretch-induced cation currents were blocked by the TRPM4 inhibitor 9-phenanthrol in both groups. Further, the AT 1 R blocker losartan (1 μm) diminished myogenic tone and blocked stretch-induced cation currents in cerebral arteries from both groups. Activation of AT 1 R with angiotensin II (30 nm) also increased TRPM4 currents in smooth muscle cells and constricted cerebral arteries from both groups. Expression of AT 1 R b mRNA was ∼30-fold greater than AT 1 R a in cerebral arteries, and knockdown of AT 1 R b selectively diminished myogenic constriction. We conclude that AT 1 R b , acting upstream of TRPM4 channels, is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cells. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

PubMed

Tsunoo, A; Yoshii, M; Narahashi, T

1986-12-01

Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca2+ channel currents in neuroblastoma-glioma hybrid cells (NG108-15). The long-lasting (type 2) component of the Ca2+ channel current was blocked by leucine-enkephalin, while the transient (type 1) component was not affected. The enkephalin-induced blocking action was antagonized by naloxone and appears to be mediated by delta-opiate receptors. Two different aspects of the blocking effect were detected, a resting block and a recovery from block during prolonged depolarizing pulses. Recovery from block was more complete, and its time course was more rapid, with depolarization to more positive potentials. The dose dependence of the type 2 channel block at rest indicated a one-to-one binding stoichiometry, with an apparent dissociation constant of 8.8 nM. Somatostatin exerted a similar selective blocking action on the type 2 Ca2+ channel. The time- and voltage-dependent block of type 2 Ca2+ channels may provide a mechanism underlying the enkephalinergic presynaptic inhibition of transmitter release and the somatostatin block of pituitary growth hormone release.

Nano-structured polymer composites and process for preparing same

DOEpatents

Hillmyer, Marc; Chen, Liang

2013-04-16

A process for preparing a polymer composite that includes reacting (a) a multi-functional monomer and (b) a block copolymer comprising (i) a first block and (ii) a second block that includes a functional group capable of reacting with the multi-functional monomer, to form a crosslinked, nano-structured, bi-continuous composite. The composite includes a continuous matrix phase and a second continuous phase comprising the first block of the block copolymer.

Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.

PubMed Central

Dransfield, D T; Bradford, A J; Smith, J; Martin, M; Roy, C; Mangeat, P H; Goldenring, J R

1997-01-01

cAMP-dependent protein kinase (A-kinase) anchoring proteins (AKAPs) are responsible for the subcellular sequestration of the type II A-kinase. Previously, we identified a 78 kDa AKAP which was enriched in gastric parietal cells. We have now purified the 78 kDa AKAP to homogeneity from gastric fundic mucosal supernates using type II A-kinase regulatory subunit (RII) affinity chromatography. The purified 78 kDa AKAP was recognized by monoclonal antibodies against ezrin, the canalicular actin-associated protein. Recombinant ezrin produced in either Sf9 cells or bacteria also bound RII. Recombinant radixin and moesin, ezrin-related proteins, also bound RII in blot overlay. Analysis of recombinant truncations of ezrin mapped the RII binding site to a region between amino acids 373 and 439. This region contained a 14-amino-acid amphipathic alpha-helical putative RII binding region. A synthetic peptide containing the amphipathic helical region (ezrin409-438) blocked RII binding to ezrin, but a peptide with a leucine to proline substitution at amino acid 421 failed to inhibit RII binding. In mouse fundic mucosa, RII immunoreactivity redistributed from a predominantly cytosolic location in resting parietal cells, to a canalicular pattern in mucosa from animals stimulated with gastrin. These results demonstrate that ezrin is a major AKAP in gastric parietal cells and may function to tether type II A-kinase to a region near the secretory canaliculus. PMID:9009265

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

PubMed

Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U

2016-05-01

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®

Predictors of favorable soft tissue profile outcomes following Class II Twin-block treatment

PubMed Central

Kim, Ji-Eun; Mah, Su-Jung; Kim, Tae-Woo; Kim, Su-Jung; Park, Ki-Ho

2018-01-01

Objective The aim of this study was to determine cephalometric factors that help predict favorable soft-tissue profile outcomes following treatment with the Class II Twin-block appliance. Methods Pre- and post-treatment lateral cephalograms of 45 patients treated with the Class II Twin-block appliance were retrospectively analyzed. Profile silhouettes were drawn from the cephalograms and evaluated by three orthodontists in order to determine the extent of improvement. Samples were divided into a favorable group (upper 30% of visual analogue scale [VAS] scores, n = 14) and an unfavorable group (lower 30% of VAS scores, n = 14). Skeletal and soft-tissue measurements were performed on the cephalograms and an intergroup comparison was conducted. Results An independent t-test revealed that the following pre-treatment values were lower in the favorable group compared to the unfavorable group: lower incisor to mandibular plane angle, lower incisor to pogonion distance, point A-nasion-point B angle, sella-nasion line (SN) to maxillary plane angle, SN to mandibular plane angle, gonial angle, and symphysis inclination. The favorable group had a larger incisor inclination to occlusal plane. Moreover, the favorable group showed larger post-treatment changes in gonial angle, B point projection, and pogonion projection than did the unfavorable group. Conclusions Class II malocclusion patients with a low divergent skeletal pattern and reduced lower incisor protrusions are likely to show more improvement in soft-tissue profile outcomes following Class II Twin-block treatment. PMID:29291184

The anteroventral third ventricle region is critical for the behavioral desensitization caused by repeated injections of angiotensin II

PubMed Central

Vento, Peter J.; Daniels, Derek

2013-01-01

A single central injection of angiotensin II (AngII) potently increases water intake; however, a growing body of research suggests that repeated, acute intracerebroventricular injections of AngII cause a reduction in the dipsogenic response to subsequent AngII. This AngII-induced behavioral desensitization is specific to the effects of angiotensin and mediated by the angiotensin type-1 (AT1) receptor. The neuroanatomical substrate for this phenomenon, however, remains unknown. The anteroventral third ventricle region (AV3V) is an important site for the behavioral and physiological actions of AngII. Therefore, we hypothesized that this region also mediates the effects of repeated central AngII administration. In support of this hypothesis, we found that repeated injections of AngII into the AV3V reduced water intake stimulated by a test injection of AngII given into this region. Moreover, repeated AngII injections in the AV3V reduced water intake after AngII was injected into the lateral ventricle. These studies also demonstrate that activation of the AT1 receptor within the AV3V is required for AngII-induced behavioral desensitization because direct injection of the AT1 receptor antagonist, losartan, into the AV3V blocked the desensitizing effect of repeated AngII injections into the lateral ventricle. These findings provide additional support for a role of the AV3V in the dipsogenic actions of AngII, and suggest that this region is critical for the desensitization that occurs after acute repeated central injections of AngII. PMID:24144549

The effect of multicolored machinable ceramics on the esthetics of all-ceramic crowns.

PubMed

Reich, Sven; Hornberger, Helga

2002-07-01

Computer-aided design/computer-assisted machining systems offer the possibility of fabricating restorations from one machinable ceramic block. Whether multishaded blocks improve esthetic results and are a viable alternative to individually stained ceramics has not been fully determined. The aim of this investigation was to examine the effect of multishaded blocks on the esthetic appearance of all-ceramic CEREC crowns and compare these crowns with single-shade and stained restorations. Ten subjects were included in this study. For each subject, 6 different crowns were milled with the use of a CEREC machine. One crown was milled from each of the following machinable ceramic materials: CEREC Vitablocs Mark II in classic colors; Vitablocs Mark II in 3D-Master colors; Vitablocs Mark II in either classic or 3D-Master colors, with additional staining; Megadenta Bloxx multishaded; Mark II experimental multilayer; and an experimental multilayer leucite ceramic. Three independent examiners assessed the esthetic appearance of crowns fabricated to match each subject's anterior tooth shade. A scale of 1 to 6 was used to score the shade match and esthetic adaptation of each crown, with 1 representing excellent characteristics and 3.5 serving as the threshold for clinical acceptability. The examiners' scores were averaged, and the mean values were analyzed with the Wilcoxon signed rank test (P

Luminescent Photoelectrochemical Cells. 6. Spatial Aspects of the Photoluminescence and Electroluminescence of Cadmium Selenide Electrodes.

DTIC Science & Technology

1981-10-06

STRECKERT, J TONS, A B ELLIS N01478-C5633 UNCLASSI1FIED TRAS NL OFFICE OF NAVAL RESEARCH Contract No. N00014-78’-C-0633 Task No. NR 051-690 TECHNICAL REPORT...of Wisconsin NR 051-690 Madison, Wisconsin 53706 II. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE *Office of Naval Research /Chemistry Program...identify by block number) Samples of single-crystal, n-type CdSe emit when excited with ultraband gap excitation. The emission band (Xmax 񔊐 nm) is

Diverse mineral compositions, textures, and metamorphic P-T conditions of the glaucophane-bearing rocks in the Tamayen mélange, Yuli belt, eastern Taiwan

NASA Astrophysics Data System (ADS)

Tsai, Chin-Ho; Iizuka, Yoshiyuki; Ernst, W. G.

2013-02-01

This paper presents new petrologic data for high-pressure, low-temperature (HP-LT) metamorphic rocks at Juisui. We reinterpret the so-called "Tamayen block" (Yang and Wang, 1985) or "Juisui block" (Liou, 1981; Beyssac et al., 2008) as a tectonic mélange. It is not a coherent sheet but rather a mixture dominated by greenschist and pelitic schist with pods of serpentinite, epidote amphibolite, and rare blueschist. Four types of glaucophane-bearing rocks are newly recognized in this mélange. Type I is in contact with greenschist lacking glaucophane and garnet. Glaucophane is present only as rare inclusions within pargasite. This type records metamorphic evolution from epidote blueschists-, epidote amphibolite-, to greenschist-facies. Type II contains characteristic zoned amphiboles from barroisite core to Mg-katophorite mantle and glaucophane rim, implying an epidote amphibolite-facies stage overprinted by an epidote blueschists-facies one. Type III includes winchite and indicates P-T conditions of about 6-8 kbar, approaching 400 °C. Type IV contains paragonite but lacks garnet; amphibole shows a Na-Ca core surrounded by a glaucophane rim. This type shows a high-pressure (?) epidote amphibolite-facies stage overprinted by an epidote blueschists-facies one. Amphibole zoning trends and mineral assemblages imply contradictory P-T paths for the four types of glaucophane-bearing rocks—consistent with the nature of a tectonic mélange. The new P-T constraints and petrologic findings differ from previous studies (Liou et al., 1975; Beyssac et al., 2008).

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus.

PubMed

Tong, Jing; Lai, Yan; Yao, Yi-An; Wang, Xue-Jun; Shi, Yu-Shuang; Hou, Han-Jin; Gu, Jian-Yun; Chen, Fei; Liu, Xue-Bo

2018-06-19

To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice. © 2018 The Author(s). Published by S. Karger AG, Basel.

The effect of hyperkalaemia on cardiac rhythm devices.

PubMed

Barold, S Serge; Herweg, Bengt

2014-04-01

In patients with pacemakers, hyperkalaemia causes three important abnormalities that usually become manifest when the K level exceeds 7 mEq/L: (i) widening of the paced QRS complex from delayed intraventricular conduction velocity, (ii) Increased atrial and ventricular pacing thresholds that may cause failure to capture. In this respect, the atria are more susceptible to loss of capture than the ventricles, and (iii) Increased latency (usually with ventricular pacing) manifested by a greater delay of the interval from the pacemaker stimulus to the onset of depolarization. First-degree ventricular pacemaker exit block may progress to second-degree Wenckebach (type I) exit block characterized by gradual prolongation of the interval from the pacemaker stimulus to the onset of the paced QRS complex ultimately resulting in an ineffectual stimulus. The disturbance may then progress to 2 : 1, 3 : 1 pacemaker exit block, etc., and eventually to complete exit block with total lack of capture. Ventricular undersensing is uncommonly observed because of frequent antibradycardia pacing. During managed ventricular pacing, hyperkalaemia-induced marked first-degree atrioventricular block may induce a pacemaker syndrome. With implantable cardioverter-defibrillators (ICDs) oversensing of the paced or spontaneous T-wave may occur. The latter may cause inappropriate shocks. A raised impedance from the right ventricular coil to the superior vena cava coil may become an important sign of hyperkalaemia in the asymptomatic or the minimally symptomatic ICD patient.

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.

PubMed

Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; De Lerma Barbaro, Andrea; Casoli, Claudio; Accolla, Roberto S

2006-08-22

The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide–High Angiotensin II–Induced Cardiovascular Injury

PubMed Central

Pojoga, Luminita H.; Yao, Tham M.; Opsasnick, Lauren A.; Siddiqui, Waleed T.; Reslan, Ossama M.; Adler, Gail K.; Williams, Gordon H.

2015-01-01

Aldosterone interacts with mineralocorticoid receptor (MR) to stimulate sodium reabsorption in renal tubules and may also affect the vasculature. Caveolin-1 (cav-1), an anchoring protein in plasmalemmal caveolae, binds steroid receptors and also endothelial nitric oxide synthase, thus limiting its translocation and activation. To test for potential MR/cav-1 interaction in the vasculature, we investigated if MR blockade in cav-1–replete or –deficient states would alter vascular function in a mouse model of low nitric oxide (NO)–high angiotensin II (AngII)–induced cardiovascular injury. Wild-type (WT) and cav-1 knockout mice (cav-1−/−) consuming a high salt diet (4% NaCl) received Nω-nitro-l-arginine methyl ester (L-NAME) (0.1–0.2 mg/ml in drinking water at days 1–11) plus AngII (0.7–2.8 mg/kg per day via an osmotic minipump at days 8–11) ± MR antagonist eplerenone (EPL) 100 mg/kg per day in food. In both genotypes, blood pressure increased with L-NAME + AngII. EPL minimally changed blood pressure, although its dose was sufficient to block MR and reverse cardiac expression of the injury markers cluster of differentiation 68 and plasminogen activator inhibitor-1 in L-NAME+AngII treated mice. In aortic rings, phenylephrine and KCl contraction was enhanced with EPL in L-NAME+AngII treated WT mice, but not cav-1−/− mice. AngII-induced contraction was not different, and angiotensin type 1 receptor expression was reduced in L-NAME + AngII treated WT and cav-1−/− mice. In WT mice, acetylcholine-induced relaxation was enhanced with L-NAME + AngII treatment and reversed with EPL. Acetylcholine relaxation in cav-1−/− mice was greater than in WT mice, not modified by L-NAME + AngII or EPL, and blocked by ex vivo L-NAME, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or endothelium removal, suggesting the role of NO-cGMP. Cardiac endothelial NO synthase was increased in cav-1−/− versus WT mice, further increased with L-NAME + AngII, and not affected by EPL. Vascular relaxation to the NO donor sodium nitroprusside was increased with L-NAME + AngII in WT mice but not in cav-1−/− mice. Plasma aldosterone levels increased and cardiac MR expression decreased in L-NAME + AngII treated WT and cav-1−/− mice and did not change with EPL. Thus, during L-NAME + AngII induced hypertension, MR blockade increases contraction and alters vascular relaxation via NO-cGMP, and these changes are absent in cav-1 deficiency states. The data suggest a cooperative role of MR and cav-1 in regulating vascular contraction and NO-cGMP–mediated relaxation during low NO–high AngII–dependent cardiovascular injury. PMID:26183312

Comparing two quantitative methods for studying remineralization of artificial caries.

PubMed

Lo, E C M; Zhi, Q H; Itthagarun, A

2010-04-01

To compare the detection of changes before and after remineralization of artificial enamel and dentin caries by microCT scanning, polarized light microscopy (PLM) and transverse microradiography (TMR). Fourteen extracted premolars were cut into tooth blocks and painted with an acid-resistant varnish leaving one enamel and one dentin surface exposed. The tooth blocks were immersed into demineralizing solution for 4 days to produce artificial caries-like lesions and scanned by microCT. Then the 14 tooth blocks were randomly allocated into two groups. Seven tooth blocks in Group I were cut longitudinally through the exposed surface into 100-150 microm thick sections and microradiographs were taken. The other seven tooth blocks in Group II were left intact. All the tooth blocks and sections were then immersed into remineralizing solution for 5 days. PLM and TMR of the tooth sections in Group I were taken again. Depth of the lesion on the TMR was measured. Tooth blocks in Group II were scanned by microCT. Mean lesion depth in Group I reduced by 13.0% and 8.2% after remineralization for enamel and dentin, respectively (paired t-test, P<0.001). In Group II, linear attenuation coefficient (LAC) of the region of interest (ROI) increased by 11.1% and 23.8% after remineralization for enamel and dentin lesions, respectively (paired t-test, P<0.001). Both microCT and microradiography are able to detect a change of similar magnitude in the artificial caries lesions after remineralization. MicroCT may be used to substitute TMR and PLM in in vitro studies about caries. Copyright 2010 Elsevier Ltd. All rights reserved.

Postoperative analgesic efficiency of transversus abdominis plane block after ventral hernia repair: a prospective, randomized, controlled clinical trial.

PubMed

Chesov, Ion; Belîi, Adrian

2017-10-01

Effective postoperative analgesia is a key element in reducing postoperative morbidity, accelerating recovery and avoiding chronic postoperative pain. The aim of this study was to evaluate the effectiveness of ultrasound-guided Transversus Abdominis Plane (TAP) block, performed before surgical incision, in providing postoperative analgesia for patients undergoing open ventral hernia repair under general anaesthesia. Seventy elective patients scheduled for open ventral hernia repair surgery under general anaesthesia were divided randomly into two equal groups: Group I received bilateral TAP block performed before surgical incision (n = 35); Group II received systemic postoperative analgesia with parenteral opioid (morphine) alone (n = 35). Postoperatively pain scores at rest and with movement, total morphine consumption and opioid related side effects were recorded. Postoperative pain scores at rest and mobilization/cough were significantly higher in patients without TAP block (p < 0.05). Mean intraoperative fentanyl consumption was comparable between the two groups: 0.75 ± 0.31 mg in group I (TAP) and 0.86 ± 0.29 mg in group II (MO), p = 0.1299. Patients undergoing preincisional TAP block had reduced morphine requirements during the first 24 hours after surgery, compared to patients from group II, without TAP block (p = 0.0001). There was no difference in the incidence of opioid related side effects (nausea, vomiting) in the both groups during the first 24 postoperative hours. The use of preincisional ultrasound guided TAP block reduced the pain scores at rest and with movement/cough, opioid consumption and opioid-related side effects after ventral hernia repair when compared with opioid-only analgesia.

Clostridium botulinum C2 toxin. Identification of the binding site for chloroquine and related compounds and influence of the binding site on properties of the C2II channel.

PubMed

Neumeyer, Tobias; Schiffler, Bettina; Maier, Elke; Lang, Alexander E; Aktories, Klaus; Benz, Roland

2008-02-15

Clostridium botulinum C2 toxin belongs to the family of binary AB type toxins that are structurally organized into distinct enzyme (A, C2I) and binding (B, C2II) components. The proteolytically activated 60-kDa C2II binding component is essential for C2I transport into target cells. It oligomerizes into heptamers and forms channels in lipid bilayer membranes. The C2II channel is cation-selective and can be blocked by chloroquine and related compounds. Residues 303-330 of C2II contain a conserved pattern of alternating hydrophobic and hydrophilic residues, which has been implicated in the formation of two amphipathic beta-strands involved in membrane insertion and channel formation. In the present study, C2II mutants created by substitution of different negatively charged amino acids by alanine-scanning mutagenesis were analyzed in artificial lipid bilayer membranes. The results suggested that most of the C2II mutants formed SDS-resistant oligomers (heptamers) similar to wild type. The mutated negatively charged amino acids did not influence channel properties with the exception of Glu(399) and Asp(426), which are probably localized in the vestibule near the channel entrance. These mutants show a dramatic decrease in their affinity for binding of chloroquine and its analogues. Similarly, F428A, which represents the Phi-clamp in anthrax protective antigen, was mutated in C2II in several other amino acids. The C2II mutants F428A, F428D, F428Y, and F428W not only showed altered chloroquine binding but also had drastically changed single channel properties. The results suggest that amino acids Glu(399), Asp(426), and Phe(428) have a major impact on the function of C2II as a binding protein for C2I delivery into target cells.

Enhanced hemodynamic responses to angiotensin II in diabetes are associated with increased expression and activity of AT1 receptors in the afferent arteriole.

PubMed

Zhang, Jie; Qu, Helena Y; Song, Jiangping; Wei, Jin; Jiang, Shan; Wang, Lei; Wang, Liqing; Buggs, Jacentha; Liu, Ruisheng

2017-10-01

The prevalence of hypertension is about twofold higher in diabetic than in nondiabetic subjects. Hypertension aggravates the progression of diabetic complications, especially diabetic nephropathy. However, the mechanisms for the development of hypertension in diabetes have not been elucidated. We hypothesized that enhanced constrictive responsiveness of renal afferent arterioles (Af-Art) to angiotensin II (ANG II) mediated by ANG II type 1 (AT1) receptors contributes to the development of hypertension in diabetes. In response to an acute bolus intravenous injection of ANG II, alloxan-induced diabetic mice exhibited a higher mean arterial pressure (MAP) (119.1 ± 3.8 vs. 106.2 ± 3.5 mmHg) and a lower renal blood flow (0.25 ± 0.07 vs. 0.52 ± 0.14 ml/min) compared with nondiabetic mice. In response to chronic ANG II infusion, the MAP measured with telemetry increased by 55.8 ± 6.5 mmHg in diabetic mice, but only by 32.3 ± 3.8 mmHg in nondiabetic mice. The mRNA level of AT1 receptor increased by ~10-fold in isolated Af-Art of diabetic mice compared with nondiabetic mice, whereas ANG II type 2 (AT2) receptor expression did not change. The ANG II dose-response curve of the Af-Art was significantly enhanced in diabetic mice. Moreover, the AT1 receptor antagonist, losartan, blocked the ANG II-induced vasoconstriction in both diabetic mice and nondiabetic mice. In conclusion, we found enhanced expression of the AT1 receptor and exaggerated response to ANG II of the Af-Art in diabetes, which may contribute to the increased prevalence of hypertension in diabetes. Copyright © 2017 the American Physiological Society.

Association between Three Mutations, F1565C, V1023G and S996P, in the Voltage-Sensitive Sodium Channel Gene and Knockdown Resistance in Aedes aegypti from Yogyakarta, Indonesia

PubMed Central

Rochmijati Wuliandari, Juli; Lee, Siu Fai; White, Vanessa Linley; Tantowijoyo, Warsito; Hoffmann, Ary Anthony; Endersby-Harshman, Nancy Margaret

2015-01-01

Mutations in the voltage-sensitive sodium channel gene (Vssc) have been identified in Aedes aegypti and some have been associated with pyrethroid insecticide resistance. Whether these mutations cause resistance, alone or in combination with other alleles, remains unclear, but must be understood if mutations are to become markers for resistance monitoring. We describe High Resolution Melt (HRM) genotyping assays for assessing mutations found in Ae. aegypti in Indonesia (F1565C, V1023G, S996P) and use them to test for associations with pyrethroid resistance in mosquitoes from Yogyakarta, a city where insecticide use is widespread. Such knowledge is important because Yogyakarta is a target area for releases of Wolbachia-infected mosquitoes with virus-blocking traits for dengue suppression. We identify three alleles across Yogyakarta putatively linked to resistance in previous research. By comparing resistant and susceptible mosquitoes from bioassays, we show that the 1023G allele is associated with resistance to type I and type II pyrethroids. In contrast, F1565C homozygotes were rare and there was only a weak association between individuals heterozygous for the mutation and resistance to a type I pyrethroid. As the heterozygote is expected to be incompletely recessive, it is likely that this association was due to a different resistance mechanism being present. A resistance advantage conferred to V1023G homozygotes through addition of the S996P allele in the homozygous form was suggested for the Type II pyrethroid, deltamethrin. Screening of V1023G and S996P should assist resistance monitoring in Ae. aegypti from Yogyakarta, and these mutations should be maintained in Wolbachia strains destined for release in this city to ensure that these virus-blocking strains of mosquitoes are not disadvantaged, relative to resident populations. PMID:26463408

Association between Three Mutations, F1565C, V1023G and S996P, in the Voltage-Sensitive Sodium Channel Gene and Knockdown Resistance in Aedes aegypti from Yogyakarta, Indonesia.

PubMed

Wuliandari, Juli Rochmijati; Lee, Siu Fai; White, Vanessa Linley; Tantowijoyo, Warsito; Hoffmann, Ary Anthony; Endersby-Harshman, Nancy Margaret

2015-07-23

Mutations in the voltage-sensitive sodium channel gene (Vssc) have been identified in Aedes aegypti and some have been associated with pyrethroid insecticide resistance. Whether these mutations cause resistance, alone or in combination with other alleles, remains unclear, but must be understood if mutations are to become markers for resistance monitoring. We describe High Resolution Melt (HRM) genotyping assays for assessing mutations found in Ae. aegypti in Indonesia (F1565C, V1023G, S996P) and use them to test for associations with pyrethroid resistance in mosquitoes from Yogyakarta, a city where insecticide use is widespread. Such knowledge is important because Yogyakarta is a target area for releases of Wolbachia-infected mosquitoes with virus-blocking traits for dengue suppression. We identify three alleles across Yogyakarta putatively linked to resistance in previous research. By comparing resistant and susceptible mosquitoes from bioassays, we show that the 1023G allele is associated with resistance to type I and type II pyrethroids. In contrast, F1565C homozygotes were rare and there was only a weak association between individuals heterozygous for the mutation and resistance to a type I pyrethroid. As the heterozygote is expected to be incompletely recessive, it is likely that this association was due to a different resistance mechanism being present. A resistance advantage conferred to V1023G homozygotes through addition of the S996P allele in the homozygous form was suggested for the Type II pyrethroid, deltamethrin. Screening of V1023G and S996P should assist resistance monitoring in Ae. aegypti from Yogyakarta, and these mutations should be maintained in Wolbachia strains destined for release in this city to ensure that these virus-blocking strains of mosquitoes are not disadvantaged, relative to resident populations.

The PECS II block as a major analgesic component for clavicle operations: A description of 7 case reports.

PubMed

Schuitemaker R, J B; Sala-Blanch, X; Rodriguez-Pérez, C L; Mayoral R, J T; López-Pantaleon, L A; Sánchez-Cohen, A P

2018-01-01

Clavicle fractures correspond to 35% of traumatic fractures of the shoulder girdle. Regional anaesthesia has shown better analgesic results than systemic treatment for perioperative management. Innervation of the clavicle is complex, at present its knowledge raises controversy. The lateral pectoral nerve through the innervating musculature predominantly participates in the lateral and anterior part of the clavicle. The following report of 7 cases describes the effective postoperative analgesia of modified PEC II block in patients with middle third clavicle fracture or acromioclavicular dislocation who underwent a modified PEC II block for postoperative pain management, in the context of a multimodal analgesia. The potential advantage of this management over other analgesic procedures should be evaluated in specific clinical trials. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

The advanced receiver 2: Telemetry test results in CTA 21

NASA Technical Reports Server (NTRS)

Hinedi, S.; Bevan, R.; Marina, M.

1991-01-01

Telemetry tests with the Advanced Receiver II (ARX II) in Compatibility Test Area 21 are described. The ARX II was operated in parallel with a Block-III Receiver/baseband processor assembly combination (BLK-III/BPA) and a Block III Receiver/subcarrier demodulation assembly/symbol synchronization assembly combination (BLK-III/SDA/SSA). The telemetry simulator assembly provided the test signal for all three configurations, and the symbol signal to noise ratio as well as the symbol error rates were measured and compared. Furthermore, bit error rates were also measured by the system performance test computer for all three systems. Results indicate that the ARX-II telemetry performance is comparable and sometimes superior to the BLK-III/BPA and BLK-III/SDA/SSA combinations.

Metamorphic P-T path and zircon U-Pb dating of HP mafic granulites in the Yushugou granulite-peridotite complex, Chinese South Tianshan, NW China

NASA Astrophysics Data System (ADS)

Zhang, Lu; Zhang, Lifei; Xia, Bin; Lü, Zeng

2018-03-01

Co-existing granulite and peridotite may represent relics of the paleo-suture zone and provides an optimal opportunity for better understanding of orogeny between two blocks. In this study, we carried out petrological and U-Pb zircon dating investigation on the HP mafic granulites associated with peridotite complex at Yushugou in Chinese South Tianshan. The studied samples include garnet-bearing high-pressure mafic granulites which can be subdivided into two types: Type I orthopyroxene-free and Type II orthopyroxene-bearing granulites and amphibolite. Type I granulite (Y21-2) has a mineral assemblage of garnet (33 vol.%), clinopyroxene (32 vol.%) and plagioclase (30 vol.%); and Type II granulite (Y18-8) has a mineral assemblage of garnet (22 vol.%), clinopyroxene (10 vol.%), orthopyroxene (14 vol.%), plagioclase (45 vol.%) and quartz. Garnet in both granulites exhibits core-rim structure characterized by increasing grossular and decreasing pyrope from core to rim. Petrographic observations and phase equilibrium modeling using THERMOCALC in the NCFMASHTO system for the mafic granulites (Y21-2 and Y18-8) show three stages of metamorphism: Stage I (granulite facies) was recognized by the large porphyroblastic garnet core, with P-T conditions of 9.8-10.4 Kbar and 860-900 °C (Y21-2) and 9.9-10.6 Kbar and 875-890 °C (Y18-8), respectively; Stage II (HP granulite facies) has peak P-T conditions of 12.1 Kbar at 755 °C (Y21-2) and 13.8 Kbar at 815 °C (Y18-8) using mineral assemblages combining with garnet rim compositions with maximum grossular and minimum pyrope contents; Stage III (amphibolite facies) was characterized by the development of calcic amphibole in granulites with temperature of 446-563 °C. Therefore, an anticlockwise P-T path characterized by simultaneous temperature-decreasing and pressure-increasing was inferred for the Yushugou HP mafic granulite. Studies of zircon morphology and inclusions, combined with zircon U-Pb dating and REE geochemistry indicate that their protolith's ages of the mafic granulites were ∼430 Ma, while the metamorphism could occur at three stages with ages of ∼390 Ma, ∼340 Ma and ∼320 Ma, which may correspond to Stage I, II and III, respectively. We interpret the HP mafic granulites from the Yushugou granulite-peridotite complex to be formed by the cooling subduction of the lower crustal rocks from the hanging wall of central Tianshan block during the northward subduction of the south Tianshan paleo-ocean from Devonian to Carboniferous.

Opioid receptors regulate blocking and overexpectation of fear learning in conditioned suppression.

PubMed

Arico, Carolyn; McNally, Gavan P

2014-04-01

Endogenous opioids play an important role in prediction error during fear learning. However, the evidence for this role has been obtained almost exclusively using the species-specific defense response of freezing as the measure of learned fear. It is unknown whether opioid receptors regulate predictive fear learning when other measures of learned fear are used. Here, we used conditioned suppression as the measure of learned fear to assess the role of opioid receptors in fear learning. Experiment 1a studied associative blocking of fear learning. Rats in an experimental group received conditioned stimulus A (CSA) + training in Stage I and conditioned stimulus A and B (CSAB) + training in Stage II, whereas rats in a control group received only CSAB + training in Stage II. The prior fear conditioning of CSA blocked fear learning to conditioned stimulus B (CSB) in the experimental group. In Experiment 1b, naloxone (4 mg/kg) administered before Stage II prevented this blocking, thereby enabling normal fear learning to CSB. Experiment 2a studied overexpectation of fear. Rats received CSA + training and CSB + training in Stage I, and then rats in the experimental group received CSAB + training in Stage II whereas control rats did not. The Stage II compound training of CSAB reduced fear to CSA and CSB on test. In Experiment 2b, naloxone (4 mg/kg) administered before Stage II prevented this overexpectation. These results show that opioid receptors regulate Pavlovian fear learning, augmenting learning in response to positive prediction error and impairing learning in response to negative prediction error, when fear is assessed via conditioned suppression. These effects are identical to those observed when freezing is used as the measure of learned fear. These findings show that the role for opioid receptors in regulating fear learning extends across multiple measures of learned fear.

Spinal conduction block by intrathecal ketamine in dogs.

PubMed

Iida, H; Dohi, S; Tanahashi, T; Watanabe, Y; Takenaka, M

1997-07-01

In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Eric; Hamel, Rodolphe; Neyret, Aymeric

Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virusmore » and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. - Highlights: • Human keratinocytes support endocytosis of CHIKV and fusion of viral membranes. • CHIKV replication is blocked at a post entry step in these cells. • Infection upregulates type-I, –II and –III IFN genes expression. • Keratinocytes behave as immune sentinels against CHIKV.« less

Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy.

PubMed

Radtke, A; Sotiropoulos, G C; Molmenti, E P; Sgourakis, G; Schroeder, T; Beckebaum, S; Peitgen, H-O; Cicinnati, V R; Broelsch, C E; Broering, D C; Malagó, M

2012-03-01

The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor-individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates. © copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

In-hospital outcome in patients with ST elevation myocardial infarction and right bundle branch block. A sub-study from RENASICA II, a national multicenter registry.

PubMed

Juárez-Herrera, Ursulo; Jerjes Sánchez, Carlos; González-Pacheco, Héctor; Martínez-Sánchez, Carlos

2010-01-01

Compare in-hospital outcome in patients with ST-elevation myocardial infarction with right versus left bundle branch block. RENASICA II, a national Mexican registry enrolled 8098 patients with final diagnosis of acute coronary syndrome secondary to ischemic heart disease. In 4555 STEMI patients, 545 had bundle branch block, 318 (58.3%) with right and 225 patients with left (41.6%). Both groups were compared in terms of in-hospital outcome through major cardiovascular adverse events; (cardiovascular death, recurrent ischemia and reinfarction). Multivariable analysis was performed to identify in-hospital mortality risk among right and left bundle branch block patients. There were not statistical differences in both groups regarding baseline characteristics, time of ischemia, myocardial infarction location, ventricular dysfunction and reperfusion strategies. In-hospital outcome in bundle branch block group was characterized by a high incidence of major cardiovascular adverse events with a trend to higher mortality in patients with right bundle branch block (OR 1.70, CI 1.19 - 2.42, p < 0.003), compared to left bundle branch block patients. In this sub-study right bundle branch block accompanying ST-elevation myocardial infarction of any location at emergency room presentation was an independent predictor of high in-hospital mortality.

Mitogen-activated protein kinase is required for the behavioral desensitization that occurs after repeated injections of angiotensin II

PubMed Central

Vento, Peter J.; Daniels, Derek

2013-01-01

Angiotensin II (AngII) acts on central angiotensin type 1 (AT1) receptors to increase water and saline intake. Prolonged exposure to AngII in cell culture models results in a desensitization of the AT1 receptor that is thought to involve receptor internalization, and a behavioral correlate of this desensitization has been shown in rats after repeated central injections of AngII. Specifically, rats given repeated injections of AngII drink less water than controls after a subsequent test injection of AngII. Under the same conditions, however, repeated injections of AngII have no effect on AngII-induced saline intake. Given earlier studies indicating that separate intracellular signaling pathways mediate AngII-induced water and saline intake, we hypothesized that the desensitization observed in rats may be incomplete, leaving the receptor able to activate mitogen-activated protein (MAP) kinases (ERK1/2), which play a role in AngII-induced saline intake without affecting water intake. In support of this hypothesis, we found no difference in MAP kinase phosphorylation after an AngII test injection in rats given prior treatment with repeated injections of vehicle, AngII, or Sar1,Ile4,Ile8-AngII (SII), an AngII analog that activates MAP kinase without G protein coupling. In addition, we found that pretreatment with the MAP kinase inhibitor U0126 completely blocked the desensitizing effect of repeated AngII injections on water intake. Furthermore, AngII-induced water intake was reduced similarly by repeated injections of AngII or SII. The results suggest that G protein-independent signaling is sufficient to produce behavioral desensitization of the angiotensin system and that the desensitization requires MAP kinase activation. PMID:22581747

Mitogen-activated protein kinase is required for the behavioural desensitization that occurs after repeated injections of angiotensin II.

PubMed

Vento, Peter J; Daniels, Derek

2012-12-01

Angiotensin II (Ang II) acts on central angiotensin type 1 (AT(1)) receptors to increase water and saline intake. Prolonged exposure to Ang II in cell culture models results in a desensitization of the AT(1) receptor that is thought to involve receptor internalization, and a behavioural correlate of this desensitization has been shown in rats after repeated central injections of Ang II. Specifically, rats given repeated injections of Ang II drink less water than control animals after a subsequent test injection of Ang II. In the same conditions, however, repeated injections of Ang II have no effect on Ang II-induced saline intake. Given earlier studies indicating that separate intracellular signalling pathways mediate Ang II-induced water and saline intake, we hypothesized that the desensitization observed in rats may be incomplete, leaving the receptor able to activate mitogen-activated protein (MAP) kinases (ERK1/2), which play a role in Ang II-induced saline intake without affecting water intake. In support of this hypothesis, we found no difference in MAP kinase phosphorylation after an Ang II test injection in rats given prior treatment with repeated injections of vehicle, Ang II or Sar(1),Ile(4),Ile(8)-Ang II (SII), an Ang II analogue that activates MAP kinase without G protein coupling. In addition, we found that pretreatment with the MAP kinase inhibitor U0126 completely blocked the desensitizing effect of repeated Ang II injections on water intake. Furthermore, Ang II-induced water intake was reduced to a similar extent by repeated injections of Ang II or SII. The results suggest that G protein-independent signalling is sufficient to produce behavioural desensitization of the angiotensin system and that the desensitization requires MAP kinase activation.

Icariin attenuates angiotensin II-induced hypertrophy and apoptosis in H9c2 cardiomyocytes by inhibiting reactive oxygen species-dependent JNK and p38 pathways

PubMed Central

ZHOU, HENG; YUAN, YUAN; LIU, YUAN; DENG, WEI; ZONG, JING; BIAN, ZHOU-YAN; DAI, JIA; TANG, QI-ZHU

2014-01-01

Icariin, the major active component isolated from plants of the Epimedium family, has been reported to have potential protective effects on the cardiovascular system. However, it is not known whether icariin has a direct effect on angiotensin II (Ang II)-induced cardiomyocyte enlargement and apoptosis. In the present study, embryonic rat heart-derived H9c2 cells were stimulated by Ang II, with or without icariin administration. Icariin treatment was found to attenuate the Ang II-induced increase in mRNA expression levels of hypertrophic markers, including atrial natriuretic peptide and B-type natriuretic peptide, in a concentration-dependent manner. The cell surface area of Ang II-treated H9c2 cells also decreased with icariin administration. Furthermore, icariin repressed Ang II-induced cell apoptosis and protein expression levels of Bax and cleaved-caspase 3, while the expression of Bcl-2 was increased by icariin. In addition, 2′,7′-dichlorofluorescein diacetate incubation revealed that icariin inhibited the production of intracellular reactive oxygen species (ROS), which were stimulated by Ang II. Phosphorylation of c-Jun N-terminal kinase (JNK) and p38 in Ang II-treated H9c2 cells was blocked by icariin. Therefore, the results of the present study indicated that icariin protected H9c2 cardiomyocytes from Ang II-induced hypertrophy and apoptosis by inhibiting the ROS-dependent JNK and p38 pathways. PMID:24940396

Angiotensin II inhibits ADH-stimulated cAMP: role on O2- and transport-related oxygen consumption in the loop of Henle.

PubMed

Silva, G B; Juncos, L I; Baigorria, S T; Garcia, N H

2013-01-01

Dehydration and acute reductions of blood pressure increases ADH and Ang II levels. These hormones increase transport along the distal nephron. In the thick ascending limb (TAL) ADH increases transport via cAMP, while Ang II acts via superoxide (O2-). However, the mechanism of interaction of these hormones in this segment remains unclear. The aim of this study was to explore ADH/Ang II interactions on TAL transport. For this, we measured the effects of ADH/Ang II, added sequentially to TAL suspensions from Wistar rats, on oxygen consumption (QO2) -as a transport index-, cAMP and O2-. Basal QO2 was 112+-5 nmol O2/min/mg protein. Addition of ADH (1nM) increased QO2 by 227 percent. In the presence of ADH, Ang II (1nM) elicited a QO2 transient response. During an initial 3.1+-0.7 minutes after adding Ang II, QO2 decreased 58 percent (p less than 0.03 initial vs. ADH) and then rose by 188 percent (p less than 0.03 late vs initial Ang II). We found that Losartan blocked the initial effects of Ang II and the latter blocked ADH and forskolin-stimulated cAMP. The NOS inhibitor L-NAME or the AT2 receptor antagonist PD123319 showed no effect on transported related oxygen consumption. Then, we assessed the late period after adding Ang II. The O2- scavenger tempol blocked the late Ang II effects on QO2, while Ang II increased O2- production during this period. We conclude that 1) Ang II has a transient effect on ADH-stimulated transport; 2) this effect is mediated by AT1 receptors; 3) the initial period is mediated by decreased cAMP and 4) the late period is mediated by O2-.

Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies: unique epitopes may contribute to the regulation of thyroid function by the antibodies.

PubMed

Akamizu, T; Kohn, L D; Hiratani, H; Saijo, M; Tahara, K; Nakao, K

2000-06-01

Blocking-type TSH-binding inhibitor Igs (TBIIs) are known to cause hypothyroidism and an atrophic thyroid gland in patients with primary myxedema. They can block the activity of thyroid-stimulating antibodies (TSAbs) in Graves' patients as well as the activity of TSH. The majority of the epitopes for these blocking-type TBIIs have been, and are shown herein, to be present on the C-terminal region of the extracellular domain of the human TSH receptor (TSHR), whereas those for Graves' TSAbs are on the N-terminus. We report on a patient with Hashimoto's thyroiditis who suffered from mild hypothyroidism and a moderately sized goiter. Her serum had a potent blocking-type TBII and a weak TSAb in human and porcine TSHR systems. Using human TSHR/lutropin-CG receptor chimeras, we determined that the functional epitope of her blocking-type TBII was uniquely present on the N-terminal, rather than the C-terminal, region of the extracellular domain of the TSHR, unlike the case for blocking-type TBIIs in primary myxedema patients. The epitope of her TSAb was also unusual. Although the functional epitopes of most TSAbs are known to involve the N-terminal region of the receptor, her TSAb epitope did not seem to be present solely on the N- or C-terminus of the extracellular domain of the receptor. Blocking-type TBIIs from patients with primary myxedema blocked her TSAb activity as well as stimulation by TSH; her blocking-type TBII was able to only partially block her TSAb. In contrast, her blocking-type TBII almost completely blocked TSAbs from Graves' patients. Thus, we suggest that the unique epitopes of this patient's heterogeneous population of TSH receptor antibodies, at least in part, contribute to regulation of her thyroid function.

Study of the post-derailment safety measures on low-speed derailment tests

NASA Astrophysics Data System (ADS)

Guo, Lirong; Wang, Kaiyun; Lin, Jianhui; Zhang, Bing; Chen, Zaigang; Song, Xinwu; Du, Gaofeng

2016-07-01

Prevention of train from derailment is the most important issue for the railway system. Keeping derailed vehicle close to the track centreline is beneficial to minimise the severe consequences associated with derailments. In this paper, the post-derailment safety measures are studied based on low-speed derailment tests. Post-derailment devices can prevent deviation of the train from the rail by catching the rail, and they are mounted under the axle box. Considering the different structures of vehicles, both trailer and motor vehicles are equipped with the safety device and then separately used in low-speed derailment tests. In derailment tests, two kinds of track, namely the CRTS-I slab ballastless track and the CRTS-II bi-block sleeper ballastless track, are adopted to investigate the effect of the track types on the derailment. In addition, the derailment speed and the weight of the derailed vehicle are also taken into account in derailment tests. The test results indicate that the post-derailment movement of the vehicle includes running and bounce. Reducing the derailment speed and increasing the weight of the head of the train are helpful to reduce the possibility for derailments. For the CRTS-I slab ballastless track, the safety device can prevent trailer vehicles from deviating from the track centreline. The gearbox plays an important role in controlling the lateral displacement of motor vehicle after a derailment while the safety device contributes less to keep derailed motor vehicles on the track centreline. The lateral distance between the safety device and rails should be larger than 181.5 mm for protecting the fasteners system. And for the CRTS-II bi-block sleeper ballastless track, it helps to decrease the post-derailment distance due to the longitudinal impacts with sleepers. It can also restrict the lateral movement of derailed vehicle due to the high shoulders. The results suggest that, CRTS-II bi-block sleeper ballastless track should be widely used in derailment prone areas.

Integration of an Apple II Plus Computer into an Existing Dual Axis Sun Tracker System.

DTIC Science & Technology

1984-06-01

Identify by block number) S, tpec l Sun Tracker System Solar Energy Apple II Plus Computer 20. ABSTRACT (’ ntlnue on reveree ide If neceesery end...14 4. Dual Axis Sun Tracker (Side View) ----------------- 15 5. Solar Tracker System Block Diagram ---------------- 17 6. Plug Wiring Diagram for Top...sources will be competitive. Already many homes have solar collectors and other devices designed to decrease the consumption of gas, oil, and

Opioid receptors mediate direct predictive fear learning: evidence from one-trial blocking.

PubMed

Cole, Sindy; McNally, Gavan P

2007-04-01

Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including mu-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear learning. Four experiments reported here used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct or indirect action of predictive error on Pavlovian association formation. In Stage I, rats were trained to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were co-presented once and co-terminated with shock. Two novel stimuli, CSC and CSD, were also co-presented once and co-terminated with shock in Stage II. The results showed one-trial blocking of fear learning (Experiment 1) as well as one-trial unblocking of fear learning when Stage II training employed a higher intensity footshock than was used in Stage I (Experiment 2). Systemic administrations of the opioid receptor antagonist naloxone (Experiment 3) or intra-vlPAG administrations of the selective mu-opioid receptor antagonist CTAP (Experiment 4) prior to Stage II training prevented one-trial blocking. These results show that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation.

[Interface bond and compatibility between Mark II machining ceramic and vita VM9 veneering porcelain].

PubMed

Liu, Tian-Shuang; Li, Zhen-Chun; Chen, Xiao-Dong

2009-04-01

To investigate the interface bond and thermal compatibility between Mark II machining ceramic and Vita VM9 veneering porcelain. A bar shaped specimen (30 mm x 15 mm x 1 mm in size) of Mark II block was prepared, with 0.5 mm-deep notch (vertical to the long axis of specimen) at the middle of the bottom surface. The upper surface was veneered with 0.3 mm VM9 dentin base porcelain. Then the specimen was fractured from the notching site and the fracture surface was examined under scanning electron microscope (SEM) and electron microprobe analyzer (EMPA) with electron beam of 1 microm in diameter. Another ten specimens (30 mm x 15 mm x 1.5 mm in size) were fabricated and the temperature of thermal shock resistance were tested. SEM observation showed tight bond between these two materials and EMPA results showed penetration of Al element from Mark II block into veneering porcelain and Ca element from veneering porcelain into Mark II block occurred after sintering baking. The average temperature of thermal shock resistance for specimens in this study was (194.0+/-10.3) degrees C. Cracks were mainly distributed in veneering porcelain. Chemical bond exists between the Mark II machining ceramic and Vita VM9 veneering porcelain, and there is good thermal compatibility between them.

Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

PubMed

Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

2017-08-01

Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The anteroventral third ventricle region is critical for the behavioral desensitization caused by repeated injections of angiotensin II.

PubMed

Vento, Peter J; Daniels, Derek

2014-01-01

A single central injection of angiotensin II (AngII) potently increases water intake; however, a growing body of research suggests that repeated, acute intracerebroventricular injections of AngII cause a reduction in the dipsogenic response to subsequent AngII. This AngII-induced behavioral desensitization is specific to the effects of angiotensin and mediated by the angiotensin type-1 (AT1) receptor. The neuroanatomical substrate for this phenomenon, however, remains unknown. The anteroventral third ventricle (AV3V) region is an important site for the behavioral and physiological actions of AngII. Therefore, we hypothesized that this region also mediates the effects of repeated central AngII administration. In support of this hypothesis, we found that repeated injections of AngII into the AV3V reduced water intake stimulated by a test injection of AngII given into this region. Moreover, repeated AngII injections in the AV3V reduced water intake after AngII was injected into the lateral ventricle. These studies also demonstrate that activation of the AT1 receptor within the AV3V is required for AngII-induced behavioral desensitization because direct injection of the AT1 receptor antagonist, losartan, into the AV3V blocked the desensitizing effect of repeated AngII injections into the lateral ventricle. These findings provide additional support for a role of the AV3V in the dipsogenic actions of AngII, and suggest that this region is critical for the desensitization that occurs after acute repeated central injections of AngII. Copyright © 2013 Elsevier B.V. All rights reserved.

Electronic Principles II, 7-6. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This second of 10 blocks of student and teacher materials for a secondary/postsecondary level course in electronic principles comprises one of a number of military-developed curriculum packages selected for adaptation to vocational instruction and curriculum development in a civilian setting. A prerequisite is the previous block. This block on AC…

Fire Protection Specialist, Blocks I, II, & III, 17-2. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This military-developed text contains the first three blocks of a five-block course for use in training fire protection specialists. Covered in the individual volumes are the following topics: fire protection objectives and responsibilities (fire protection and occupational safety, extinguishing agents, principles and theory of combustion, natural…

Pharmacogenetic excitation of dorsomedial prefrontal cortex restores fear prediction error.

PubMed

Yau, Joanna Oi-Yue; McNally, Gavan P

2015-01-07

Pavlovian conditioning involves encoding the predictive relationship between a conditioned stimulus (CS) and an unconditioned stimulus, so that synaptic plasticity and learning is instructed by prediction error. Here we used pharmacogenetic techniques to show a causal relation between activity of rat dorsomedial prefrontal cortex (dmPFC) neurons and fear prediction error. We expressed the excitatory hM3Dq designer receptor exclusively activated by a designer drug (DREADD) in dmPFC and isolated actions of prediction error by using an associative blocking design. Rats were trained to fear the visual CS (CSA) in stage I via pairings with footshock. Then in stage II, rats received compound presentations of visual CSA and auditory CS (CSB) with footshock. This prior fear conditioning of CSA reduced the prediction error during stage II to block fear learning to CSB. The group of rats that received AAV-hSYN-eYFP vector that was treated with clozapine-N-oxide (CNO; 3 mg/kg, i.p.) before stage II showed blocking when tested in the absence of CNO the next day. In contrast, the groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIα-hM3Dq that were treated with CNO before stage II training did not show blocking; learning toward CSB was restored. This restoration of prediction error and fear learning was specific to the injection of CNO because groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIα-hM3Dq that were injected with vehicle before stage II training did show blocking. These effects were not attributable to the DREADD manipulation enhancing learning or arousal, increasing fear memory strength or asymptotic levels of fear learning, or altering fear memory retrieval. Together, these results identify a causal role for dmPFC in a signature of adaptive behavior: using the past to predict future danger and learning from errors in these predictions. Copyright © 2015 the authors 0270-6474/15/350074-10$15.00/0.

Angiotensin II stimulates basolateral 50-pS K channels in the thick ascending limb.

PubMed

Wang, Mingxiao; Luan, Haiyan; Wu, Peng; Fan, Lili; Wang, Lijun; Duan, Xinpeng; Zhang, Dandan; Wang, Wen-Hui; Gu, Ruimin

2014-03-01

We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.

Periodic nanostructures from self assembled wedge-type block-copolymers

DOEpatents

Xia, Yan; Sveinbjornsson, Benjamin R.; Grubbs, Robert H.; Weitekamp, Raymond; Miyake, Garret M.; Piunova, Victoria; Daeffler, Christopher Scot

2015-06-02

The invention provides a class of wedge-type block copolymers having a plurality of chemically different blocks, at least a portion of which incorporates a wedge group-containing block providing useful properties. For example, use of one or more wedge group-containing blocks in some block copolymers of the invention significantly inhibits chain entanglement and, thus, the present block copolymers materials provide a class of polymer materials capable of efficient molecular self-assembly to generate a range of structures, such as periodic nanostructures and microstructures. Materials of the present invention include copolymers having one or more wedge group-containing blocks, and optionally for some applications copolymers also incorporating one or more polymer side group-containing blocks. The present invention also provides useful methods of making and using wedge-type block copolymers.

The similar effects of verbal and non-verbal intervening tasks on word recall in an elderly population.

PubMed

Williams, B R; Sullivan, S K; Morra, L F; Williams, J R; Donovick, P J

2014-01-01

Vulnerability to retroactive interference has been shown to increase with cognitive aging. Consistent with the findings of memory and aging literature, the authors of the California Verbal Learning Test-II (CVLT-II) suggest that a non-verbal task be administered during the test's delay interval to minimize the effects of retroactive interference on delayed recall. The goal of the present study was to determine the extent to which retroactive interference caused by non-verbal and verbal intervening tasks affects recall of verbal information in non-demented, older adults. The effects of retroactive interference on recall of words during Long-Delay recall on the California Verbal Learning Test-II (CVLT-II) were evaluated. Participants included 85 adults age 60 and older. During a 20-minute delay interval on the CVLT-II, participants received either a verbal (WAIS-III Vocabulary or Peabody Picture Vocabulary Test-IIIB) or non-verbal (Raven's Standard Progressive Matrices or WAIS-III Block Design) intervening task. Similarly to previous research with young adults (Williams & Donovick, 2008), older adults recalled the same number of words across all groups, regardless of the type of intervening task. These findings suggest that the administration of verbal intervening tasks during the CVLT-II do not elicit more retroactive interference than non-verbal intervening tasks, and thus verbal tasks need not be avoided during the delay interval of the CVLT-II.

Internal electron transfer between hemes and Cu(II) bound at cysteine beta93 promotes methemoglobin reduction by carbon monoxide.

PubMed

Bonaventura, C; Godette, G; Tesh, S; Holm, D E; Bonaventura, J; Crumbliss, A L; Pearce, L L; Peterson, J

1999-02-26

Previous studies showed that CO/H2O oxidation provides electrons to drive the reduction of oxidized hemoglobin (metHb). We report here that Cu(II) addition accelerates the rate of metHb beta chain reduction by CO by a factor of about 1000. A mechanism whereby electron transfer occurs via an internal pathway coupling CO/H2O oxidation to Fe(III) and Cu(II) reduction is suggested by the observation that the copper-induced rate enhancement is inhibited by blocking Cys-beta93 with N-ethylmaleimide. Furthermore, this internal electron-transfer pathway is more readily established at low Cu(II) concentrations in Hb Deer Lodge (beta2His --> Arg) and other species lacking His-beta2 than in Hb A0. This difference is consistent with preferential binding of Cu(II) in Hb A0 to a high affinity site involving His-beta2, which is ineffective in promoting electron exchange between Cu(II) and the beta heme iron. Effective electron transfer is thus affected by Hb type but is not governed by the R left arrow over right arrow T conformational equilibrium. The beta hemes in Cu(II)-metHb are reduced under CO at rates close to those observed for cytochrome c oxidase, where heme and copper are present together in the oxygen-binding site and where internal electron transfer also occurs.

Effect of ractopamine-hydrochloride and trenbolone acetate on longissimus muscle fiber area, diameter, and satellite cell numbers in cull beef cows.

PubMed

Gonzalez, J M; Carter, J N; Johnson, D D; Ouellette, S E; Johnson, S E

2007-08-01

The objective of this study was to evaluate the effects of coadministration of ractopamine-HCl (RAC) and trenbolone acetate plus estradiol (TBA) on LM fiber cross-sectional area (CSA), diameter, fiber-associated myonuclei, and satellite cell number. Culled crossbred beef cows (n = 98; 11 +/- 1.8 yr old; BCS 4.3 +/- 0.03) from a single ranch in south Florida were fed a concentrate diet for 92 d in a 2 x 2, randomized block design. Cows were blocked by BW on arrival into light (initial BW = 369.75 +/- 2.68 kg and end BW = 501.96 +/- 6.90 kg) and heavy (initial BW = 418.31 +/- 2.75 kg and end BW = 522.15 +/- 7.09 kg) groups before assignment to treatment. Factors included dietary treatment (0 or 15 ppm) and implant status (0 or 80 mg of trenbolone acetate + 16 mg of estradiol). Ractopamine was provided in the diet to 2 pens or half the treatments during the final 35 d of feeding. Cows were slaughtered on d 92. Forty-eight hours postmortem, the 6th-rib portions of the LM were obtained from 10 randomly selected carcasses from each treatment group (n = 40). Cryosections (12 mum) were immunostained for dystrophin and myosin heavy chain I or II for the measurement of fiber CSA and type, respectively. Fiber-associated nuclei and satellite cell numbers were measured in serial cryosections. There was a RAC x TBA interaction (P < 0.05). Type I fiber CSA and diameter were increased (P < 0.05) by TBA and RAC. Type I CSA and diameter were larger (P < 0.05) in TBA + RAC than RAC only. Type II fiber CSA and diameter were not affected by TBA (P = 0.48), RAC (P = 0.15), or TBA + RAC (P = 0.60). Satellite cell numbers and fiber-associated nuclei were not affected (P > 0.05) by implant status or ractopamine supplementation. These results indicate that TBA and RAC preferentially increase the size of type I fibers in cull cows.

A novel mechanism by which hepatocyte growth factor blocks tubular epithelial to mesenchymal transition.

PubMed

Yang, Junwei; Dai, Chunsun; Liu, Youhua

2005-01-01

Hepatocyte growth factor (HGF) is a potent antifibrotic cytokine that blocks tubular epithelial to mesenchymal transition (EMT) induced by TGF-beta1. However, the underlying mechanism remains largely unknown. This study investigated the signaling events that lead to HGF blockade of the TGF-beta1-initiated EMT. Incubation of human kidney epithelial cells HKC with HGF only marginally affected the expression of TGF-beta1 and its type I and type II receptors, suggesting that disruption of TGF-beta1 signaling likely plays a critical role in mediating HGF inhibition of TGF-beta1 action. However, HGF neither affected TGF-beta1-induced Smad-2 phosphorylation and its subsequent nuclear translocation nor influenced the expression of inhibitory Smad-6 and -7 in tubular epithelial cells. HGF specifically induced the expression of Smad transcriptional co-repressor SnoN but not Ski and TG-interacting factor at both mRNA and protein levels in HKC cells. SnoN physically interacted with activated Smad-2 by forming transcriptionally inactive complex and overrode the profibrotic action of TGF-beta1. In vivo, HGF did not affect Smad-2 activation and its nuclear accumulation in tubular epithelium, but it restored SnoN protein abundance in the fibrotic kidney in obstructive nephropathy. Hence, HGF blocks EMT by antagonizing TGF-beta1's action via upregulating Smad transcriptional co-repressor SnoN expression. These findings not only identify a novel mode of interaction between the signals activated by HGF receptor tyrosine kinase and TGF-beta receptor serine/threonine kinases but also illustrate the feasibility of confining Smad activity as an effective strategy for blocking renal fibrosis.

Convergence to Diagonal Form of Block Jacobi-type Processes

NASA Astrophysics Data System (ADS)

Hari, Vjeran

2008-09-01

The main result of recent research on convergence to diagonal form of block Jacobi-type processes is presented. For this purpose, all notions needed to describe the result are introduced. In particular, elementary block transformation matrices, simple and non-simple algorithms, block pivot strategies together with the appropriate equivalence relations are defined. The general block Jacobi-type process considered here can be specialized to take the form of almost any known Jacobi-type method for solving the ordinary or the generalized matrix eigenvalue and singular value problems. The assumptions used in the result are satisfied by many concrete methods.

Testing block subdivision algorithms on block designs

NASA Astrophysics Data System (ADS)

Wiseman, Natalie; Patterson, Zachary

2016-01-01

Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

[Comparison of the activity and yield rate of osteoblast obtained by different digestion methods].

PubMed

Li, Ling-hui; Ding, Dao-Fang; Du, Guo-Qing; Wang, Hui-Hao; Zhan, Hong-Sheng

2013-04-01

To compared the activity and yield rate of osteoblast obtained by different collagenase digestion methods, to find a better way to extract osteoblast for the experimental researches of osteoporosis. Ten 24-hour-old SD rats were were euthanized. The cranium of rats were removed and cuted into blocks of 1 mm x 1 mm size. After digested by trypsin for 15 min, all the cranium were divided into two equal parts, and randomly divided into two groups which would be digested by type I collagenase and type II collagenase separately for two times. The rat cells of the two groups were cultured in thermostat incubator with 5% CO2 under the condition of 37 degrees C. The primary culture osteoblasts were counted by using a haemacytometer after digestion and 72 hours later. The second generation osteoblasts cultured 48 h were dyed by NBT/BCIP staining solution, and were detected by quantitative measurement with PNPP. The cells had irregular shapes. The results of cell counting showed that the cell number of type I group was larger than type 11 group. Alkaline phosphatase dyeing were positive. Detecting of alkaline phosphatase using the method of PNPP showed that the absorbance value in type I group were higher than type II group (P<0.05). Two types of collagenase are both suitable for the in vitro culture of rat osteoblasts. The activity and yield rate of osteoblasts in type I group are higher which could provide more stable seed cells for the treatment of osteoporosis.

Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes.

PubMed

Müller, A; Linke, W; Klaus, W

1999-05-01

Crataegus extract is used in cardiology for the treatment of mild to moderate heart failure (NYHA II) in Germany. However, little is known about the electrophysiological actions of Crataegus extract in the heart. Recently, it was shown that Crataegus extract prolongs the refractory period in isolated perfused hearts and increases action potential duration in guinea pig papillary muscle. It was the aim of this study to find out the mechanism of the increase in action potential duration caused by Crataegus extract. Using the patch-clamp technique, we measured the effects of Crataegus extract (10 mg/l; flavonoid content: 2.25%, total procyanidin content: 11.3 +/- 0.4%) on the inward rectifier and the delayed rectifier potassium current in isolated guinea pig ventricular myocytes. To get some insight into the mechanism underlying the positive inotropic effect of Crataegus extract, we also looked for effects on the L-type calcium current. Crataegus extract slightly blocked both the delayed and the inward rectifier potassium current. The inhibition amounted to 25% and about 15%, respectively. This amount of inhibition of these repolarising currents is sufficient to explain the prolongation of action potential duration caused by Crataegus extract. To our surprise we could not detect any influence of Crataegus extract on the L-type calcium current. In summary, our results show that Crataegus extract blocks repolarising potassium currents in ventricular myocytes. This effect is similar to the action of class III antiarrhythmic drugs and might be the basis of the antiarrhythmic effects described for Crataegus extract. Our measurements of the L-type calcium current indicate that Crataegus extract's positive inotropic effect is not caused by phosphodiesterase inhibition or a beta-sympathomimetic effect.

Inhibition of bone resorption in vitro by antisense RNA and DNA molecules targeted against carbonic anhydrase II or two subunits of vacuolar H(+)-ATPase.

PubMed Central

Laitala, T; Väänänen, H K

1994-01-01

The bone resorbing cells, osteoclasts, express high levels of carbonic anhydrase II (CA II) and vacuolar H(+)-ATPase (V-ATPase) during bone resorption. We have used antisense RNA and DNA molecules targeted against CA II, and against 16- and 60-kD subunits of vacuolar H(+)-ATPase (V-ATPase), to block the expression of these proteins in vitro. Osteoclastic bone resorption was studied in two in vitro culture systems: release of 45Calcium from prelabeled newborn mouse calvaria cultures, and resorption pit assays performed with rat osteoclasts cultured on bovine bone slices. Both antisense RNA and DNA against CA II and the V-ATPase were used to compare their specificities as regards inhibiting bone resorption in vitro. The antisense molecules inhibited the synthesis of these proteins by decreasing the amounts of mRNA in the cells in a highly specific manner. In osteoclast cultures treated with the 16-kD V-ATPase antisense RNA, acidification of an unknown population of intracellular vesicles was highly stimulated. The acidification of these vesicles was not sensitive to amiloride or bafilomycin A1. This suggests the existence of a back-up system for acidification of intracellular vesicles, when the expression of the V-ATPase is blocked. Our results further indicate that blocking the expression of CA II and V-ATPase with antisense RNA or DNA leads to decreased bone resorption. Images PMID:8200964

Subsurface Implications of Spatially Variable Seafloor Character on the Atlantis Massif

NASA Astrophysics Data System (ADS)

Greene, J. A.; Tominaga, M.; Blackman, D. K.

2014-12-01

We documented and mapped the characteristics of the seafloor on the Atlantis Massif, an ocean core complex located at 30°N on the Mid-Atlantic Ridge. Our goal is to investigate the implications of these surficial features, particularly whether their spatial variations might reflect subsurface lithology and geological processes. We utilized data collected during the MARVEL 2000 cruise AT3-60, specifically Alvin videos and rock samples, Argo II digital still photos, and TOBI/DSL-120 side-scan sonar mosaic. The Alvin dives studied occurred over the Central Dome and Eastern Block, which is interpreted as the hanging wall to the detachment that unroofed the dome. We also studied two Argo II dives located over the Central Dome, one over the Eastern Block, and one over the Western Shoulder of the southern dome. The TOBI/DSL-120 side-scan sonar followed a widespread, looped track providing near total coverage of the massif. We classified the character of the seafloor based on imagery, the acoustic reflectivity, and the basic composition of rock samples. To aid in our classification, we merged Argo II still images to produce photo-mosaics displaying tens of meters long transects. We then classified the seafloor as unconsolidated sediment, lithified sediment (a carbonate crust or cap), exposed bedrock, or rubble. To obtain a broader understanding of the Atlantis Massif, we analyzed the distribution of these classes of seafloor. Over the Central Dome and Western Shoulder, we found most seafloor classes present in notable amounts, with many individual areas dominated by a particular type.

Potential forensic use of a 33 X-InDel panel in the Argentinean population.

PubMed

Caputo, Mariela; Amador, M A; Santos, S; Corach, D

2017-01-01

Polymorphic genetic markers located on the X chromosome might become a complement in particular forensic identification when the biological kinship are deficient. We analyzed forensic statistical parameters of 33 X-chromosome InDel polymorphisms in a sample of 320 individuals from Argentina. The X-chromosome InDel polymorphism (X-InDel) panel was amplified in a single multiplex PCR reaction. Hardy-Weinberg Equilibrium was determined in the female cohort, whereas the male cohort was used to calculate linkage disequilibrium (LD) tested by an extension of Fisher's exact test, D', and Chi-square values. Regarding LD, 15 markers were organized and grouped into six blocks containing two or three linked loci each, namely block I (MID356-MID357), block II (MID448804-MID3703-MID218), block III (MID3705-MID3706-MID304737), block IV (MID197147-MID3754), block V (MID3664-MID284601-MID103547), and block VI (MID3763-MID3728). The haplotype diversity was higher than 0.99 in all cases. Blocks III and VI showed the highest match probability in the studied population, whereas block II showed the lowest. The accumulated power of discrimination was 99.9999991 % in women and 99.9992925 % in men. The mean exclusion chance in trios and duos were 99.9891736 and 99.6099391 %, respectively. Since 15 markers are associated as haplotypic blocks, for a conservative treatment of the data, statistical evaluation should consider their haplotypic frequencies and the remaining 18 markers can be evaluated as independent loci.

Block 2 Solid Rocket Motor (SRM) conceptual design study. Volume 1: Appendices

NASA Technical Reports Server (NTRS)

1986-01-01

The design studies task implements the primary objective of developing a Block II Solid Rocket Motor (SRM) design offering improved flight safety and reliability. The SRM literature was reviewed. The Preliminary Development and Validation Plan is presented.

A method of the up or down layer development of class II oil reservoirs

NASA Astrophysics Data System (ADS)

Wang, Fulin; Zhao, Yunfei; Fang, Yanjun; Yang, Tao; Gui, Dongxu; Wang, Gang; Feng, Chengcheng

2018-06-01

During the 13th five-year period, class II reservoirs of DaQing Oilfield first layer series development will be fully completed, secondary up or down layer development is facing new well drilling or the use of old we ll pattern network method chosen, need to determine development mode of oil block. In this paper, the system economy model is established, the up and down oil layer of the block is considered as one system, and through the comparison of the two models that new well drilling or the use of old well pattern, we can determine the development mode of the block. And take b1ddd block as an example, determine the block need to use what method to develop in different oil prices. Result show when the oil price is 40/bbl, using exiting well to production, when oil price is 70/bbl., using new drilling development model. The method to fill the theory and methodology on selection about reservoir development mode, can provide technical support for DaQing Oilfield the 14th five-year planning and long-term planning.

Small-Molecule Fluorescent Sensors for Investigating Zinc Metalloneurochemistry

PubMed Central

Nolan, Elizabeth M.; Lippard, Stephen J.

2008-01-01

Conspectus Metal ions are involved in many neurobiological processes relevant to human health and disease. The metalloneurochemistry of Zn(II) is of substantial current interest. Zinc is the second most abundant d-block metal ion in the human brain and its distribution varies, with relatively high concentrations found in the hippocampus. Brain zinc is generally divided into two categories: protein-bound and loosely-bound. The latter pool is also referred to as histochemically observable, chelatable, labile, or mobile zinc. The neurophysiological and neuropathological significance of such mobile Zn(II) remains enigmatic. Studies of Zn(II) distribution, translocation, and function in vivo require tools for its detection. Because Zn(II) has a closed-shell d10 configuration and no convenient spectroscopic signature, fluorescence is a suitable method for monitoring Zn(II) in biological contexts. This Account summarizes work by our laboratory addressing the design, preparation, characterization, and use of small-molecule fluorescent sensors for imaging mobile Zn(II) in living cells and samples of brain tissue. These sensors provide “turn-on” or ratiometric Zn(II) detection in aqueous solution at neutral pH. By making alterations to the Zn(II)-binding unit and fluorophore platform, we have devised sensors with varied photophysical and metal-binding properties. We used several of these probes to image Zn(II) distribution, uptake, and mobilization in a variety of cell types, including neuronal cultures. Goals for the future include developing strategies for multi-color imaging, further defining the quenching and turn-on mechanisms of the sensors, and employing the probes to elucidate the functional significance of Zn(II) in neurobiology. PMID:18989940

HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy.

PubMed

Huang, Chih-Yang; Lee, Fa-Lun; Peng, Shu-Fen; Lin, Kuan-Ho; Chen, Ray-Jade; Ho, Tsung-Jung; Tsai, Fu-Jen; Padma, Vijaya V; Kuo, Wei-Wen; Huang, Chih-Yang

2018-02-01

Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT 1 R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1 S303 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II-induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. © 2017 Wiley Periodicals, Inc.

Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hama, Kouji; Ohnishi, Hirohide; Aoki, Hiroyoshi

2006-02-17

Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-{beta}{sub 1} inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-{beta}{sub 1}-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-{beta}{sub 1}-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSCmore » proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-{beta}{sub 1}-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway.« less

Reticulated shallow etch mesa isolation for controlling surface leakage in GaSb-based infrared detectors

NASA Astrophysics Data System (ADS)

Nolde, J. A.; Jackson, E. M.; Bennett, M. F.; Affouda, C. A.; Cleveland, E. R.; Canedy, C. L.; Vurgaftman, I.; Jernigan, G. G.; Meyer, J. R.; Aifer, E. H.

2017-07-01

Longwave infrared detectors using p-type absorbers composed of InAs-rich type-II superlattices (T2SLs) nearly always suffer from high surface currents due to carrier inversion on the etched sidewalls. Here, we demonstrate reticulated shallow etch mesa isolation (RSEMI): a structural method of reducing surface currents in longwave single-band and midwave/longwave dual-band detectors with p-type T2SL absorbers. By introducing a lateral shoulder to increase the separation between the n+ cathode and the inverted absorber surface, a substantial barrier to surface electron flow is formed. We demonstrate experimentally that the RSEMI process results in lower surface current, lower net dark current, much weaker dependence of the current on bias, and higher uniformity compared to mesas processed with a single deep etch. For the structure used, a shoulder width of 2 μm is sufficient to block surface currents.

Pectoral nerve block (Pecs block) with sedation for breast conserving surgery without general anesthesia.

PubMed

Moon, Eun-Jin; Kim, Seung-Beom; Chung, Jun-Young; Song, Jeong-Yoon; Yi, Jae-Woo

2017-09-01

Most regional anesthesia in breast surgeries is performed as postoperative pain management under general anesthesia, and not as the primary anesthesia. Regional anesthesia has very few cardiovascular or pulmonary side-effects, as compared with general anesthesia. Pectoral nerve block is a relatively new technique, with fewer complications than other regional anesthesia. We performed Pecs I and Pec II block simultaneously as primary anesthesia under moderate sedation with dexmedetomidine for breast conserving surgery in a 49-year-old female patient with invasive ductal carcinoma. Block was uneventful and showed no complications. Thus, Pecs block with sedation could be an alternative to general anesthesia for breast surgeries.

Risk of advanced heart block during extradural anaesthesia in patients with right bundle branch block and left anterior hemiblock.

PubMed

Coriat, P; Harari, A; Ducardonet, A; Tarot, J P; Viars, P

1981-05-01

Electrocardiographic recording by Holter monitoring demonstrated the absence of any modification, however minimal, of the intranodal conduction during surgical procedures under extradural anaesthesia in 20 patients with right bundle branch block (RBBB) and left anterior hemiblock (LAHB) but without symptoms. These data suggest that extradural anaesthesia can be used safely in patients with asymptomatic chronic RBBB and LAHB without prophylactic insertion of pacemakers. However, patients having experienced either syncope or transient Mobitz II second degree AV block are likely to have a trifascicular block and increased risk of advanced heart block during extradural anaesthesia.

The coordination chemistry of dipyridylbenzene: N-deficient terpyridine or panacea for brightly luminescent metal complexes?

PubMed

Williams, J A Gareth

2009-06-01

1,3-Di(2-pyridyl)benzene (dpybH) structurally resembles the widely-used ligand terpyridine (tpy), with which it is isoelectronic. In this critical review, following a brief overview of synthetic strategies for dpybH and derivatives, we survey the different types of complex that are possible with these ligands. Whilst metals such as ruthenium(ii), osmium(ii) and platinum(ii) give a terdentate N--C--N binding mode in which cyclometallation occurs at C(2), the ions iridium(iii), rhodium(iii) and palladium(ii) favour C(4) metallation. The latter process can be blocked by appropriate ligand modification, to allow the N--C--N mode to be accessed with these metal ions too. The luminescence properties of the complexes are discussed. A huge range of emission efficiencies are encountered amongst Ir(iii) complexes containing dpyb derivatives, according to the other ligands present. Trends can be rationalised with the aid of simple frontier-orbital considerations. The Pt(ii) complexes of dipyridylbenzenes are also intensely luminescent. Their application to contemporary organic light-emitting device (OLED) technology is discussed, including white light emitters exploiting excimer emission. Their potential as cell imaging agents amenable to time-resolved detection procedures on the microsecond timescale has also been demonstrated (118 references).

Tunable PhoXonic Band Gap Materials from Self-Assembly of Block Copolymers and Colloidal Nanocrystals (NBIT Phase II)

DTIC Science & Technology

2013-12-12

their application in sensors and as displays. We found that the thermochromic behavior of a lamellar block copolymer poly(styrene-b-2-vinylpyridine...the solution pH. The findings of this work provide the basis for understanding and controlling the properties of thermochromic block copolymers...by the glassy PS layers . The glassy layers completely constrain the lateral expansion of the P2VP gel block and the dislocation defect network that

The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation.

PubMed

Xiao, Yucheng; Blumenthal, Kenneth; Jackson, James O; Liang, Songping; Cummins, Theodore R

2010-12-01

The voltage-gated sodium channel Na(v)1.7 plays a crucial role in pain, and drugs that inhibit hNa(v)1.7 may have tremendous therapeutic potential. ProTx-II and huwentoxin-IV (HWTX-IV), cystine knot peptides from tarantula venoms, preferentially block hNa(v)1.7. Understanding the interactions of these toxins with sodium channels could aid the development of novel pain therapeutics. Whereas both ProTx-II and HWTX-IV have been proposed to preferentially block hNa(v)1.7 activation by trapping the domain II voltage-sensor in the resting configuration, we show that specific residues in the voltage-sensor paddle of domain II play substantially different roles in determining the affinities of these toxins to hNa(v)1.7. The mutation E818C increases ProTx-II's and HWTX-IV's IC(50) for block of hNa(v)1.7 currents by 4- and 400-fold, respectively. In contrast, the mutation F813G decreases ProTx-II affinity by 9-fold but has no effect on HWTX-IV affinity. It is noteworthy that we also show that ProTx-II, but not HWTX-IV, preferentially interacts with hNa(v)1.7 to impede fast inactivation by trapping the domain IV voltage-sensor in the resting configuration. Mutations E1589Q and T1590K in domain IV each decreased ProTx-II's IC(50) for impairment of fast inactivation by ~6-fold. In contrast mutations D1586A and F1592A in domain-IV increased ProTx-II's IC(50) for impairment of fast inactivation by ~4-fold. Our results show that whereas ProTx-II and HWTX-IV binding determinants on domain-II may overlap, domain II plays a much more crucial role for HWTX-IV, and contrary to what has been proposed to be a guiding principle of sodium channel pharmacology, molecules do not have to exclusively target the domain IV voltage-sensor to influence sodium channel inactivation.

Condensin II Alleviates DNA Damage and Is Essential for Tolerance of Boron Overload Stress in Arabidopsis[W

PubMed Central

Sakamoto, Takuya; Inui, Yayoi Tsujimoto; Uraguchi, Shimpei; Yoshizumi, Takeshi; Matsunaga, Sachihiro; Mastui, Minami; Umeda, Masaaki; Fukui, Kiichi; Fujiwara, Toru

2011-01-01

Although excess boron (B) is known to negatively affect plant growth, its molecular mechanism of toxicity is unknown. We previously isolated two Arabidopsis thaliana mutants, hypersensitive to excess B (heb1-1 and heb2-1). In this study, we found that HEB1 and HEB2 encode the CAP-G2 and CAP-H2 subunits, respectively, of the condensin II protein complex, which functions in the maintenance of chromosome structure. Growth of Arabidopsis seedlings in medium containing excess B induced expression of condensin II subunit genes. Simultaneous treatment with zeocin, which induces DNA double-strand breaks (DSBs), and aphidicolin, which blocks DNA replication, mimicked the effect of excess B on root growth in the heb mutants. Both excess B and the heb mutations upregulated DSBs and DSB-inducible gene transcription, suggesting that DSBs are a cause of B toxicity and that condensin II reduces the incidence of DSBs. The Arabidopsis T-DNA insertion mutant atr-2, which is sensitive to replication-blocking reagents, was also sensitive to excess B. Taken together, these data suggest that the B toxicity mechanism in plants involves DSBs and possibly replication blocks and that plant condensin II plays a role in DNA damage repair or in protecting the genome from certain genotoxic stressors, particularly excess B. PMID:21917552

Postoperative analgesic efficacy of ultrasound-guided ilioinguinal-iliohypogastric nerve block compared with medial transverse abdominis plane block in inguinal hernia repair: A prospective, randomised trial.

PubMed

Bhatia, Nidhi; Sen, Indu Mohini; Mandal, Banashree; Batra, Ankita

2018-03-29

Analgesic efficacy of ultrasound-guided transverse abdominis plane block, administered a little more medially, just close to the origin of the transverse abdominis muscle has not yet been investigated in patients undergoing unilateral inguinal hernia repair. We hypothesised that medial transverse abdominis plane block would provide comparable postoperative analgesia to ilioinguinal-iliohypogastric nerve block in inguinal hernia repair patients. This prospective, randomised trial was conducted in 50 ASA I and II male patients≥18 years of age. Patients were randomised into two groups to receive either pre-incisional ipsilateral ultrasound-guided ilioinguinal-iliohypogastric nerve block or medial transverse abdominis plane block, with 0.3ml/kg of 0.25% bupivacaine. Our primary objective was postoperative 24-hour analgesic consumption and secondary outcomes included pain scores, time to first request for rescue analgesic and side effects, if any, in the postoperative period. There was no significant difference in the total postoperative analgesic consumption [group I: 66.04mg; group II: 68.33mg (P value 0.908)]. Time to first request for rescue analgesic was delayed, though statistically non-significant (P value 0.326), following medial transverse abdominis plane block, with excellent pain relief seen in 58.3% patients as opposed to 45.8% patients in ilioinguinal-iliohypogastric nerve block group. Medial transverse abdominis plane block being a novel, simple and easily performed procedure can serve as an useful alternative to ilioinguinal-iliohypogastric nerve block for providing postoperative pain relief in inguinal hernia repair patients. Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels.

PubMed

Liu, Dong-Dong; Lu, Jun-Mei; Zhao, Qian-Ru; Hu, Changlong; Mei, Yan-Ai

2016-06-29

Growth differentiation factor-15 (GDF-15) has been implicated in ischemic brain injury and synapse development, but its involvement in modulating neuronal excitability and synaptic transmission remain poorly understood. In this study, we investigated the effects of GDF-15 on non-evoked miniature excitatory post-synaptic currents (mEPSCs) and neurotransmitter release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with GDF-15 for 60 min significantly increased the frequency of mEPSCs without effect on their amplitude. GDF-15 also significantly elevated presynaptic glutamate release, as shown by HPLC. These effects were blocked by dual TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII) antagonists, but not by a TβRI antagonist alone. Meanwhile, GDF-15 enhanced pERK level, and inhibition of MAPK/ERK activity attenuated the GDF-15-induced increases in mEPSC and glutamate release. Blocking T-type calcium channels reduced the GDF-15 induced up-regulation of synaptic transmission. Membrane-protein extraction and use of an intracellular protein-transport inhibitor showed that GDF-15 promoted CaV3.1 and CaV3.3 α-subunit expression by trafficking to the membrane. These results confirm previous findings in cerebellar granule neurons, in which GDF-15 induces its neurobiological effects via TβRII and activation of the ERK pathway, providing novel insights into the mechanism of GDF-15 function in cortical neurons.

Epidemiological studies on Salmonella in a certain area ("Walcheren project"). I. The presence of Salmonella in man, pigs, insects, seagulls and in foods and effluents.

PubMed

Edel, W; van Schothorst, M; Kampelmacher, E H

1976-08-01

During a certain period various materials (pigs, foods, insects, seagull droppings, chopping-block scrapings from butcher's shops, effluents of sewage treatment plants and stools of patients) were examined for the presence of Salmonella at the same time in a relatively small area (Walcheren). Certain types of Salmonella (S. typhi murium type II 505, S. panama, S. infantis and S. brandenburg) were frequently isolated from almost all materials examined. This may indicate the existence of Salmonella contamination cycles: one may think of the cycle: slaughter animal (infected from the environment and/or by meal) - meat - consumer - patient or healthy carrier - effluent and surface water - insects, birds and rodents - slaughter animal or meat and possibly other foods - consumer.

31 CFR 500.205 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... FOREIGN ASSETS CONTROL REGULATIONS Prohibitions § 500.205 Holding of certain types of blocked property in... amounts involved. (h) The following types of property are subject to paragraphs (a) and (b) of this... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Holding of certain types of blocked...

The role of BST2/tetherin in infection with the feline retroviruses

PubMed Central

Dietrich, Isabelle; Hosie, Margaret J.; Willett, Brian J.

2014-01-01

The recently identified host restriction factor tetherin (BST-2, CD317) potently inhibits the release of nascent retrovirus particles from infected cells. Recently, we reported the identification and characterization of tetherin as a novel feline retroviral restriction factor. Based on homology to human tetherin we identified a putative tetherin gene in the genome of the domestic cat (Felis catus) which was found to be expressed in different feline cell lines both prior to and post treatment with either type I or type II interferon (IFN). The predicted structure of feline tetherin (feTHN) was that of a type II single-pass transmembrane protein encoding an N-terminal transmembrane anchor, central predicted coiled-coil bearing extracellular domain to promote dimerization, and a C-terminal GPI-anchor, consistent with conservation of structure between human and feline tetherin. FeTHN displayed potent inhibition of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) particle release in single-cycle replication assays. Notably, feTHN activity was resistant to antagonism by HIV-1 Vpu. However, stable ectopic expression of feTHN mRNA in different feline cell lines had no inhibitory effect on the growth of diverse primary or cell culture-adapted strains of FIV. Hence, whereas feline tetherin efficiently blocks viral particle release in single-cycle replication assays, it might not prevent dissemination of feline retroviruses in vivo. PMID:21715020

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model.

PubMed

Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

2016-06-07

Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/-mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/-mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/-mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/-mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/-mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model

PubMed Central

Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

2016-01-01

Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/−mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/−mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/−mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/−mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/−mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer. PMID:27145454

Mechanisms of efferent-mediated responses in the turtle posterior crista.

PubMed

Holt, Joseph C; Lysakowski, Anna; Goldberg, Jay M

2006-12-20

To study the cellular mechanisms of efferent actions, we recorded from vestibular-nerve afferents close to the turtle posterior crista while efferent fibers were electrically stimulated. Efferent-mediated responses were obtained from calyx-bearing (CD, calyx and dimorphic) afferents and from bouton (B) afferents distinguished by their neuroepithelial locations into BT units near the torus and BM units at intermediate sites. The spike discharge of CD units is strongly excited by efferent stimulation, whereas BT and BM units are inhibited, with BM units also showing a postinhibitory excitation. Synaptic activity was recorded intracellularly after spikes were blocked. Responses of BT/BM units to single efferent shocks consist of a brief depolarization followed by a prolonged hyperpolarization. Both components reflect variations in hair-cell quantal release rates and are eliminated by pharmacological antagonists of alpha9/alpha10 nicotinic receptors. Blocking calcium-dependent SK potassium channels converts the biphasic response into a prolonged depolarization. Results can be explained, as in other hair-cell systems, by the sequential activation of alpha9/alpha10 and SK channels. In BM units, the postinhibitory excitation is based on an increased rate of hair-cell quanta and depends on the preceding inhibition. There is, in addition, an efferent-mediated, direct depolarization of BT/BM and CD fibers. In CD units, it is the exclusive efferent response. Nicotinic antagonists have different effects on hair-cell efferent actions and on the direct depolarization of CD and BT/BM units. Ultrastructural studies, besides confirming the efferent innervation of type II hair cells and calyx endings, show that turtle efferents commonly contact afferent boutons terminating on type II hair cells.

In Zucker Diabetic Fatty rats, subclinical diabetic neuropathy increases in vivo lidocaine block duration but not in vitro neurotoxicity

PubMed Central

Lirk, Philipp; Flatz, Magdalena; Haller, Ingrid; Hausott, Barbara; Blumenthal, Stephan; Stevens, Markus F.; Suzuki, Suzuko; Klimaschewski, Lars; Gerner, Peter

2012-01-01

Background and Objectives Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. Additionally, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity in vitro and block duration in vivo in a genetic animal model of diabetes mellitus type II. Methods In the first experiments, neurons harvested from control Zucker Diabetic Fatty (ZDF) rats were exposed to acute (24 hours) or chronic (72 hours) hyperglycemia, followed by incubation with lidocaine 40 mM (approximately 1%). In a second experiment, neurons harvested from control ZDF rats, or diabetic ZDF rats, were incubated with lidocaine, with or without SB203580, an inhibitor of the p38 Mitogen-Activated Protein Kinase. Finally, we performed sciatic nerve block (lidocaine 2%, 0.2 mL) in control or diabetic ZDF rats, and measured motor and nociceptive block duration. Results In vitro, neither acute nor chronic hyperglycemia altered neurotoxic properties of lidocaine. In vitro, incubation of neurons with lidocaine resulted in a slightly decreased survival ratio when neurons were harvested from diabetic (57 ± 19) as compared to control (64 ± 9 %) rats. The addition of SB203580 partly reversed this enhanced neurotoxic effect and raised survival to 71 ± 12 in diabetic and 66 ± 9 % in control rats, respectively. In vivo, even though no difference was detected at baseline testing, motor block was significantly prolonged in diabetic as compared to control rats (137 ± 16 min versus 86 ± 17 min). Conclusions In vitro, local anesthetic neurotoxicity was more pronounced on neurons from diabetic animals, but the survival difference was small. In vivo, subclinical neuropathy leads to substantial prolongation of block duration. We conclude that early diabetic neuropathy increases block duration, while the observed increase in toxicity was small. PMID:23011115

Toll-like receptor agonists are potent inhibitors of human immunodeficiency virus-type 1 replication in peripheral blood mononuclear cells.

PubMed

Buitendijk, Maarten; Eszterhas, Susan K; Howell, Alexandra L

2014-05-01

Innate immune responses to microbial pathogens are initiated following the binding of ligand to specific pattern recognition receptors. Each pattern recognition receptor, which includes members of the Toll-like receptor (TLR) family, is specific for a particular type of pathogen associated molecular pattern ensuring that the organism can respond rapidly to a wide range of pathogens including bacteria, viruses, and fungi. We studied the extent to which agonists to endosomal TLR could induce anti-HIV-1 activity in peripheral blood mononuclear cells (PBMCs). When agonists to TLR3, TLR7, TLR8 and TLR9 were added prior to infection with HIV-1, they significantly reduced infection of peripheral blood mononuclear cells. Interestingly, agonists to TLR8 and TLR9 were highly effective at blocking HIV replication even when added as late as 48 h or 72 h, respectively, after HIV-1 infection, indicating that the anti-viral effect was durable and long lasting. Analysis of the induction of anti-viral genes after agonist activation of TLR indicated that all of the agonists induced expression of the type I interferons and interferon stimulated genes, although to variable levels that depended on the agonist used. Interestingly, only the agonist to TLR9, ODN2395 DNA, induced expression of type II interferon and the anti-HIV proteins Apobec3G and SAMHD1. By blocking TLR activity using an inhibitor to the MyD88 adaptor protein, we demonstrated that, at least for TLR8 and TLR9, the anti-HIV activity was not entirely mediated by TLR activation, but likely by the activation of additional anti-viral sensors in HIV target cells. These findings suggest that agonists to the endosomal TLR function to induce expression of anti-HIV molecules by both TLR-mediated and non-TLR-mediated mechanisms. Moreover, the non-TLR-mediated mechanisms induced by these agonists could potentially be exploited to block HIV-1 replication in recently HIV-exposed individuals.

31 CFR 515.205 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CUBAN ASSETS CONTROL REGULATIONS Prohibitions § 515.205 Holding of certain types of blocked property in... involved. (h) The following types of property are subject to paragraphs (a) and (b) of this section: (1... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Holding of certain types of blocked...

31 CFR 515.205 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CUBAN ASSETS CONTROL REGULATIONS Prohibitions § 515.205 Holding of certain types of blocked property in... involved. (h) The following types of property are subject to paragraphs (a) and (b) of this section: (1... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Holding of certain types of blocked...

31 CFR 515.205 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CUBAN ASSETS CONTROL REGULATIONS Prohibitions § 515.205 Holding of certain types of blocked property in... involved. (h) The following types of property are subject to paragraphs (a) and (b) of this section: (1... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Holding of certain types of blocked...

31 CFR 515.205 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2012 CFR

2012-07-01

... CUBAN ASSETS CONTROL REGULATIONS Prohibitions § 515.205 Holding of certain types of blocked property in... involved. (h) The following types of property are subject to paragraphs (a) and (b) of this section: (1... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Holding of certain types of blocked...

31 CFR 515.205 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2014 CFR

2014-07-01

... CUBAN ASSETS CONTROL REGULATIONS Prohibitions § 515.205 Holding of certain types of blocked property in... involved. (h) The following types of property are subject to paragraphs (a) and (b) of this section: (1... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Holding of certain types of blocked...

The Molecular Cytogenetic Characterization of Pistachio (Pistacia vera L.) Suggests the Arrest of Recombination in the Largest Heteropycnotic Pair HC1.

PubMed

Sola-Campoy, Pedro J; Robles, Francisca; Schwarzacher, Trude; Ruiz Rejón, Carmelo; de la Herrán, Roberto; Navajas-Pérez, Rafael

2015-01-01

This paper represents the first molecular cytogenetic characterization of the strictly dioecious pistachio tree (Pistacia vera L.). The karyotype was characterized by fluorescent in situ hybridization (FISH) with probes for 5S and 45S rDNAs, and the pistachio specific satellite DNAs PIVE-40, and PIVE-180, together with DAPI-staining. PIVE-180 has a monomeric unit of 176-178 bp and high sequence homology between family members; PIVE-40 has a 43 bp consensus monomeric unit, and is most likely arranged in higher order repeats (HORs) of two units. The P. vera genome is highly heterochromatic, and prominent DAPI positive blocks are detected in most chromosomes. Despite the difficulty in classifying chromosomes according to morphology, 10 out of 15 pairs (2n = 30) could be distinguished by their unique banding patterns using a combination of FISH probes. Significantly, the largest pair, designated HC1, is strongly heteropycnotic, shows differential condensation, and has massive enrichment in PIVE-40 repeats. There are two types of HC1 chromosomes (type-I and type-II) with differing PIVE-40 hybridization signal. Only type-I/II heterozygotes and type-I homozygotes individuals were found. We speculate that the differentiation between the two HC1 chromosomes is due to suppression of homologous recombination at meiosis, reinforced by the presence of PIVE-40 HORs and differences in PIVE-40 abundance. This would be compatible with a ZW sex-determination system in the pistachio tree.

The Molecular Cytogenetic Characterization of Pistachio (Pistacia vera L.) Suggests the Arrest of Recombination in the Largest Heteropycnotic Pair HC1

PubMed Central

Sola-Campoy, Pedro J.; Robles, Francisca; Schwarzacher, Trude; Ruiz Rejón, Carmelo; de la Herrán, Roberto; Navajas-Pérez, Rafael

2015-01-01

This paper represents the first molecular cytogenetic characterization of the strictly dioecious pistachio tree (Pistacia vera L.). The karyotype was characterized by fluorescent in situ hybridization (FISH) with probes for 5S and 45S rDNAs, and the pistachio specific satellite DNAs PIVE-40, and PIVE-180, together with DAPI-staining. PIVE-180 has a monomeric unit of 176–178 bp and high sequence homology between family members; PIVE-40 has a 43 bp consensus monomeric unit, and is most likely arranged in higher order repeats (HORs) of two units. The P. vera genome is highly heterochromatic, and prominent DAPI positive blocks are detected in most chromosomes. Despite the difficulty in classifying chromosomes according to morphology, 10 out of 15 pairs (2n = 30) could be distinguished by their unique banding patterns using a combination of FISH probes. Significantly, the largest pair, designated HC1, is strongly heteropycnotic, shows differential condensation, and has massive enrichment in PIVE-40 repeats. There are two types of HC1 chromosomes (type-I and type-II) with differing PIVE-40 hybridization signal. Only type-I/II heterozygotes and type-I homozygotes individuals were found. We speculate that the differentiation between the two HC1 chromosomes is due to suppression of homologous recombination at meiosis, reinforced by the presence of PIVE-40 HORs and differences in PIVE-40 abundance. This would be compatible with a ZW sex-determination system in the pistachio tree. PMID:26633808

The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

PubMed Central

Brabletz, T; Pietrowski, I; Serfling, E

1991-01-01

Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism. Images PMID:1707162

The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

PubMed

Brabletz, T; Pietrowski, I; Serfling, E

1991-01-11

Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism.

Ligand reprogramming in dinuclear helicate complexes: a consequence of allosteric or electrostatic effects?

PubMed

Jeffery, John C; Rice, Craig R; Harding, Lindsay P; Baylies, Christian J; Riis-Johannessen, Thomas

2007-01-01

The ditopic ligand 6,6'-bis(4-methylthiazol-2-yl)-3,3'-([18]crown-6)-2,2'-bipyridine (L(1)) contains both a potentially tetradentate pyridyl-thiazole (py-tz) N-donor chain and an additional "external" crown ether binding site which spans the central 2,2'-bipyridine unit. In polar solvents (MeCN, MeNO(2)) this ligand forms complexes with Zn(II), Cd(II), Hg(II) and Cu(I) ions via coordination of the N donors to the metal ion. Reaction with both Hg(II) and Cu(I) ions results in the self-assembly of dinuclear double-stranded helicate complexes. The ligands are partitioned by rotation about the central py--py bond, such that each can coordinate to both metals as a bis-bidentate donor ligand. With Zn(II) ions a single-stranded mononuclear species is formed in which one ligand coordinates the metal ion in a planar tetradentate fashion. Reaction with Cd(II) ions gives rise to an equilibrium between both the dinuclear double-stranded helicate and the mononuclear species. These complexes can further coordinate s-block metal cations via the remote crown ether O-donor domains; a consequence of which are some remarkable changes in the binding modes of the N-donor domains. Reaction of the Hg(II)- or Cd(II)-containing helicate with either Ba(2+) or Sr(2+) ions effectively reprogrammes the ligand to form only the single-stranded heterobinuclear complexes [MM'(L(1))](4+) (M=Hg(II), Cd(II); M'=Ba(2+), Sr(2+)), where the transition and s-block cations reside in the N- and O-donor sites, respectively. In contrast, the same ions have only a minor structural impact on the Zn(II) species, which already exists as a single-stranded mononuclear complex. Similar reactions with the Cd(II) system result in a shift in equilibrium towards the single-stranded species, the extent of which depends on the size and charge of the s-block cation in question. Reaction of the dicopper(I) double-stranded helicate with Ba(2+) shows that the dinuclear structure still remains intact but the pitch length is significantly increased.

Modelling of the Vajont rockslide displacements by delayed plasticity of interacting sliding blocks

NASA Astrophysics Data System (ADS)

Castellanza, riccardo; Hedge, Amarnath; Crosta, Giovanni; di Prisco, Claudio; Frigerio, Gabriele

2015-04-01

In order to model complex sliding masses subject to continuous slow movements related to water table fluctuations it is convenient to: i) model the time-dependent mechanical behaviour of the materials by means of a viscous-plastic constitutive law; ii) assume the water table fluctuation as the main input to induce displacement acceleration; iii) consider, the 3D constrains by maintaining a level of simplicity such to allow the implementation into EWS (Early Warning System) for risk management. In this work a 1D pseudo-dynamic visco-plastic model (Secondi et al. 2011), based on Perzyna's delayed plasticity theory is applied. The sliding mass is considered as a rigid block subject to its self weight, inertial forces and seepage forces varying with time. All non-linearities are lumped in a thin layer positioned between the rigid block and the stable bedrock. The mechanical response of this interface is assumed to be visco-plastic. The viscous nucleus is assumed to be of the exponential type, so that irreversible strains develop for both positive and negative values of the yield function; the sliding mass is discretized in blocks to cope with complex rockslide geometries; the friction angle is assumed to reduce with strain rate assuming a sort of strain - rate law (Dietrich-Ruina law). To validate the improvements introduced in this paper the simulation of the displacements of the Vajont rockslide from 1960 to the failure, occurred on October the 9th 1963, is perfomed. It will be shown that, in its modified version, the model satisfactorily fits the Vajont pre-collapse displacements triggered by the fluctuation of the Vajont lake level and the associated groundwater level. The model is able to follow the critical acceleration of the motion with a minimal change in friction properties.The discretization in interacting sliding blocks confirms its suitability to model the complex 3D rockslide behaviour. We are currently implementing a multi-block model capable to include the mutual influence of multiple blocks, characterized by different geometry and groundwater levels, shear zone properties and type of interconnection. Secondi M., Crosta G., Di Prisco C., Frigerio G., Frattini P., Agliardi F. (2011) "Landslide motion forecasting by a dynamic visco-plastic model", Proc. The Second World Landslide Forum, L09 - Advances in slope modelling, Rome, 3-9 October 2011, paper WLF2-2011-0571

Small-angle-neutron-scattering from giant water-in-oil microemulsion droplets. II. Polymer-decorated droplets in a quaternary system

NASA Astrophysics Data System (ADS)

Foster, Tobias; Sottmann, Thomas; Schweins, Ralf; Strey, Reinhard

2008-02-01

Amphiphilic block copolymers of the type poly(ethylenepropylene)-co-poly(ethyleneoxide) dramatically enhance the solubilisation efficiency of non-ionic surfactants in microemulsions that contain equal volumes of water in oil. Consequently, the length scale of the microstructure of such bicontinuous microemulsions is dramatically increased up to the order of a few 100nm. In this paper, we show that this so-called efficiency boosting effect can also be applied to water-in-oil microemulsions with droplet microstructure. Such giant water-in-oil microemulsions would provide confined compartments in which chemical reactions of biological macromolecules can be performed on a single molecule level. With this motivation we investigated the phase behavior and the microstructure of oil-rich microemulsions containing D2O, n-decane(d22), C10E4 and the amphiphilic block copolymer PEP5-PEO5 [poly(ethylenepropylene)-co-poly(ethyleneoxide), weight per block of 5000g/mol]. We found that 15wt% of water can be solubilised by 5wt% of surfactant and block copolymer when about 6wt% of surfactant is replaced by the block copolymer. Small-angle-neutron-scattering experiments were performed to determine the length scales and microstructure topologies of the oil-rich microemulsions. To analyze the scattering data, we derived a novel form factor that also takes into account the scattering contribution of the hydrophobic part of the block copolymer molecules that reside in the surfactant shell. The quantitative analysis of the scattering data with this form factor shows that the radius of the largest droplets amounts up to 30nm. The novel form factor also yielded qualitative information on the stretching of the polymer chains in dependence on the polymer surface density and the droplet radius.

Losartan, an Angiotensin type I receptor, restores erectile function by downregulation of cavernous renin-angiotensin system in streptozocin-induced diabetic rats.

PubMed

Yang, Rong; Yang, Bin; Wen, Yanting; Fang, Feng; Cui, Souxi; Lin, Guiting; Sun, Zeyu; Wang, Run; Dai, Yutian

2009-03-01

The high incidence of erectile dysfunction (ED) in diabetes highlights the need for good treatment strategies. Recent evidence indicates that blockade of the angiotensin type I receptor (AT1) may reverse ED from various diseases. To explore the role of cavernous renin-angiotensin system (RAS) in the pathogenesis of diabetic ED and the role of losartan in the treatment of diabetic ED. The AT1 blocker (ARB) losartan (30 mg/kg/d) was administered to rats with streptozocin (65 mg/kg)-induced diabetes. Erectile function, cavernous structure, and tissue gene and protein expression of RAS in the corpora cavernosa were studied. We sought to determine the changes of cavernous RAS in the condition of diabetes and after treatment with losartan. RAS components (angiotensinogen, [pro]renin receptor, angiotensin-converting enzyme [ACE], and AT1) were expressed in cavernosal tissue. In diabetic rats, RAS components were upregulated, resulting in the increased concentration of angiotensin II (Ang II) in the corpora. A positive feedback loop for Ang II formation in cavernosum was also identified, which could contribute to overactivity of cavernous RAS in diabetic rats. Administration of losartan blocked the effect of Ang II, downregulated the expression of AT1 and Ang II generated locally, and partially restored erectile function (losartan-treated group revealed an improved intracavernous pressure/mean systemic arterial pressure ratio as compared with the diabetic group (0.480 +/- 0.031 vs. 0.329 +/- 0.020, P < 0.01). However, losartan could not elevate the reduced smooth muscle/collagen ratio in diabetic rats. The cavernous RAS plays a role in modulating erectile function in corpora cavernosa and is involved in the pathogenesis of diabetic ED. ARB can restore diabetic ED through downregulating cavernous RAS.

Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

NASA Astrophysics Data System (ADS)

Li, Hewang; Yu, Peiying; Sun, Yuansheng; Felder, Robin A.; Periasamy, Ammasi; Jose, Pedro A.

2010-09-01

The dynamic regulation of the cellular trafficking of human angiotensin (Ang) type 1 receptor (AT1R) is not well understood. Therefore, we investigated the cellular trafficking of AT1R-enhanced green fluorescent protein (EGFP) (AT1R-EGFP) heterologously expressed in HEK293 cells by determining the change in donor lifetime (AT1R-EGFP) in the presence or absence of acceptor(s) using fluorescence lifetime imaging-fluorescence resonance energy transfer (FRET) microscopy. The average lifetime of AT1R-EGFP in our donor-alone samples was ~2.33 ns. The basal state lifetime was shortened slightly in the presence of Rab5 (2.01+/-0.10 ns) or Rab7 (2.11+/-0.11 ns) labeled with Alexa 555, as the acceptor fluorophore. A 5-min Ang II treatment markedly shortened the lifetime of AT1R-EGFP in the presence of Rab5-Alexa 555 (1.78+/-0.31 ns) but was affected minimally in the presence of Rab7-Alexa 555 (2.09+/-0.37 ns). A 30-min Ang II treatment further decreased the AT1R-EGFP lifetime in the presence of both Rab5- and Rab7-Alexa 555. Latrunculin A but not nocodazole pretreatment blocked the ability of Ang II to shorten the AT1R-EGFP lifetime. The occurrence of FRET between AT1R-EGFP (donor) and LAMP1-Alexa 555 (acceptor) with Ang II stimulation was impaired by photobleaching the acceptor. These studies demonstrate that Ang II-induced AT1R lysosomal degradation through its association with LAMP1 is regulated by Rab5/7 via mechanisms that are dependent on intact actin cytoskeletons.

Na8Au9.8(4)Ga7.2 and Na17Au5.87(2)Ga46.63: The diversity of pseudo 5-fold symmetries in the Na-Au-Ga system

NASA Astrophysics Data System (ADS)

Smetana, Volodymyr; Corbett, John D.; Miller, Gordon J.

2013-11-01

The Na-rich part (~30% Na) of the Na-Au-Ga system between NaAu2, NaGa4, and Na22Ga39 has been found to contain the ternary phases Na8Au9.8(4)Ga7.2 (I) and Na17Au5.87(2)Ga46.63 (II), according to the results of single crystal X-ray diffraction measurements. I is orthorhombic, Cmcm, a=5.3040(1), b=24.519(5), c=14.573(3) Å, and contains a network of clusters with local 5-fold symmetry along the a-axis. Such clusters are frequent building units in decagonal quasicrystals and their approximants. II is rhombohedral, R3¯m, a=16.325(2), c=35.242(7) Å, and contains building blocks that are structurally identical to the Bergman-type clusters as well as fused icosahedral units known with active metals, triels and late transition elements. II also contains a polycationic network with elements of the clathrate V type structure. Tight-binding electronic structure calculations using linear muffin-tin-orbital (LMTO) methods on idealized models of I and II indicate that both compounds are metallic with evident pseudogaps at the corresponding Fermi levels. The overall Hamilton bond populations are generally dominated by Au-Ga and Au-Au bonds in I and by Ga-Ga bonds in II; moreover, the Na-Au and Na-Ga contributions in I are unexpectedly large, ~20% of the total. A similar involvement of sodium in covalent bonding has also been found in the electron-richer i-Na13Au12Ga15 quasicrystal approximant.

Replication restart in UV-irradiated Escherichia coli involving pols II, III, V, PriA, RecA and RecFOR proteins.

PubMed

Rangarajan, Savithri; Woodgate, Roger; Goodman, Myron F

2002-02-01

In Escherichia coli, UV-irradiated cells resume DNA synthesis after a transient inhibition by a process called replication restart. To elucidate the role of several key proteins involved in this process, we have analysed the time dependence of replication restart in strains carrying a combination of mutations in lexA, recA, polB (pol II), umuDC (pol V), priA, dnaC, recF, recO or recR. We find that both pol II and the origin-independent primosome-assembling function of PriA are essential for the immediate recovery of DNA synthesis after UV irradiation. In their absence, translesion replication or 'replication readthrough' occurs approximately 50 min after UV and is pol V-dependent. In a wild-type, lexA+ background, mutations in recF, recO or recR block both pathways. Similar results were obtained with a lexA(Def) recF strain. However, lexA(Def) recO or lexA(Def) recR strains, although unable to facilitate PriA-pol II-dependent restart, were able to perform pol V-dependent readthrough. The defects in restart attributed to mutations in recF, recO or recR were suppressed in a recA730 lexA(Def) strain expressing constitutively activated RecA (RecA*). Our data suggest that in a wild-type background, RecF, O and R are important for the induction of the SOS response and the formation of RecA*-dependent recombination intermediates necessary for PriA/Pol II-dependent replication restart. In con-trast, only RecF is required for the activation of RecA that leads to the formation of pol V (UmuD'2C) and facilitates replication readthrough.

A preliminary study of genetic diversity of MSP-1 types in Plasmodium falciparum in southern province of Sistan Baluchistan of Iran.

PubMed

Zahra, Zamani; Reza, Razavi Mohammad; Mehdi, Assmar; Sedigheh, Sadeghi; Fatemeh, Pourfallah; Nikoo, Nasoohi; Ashraf, Sheibani; Mohammad, Raisi

2007-02-01

Plasmodiumfalciparum merozoite surface protein-1 (MSP-1) shows extensive antigenic diversity. This is due to the presence of seven variable blocks, five semi-conserved and also five conserved blocks. The variable blocks in the MSP-1 gene are principally dimorphic, displaying either K1 or MAD20 type; except for the block 2 region which is represented by three alleles, an RO33 type in addition to the other two. Allelic diversity is reported to be generated by intra-genic recombination between the variable blocks. A study of allelic variation of MSP-1 gene in Plasmodium falciparum was carried out in the southern province of Sistan Baluchistan in Iran in 2001-2003. Samples were obtained from 30 febrile patients and DNA was extracted and association types between blocks 2 and 6 was identified on each block using specific primers and compared with those from Vietnam, Brazil and Africa. The association types obtained, were similar though less in number than the ones from Vietnam, but more than those from Africa and Brazil.

Reinforcement of subarachnoid block by epidural volume effect in lower abdominal surgery: A comparison between fentanyl and tramadol for efficacy and block properties

PubMed Central

Mohan, Atiharsh; Singh, Preet Mohinder; Malviya, Deepak; Arya, Sunil Kumar; Singh, Dinesh Kumar

2012-01-01

Background: Epidural volume extension (EVE) is claimed to increase the block height and decrease the dose requirement for intrathecal drug. However, almost all studies have been done in obstetric population and none actually compares the effect of additional drugs added to epidural volume. Materials and Methods: Seventy-five (ASA I and II) patients scheduled for lower abdominal surgery were randomly divided into three groups. All groups received intrathecal 10 mg bupivacaine; two groups received additional 10 ml of normal saline epidurally with 25 mg tramadol or 25 mg of fentanyl. Groups were than compared for maximal block height, rate of sensory block regression to T10, and motor block regression to Bromage scale of 0. Time to first analgesia and adverse effects were also compared among the three groups. Materials and Methods: Seventy-five (ASA I and II) patients scheduled for lower abdominal surgery were randomly divided into three groups. All groups received intrathecal 10 mg bupivacaine; two groups received additional 10 ml of normal saline epidurally with 25 mg tramadol or 25 mg of fentanyl. Groups were than compared for maximal block height, rate of sensory block regression to T10, and motor block regression to Bromage scale of 0. Time to first analgesia and adverse effects were also compared among the three groups. Results: Groups with EVE had statistically significant higher block height, with a significant faster regression that the control group. However, both fentanyl and tramadol groups were inseparable in respect to motor or sensory block regression. Fentanyl group had maximal time to first analgesia, followed by tramadol and control groups. Hemodynamic alterations were also more common in EVE groups. Conclusion: EVE can increase the block height significantly, but it seems to be limited only to the physical property of additional volume in epidural space and fentanyl or tramadol do not seem to differ in their ability to alter block properties. PMID:25885615

Joint Service Chemical and Biological Defense Program. FY00-02 Overview

DTIC Science & Technology

2001-09-01

Development. Contractors: 12 BI DS Biological Integrated Detection System (BIDS) Lead Service Bio Road HERCULES, CA Bruker Analytical Systems BILLERICA, MA...Dynamics Land Systems Division DETROIT, MI Henschel Wehrtechnik GERMANY Bruker -Franzen GERMANY Block II – TBD Milestones Block I MS III (2QFY94) Block...ground. Accessories include hoses and hose reels, two trigger-controlled spray wands , and two electrical-powered scrub brush assemblies. The M22

Pectoral nerve block (Pecs block) with sedation for breast conserving surgery without general anesthesia

PubMed Central

Moon, Eun-Jin; Kim, Seung-Beom; Chung, Jun-Young; Song, Jeong-Yoon

2017-01-01

Most regional anesthesia in breast surgeries is performed as postoperative pain management under general anesthesia, and not as the primary anesthesia. Regional anesthesia has very few cardiovascular or pulmonary side-effects, as compared with general anesthesia. Pectoral nerve block is a relatively new technique, with fewer complications than other regional anesthesia. We performed Pecs I and Pec II block simultaneously as primary anesthesia under moderate sedation with dexmedetomidine for breast conserving surgery in a 49-year-old female patient with invasive ductal carcinoma. Block was uneventful and showed no complications. Thus, Pecs block with sedation could be an alternative to general anesthesia for breast surgeries. PMID:28932733

Collision of the Tacheng block with the Mayile-Barleik-Tangbale accretionary complex in Western Junggar, NW China: Implication for Early-Middle Paleozoic architecture of the western Altaids

NASA Astrophysics Data System (ADS)

Zhang, Ji'en; Xiao, Wenjiao; Luo, Jun; Chen, Yichao; Windley, Brian F.; Song, Dongfang; Han, Chunming; Safonova, Inna

2018-06-01

Western Junggar in NW China, located to the southeast of the Boshchekul-Chingiz (BC) Range and to the north of the Chu-Balkhash-Yili microcontinent (CBY), played a key role in the architectural development of the western Altaids. However, the mutual tectonic relationships have been poorly constrained. In this paper, we present detailed mapping, field structural geology, and geochemical data from the Barleik-Mayile-Tangbale Complex (BMTC) in Western Junggar. The Complex is divisible into Zones I, II and III, which are mainly composed of Cambrian-Silurian rocks. Zone I contains pillow lava, siliceous shale, chert, coral-bearing limestone, sandstone and purple mudstone. Zone II consists of basaltic lava, siliceous shale, chert, sandstone and mudstone. Zone III is characterized by basalt, chert, sandstone and mudstone. These rocks represent imbricated ocean plate stratigraphy, which have been either tectonically juxtaposed by thrusting or form a mélange with a block-in-matrix structure. All these relationships suggest that the BMTC is an Early-Middle Paleozoic accretionary complex in the eastern extension of the BC Range. These Early Paleozoic oceanic rocks were thrust onto Silurian sediments forming imbricate thrust stacks that are unconformably overlain by Devonian limestone, conglomerate and sandstone containing fossils of brachiopoda, crinoidea, bryozoa, and plant stems and leaves. The tectonic vergence of overturned folds in cherts, drag-related curved cleavages and σ-type structures on the main thrust surface suggests top-to-the-NW transport. Moreover, the positive εNd(t) values of volcanic rocks from the Tacan-1 drill-core, and the positive εHf(t) values and post-Cambrian ages of detrital zircons from Silurian and Devonian strata to the south of the Tacheng block indicate that its basement is a depleted and juvenile lithosphere. And there was a radial outward transition from coral-bearing shallow marine (shelf) to deep ocean (pelagic) environments, and from OIB/E-MORB to N-MORB lava geochemistry away from the Tacheng block. Comparisons with published data suggest that these positive isotopic values, stratigraphic, structural and geochemical relationships can be best understood as an analogue of the relationships between the Ontong Java oceanic plateau and the Pacific oceanic crust. Therefore we propose that the basement of the Tacheng block was an Early Paleozoic oceanic plateau. The southern part of the Tacheng block was an accretionary complex and the northern part was an oceanic basin in the Early Paleozoic, the configuration of which is similar to that of the present Ontong Java oceanic plateau situated on the Pacific oceanic crust, and its accretion into the Solomon accretionary complex. The presence of Ordovician SSZ-type ophiolites, early Paleozoic blueschist and Silurian SSZ-type intrusions in the BMTC, and Early-Middle Paleozoic continental arc-related intrusive rocks in the northern margin of the CBY provide further corroboration of a former subduction zone between the southern West Junggar and the northern margin of the CBY. Furthermore, consideration of the fact that the Kokchetav-North Tianshan range was collaged to the southern margin of the CBY in the Ordovician-Devonian indicates that both ranges were amalgamated synchronously with the CBY constructing the Early-Middle Paleozoic architecture of western Altaids.

The TCP4 transcription factor of Arabidopsis blocks cell division in yeast at G1 {yields} S transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aggarwal, Pooja; Padmanabhan, Bhavna; Bhat, Abhay

2011-07-01

Highlights: {yields} TCP4 is a class II TCP transcription factor, that represses cell division in Arabidopsis. {yields} TCP4 expression in yeast retards cell division by blocking G1 {yields} S transition. {yields} Genome-wide expression studies and Western analysis reveals stabilization of cell cycle inhibitor Sic1, as possible mechanism. -- Abstract: The TCP transcription factors control important aspects of plant development. Members of class I TCP proteins promote cell cycle by regulating genes directly involved in cell proliferation. In contrast, members of class II TCP proteins repress cell division. While it has been postulated that class II proteins induce differentiation signal, theirmore » exact role on cell cycle has not been studied. Here, we report that TCP4, a class II TCP protein from Arabidopsis that repress cell proliferation in developing leaves, inhibits cell division by blocking G1 {yields} S transition in budding yeast. Cells expressing TCP4 protein with increased transcriptional activity fail to progress beyond G1 phase. By analyzing global transcriptional status of these cells, we show that expression of a number of cell cycle genes is altered. The possible mechanism of G1 {yields} S arrest is discussed.« less

Fiber Type-Specific Satellite Cell Content in Cyclists Following Heavy Training with Carbohydrate and Carbohydrate-Protein Supplementation

PubMed Central

McKenzie, Alec I.; D'Lugos, Andrew C.; Saunders, Michael J.; Gworek, Keith D.; Luden, Nicholas D.

2016-01-01

The central purpose of this study was to evaluate the fiber type-specific satellite cell and myonuclear responses of endurance-trained cyclists to a block of intensified training, when supplementing with carbohydrate (CHO) vs. carbohydrate-protein (PRO). In a crossover design, endurance-trained cyclists (n = 8) performed two consecutive training periods, once supplementing with CHO (de facto “control” condition) and the other with PRO. Each training period consisted of 10 days of intensified cycle training (ICT–120% increase in average training duration) followed by 10 days of recovery (RVT–reduced volume training; 33% volume reduction vs. normal training). Skeletal muscle biopsies were obtained from the vastus lateralis before and after ICT and again following RVT. Immunofluorescent microscopy was used to quantify SCs (Pax7+), myonuclei (DAPI+), and myosin heavy chain I (MyHC I). Data are expressed as percent change ± 90% confidence limits. The 10-day block of ICTCHO increased MyHC I SC content (35 ± 28%) and myonuclear density (16 ± 6%), which remained elevated following RVTCHO (SC = 69 ± 50% vs. PRE; Nuclei = 17 ± 15% vs. PRE). MyHC II SC and myonuclei were not different following ICTCHO, but were higher following RVTCHO (SC = +33 ± 31% vs. PRE; Nuclei = 15 ± 14% vs. PRE), indicating a delayed response compared to MyHC I fibers. The MyHC I SC pool increased following ICTPRO (37 ± 37%), but without a concomitant increase in myonuclei. There were no changes in MyHC II SC or myonuclei following ICTPRO. Collectively, these trained endurance cyclists possessed a relatively large pool of SCs that facilitated rapid (MyHC I) and delayed (MyHC II) satellite cell proliferation and myonuclear accretion under carbohydrate conditions. The current findings strengthen the growing body of evidence demonstrating alterations in satellite cell number in the absence of hypertrophy. Satellite cell pool expansion is typically viewed as an advantageous response to exercise. However, when coupled with our previous report that PRO possibly enhanced whole muscle recovery and increased MyHC I and II fiber size, the limited satellite cell/myonuclear response observed with carbohydrate-protein seem to indicate that protein supplementation may have minimized the necessity for satellite cell involvement, thereby suggesting that protein may benefit skeletal muscle during periods of heavy training. PMID:27899900

Space Shuttle Main Engine Low Pressure Oxidizer Turbo-Pump Inducer Dynamic Environment Characterization through Water Model and Hot-Fire Testing

NASA Technical Reports Server (NTRS)

Arellano, Patrick; Patton, Marc; Schwartz, Alan; Stanton, David

2006-01-01

The Low Pressure Oxidizer Turbopump (LPOTP) inducer on the Block II configuration Space Shuttle Main Engine (SSME) experienced blade leading edge ripples during hot firing. This undesirable condition led to a minor redesign of the inducer blades. This resulted in the need to evaluate the performance and the dynamic environment of the redesign, relative to the current configuration, as part of the design acceptance process. Sub-scale water model tests of the two inducer configurations were performed, with emphasis on the dynamic environment due to cavitation induced vibrations. Water model tests were performed over a wide range of inlet flow coefficient and pressure conditions, representative of the scaled operating envelope of the Block II SSME, both in flight and in ground hot-fire tests, including all power levels. The water test hardware, facility set-up, type and placement of instrumentation, the scope of the test program, specific test objectives, data evaluation process and water test results that characterize and compare the two SSME LPOTP inducers are discussed. In addition, dynamic characteristics of the two water models were compared to hot fire data from specially instrumented ground tests. In general, good agreement between the water model and hot fire data was found, which confirms the value of water model testing for dynamic characterization of rocket engine turbomachinery.

Autophagy contributes to apoptosis in A20 and EL4 lymphoma cells treated with fluvastatin.

PubMed

Qi, Xu-Feng; Kim, Dong-Heui; Lee, Kyu-Jae; Kim, Cheol-Su; Song, Soon-Bong; Cai, Dong-Qing; Kim, Soo-Ki

2013-11-08

Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. However, the relationship between apoptosis and autophagy in lymphoma cells exposed to statins remains unclear. The objective of this study was to elucidate the potential involvement of autophagy in fluvastatin-induced cell death of lymphoma cells. We found that fluvastatin treatment enhanced the activation of pro-apoptotic members such as caspase-3 and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells. The process was accompanied by increases in numbers of annexin V alone or annexin V/PI double positive cells. Furthermore, both autophagosomes and increases in levels of LC3-II were also observed in fluvastatin-treated lymphoma cells. However, apoptosis in fluvastatin-treated lymphoma cells could be blocked by the addition of 3-methyladenine (3-MA), the specific inhibitor of autophagy. Fluvastatin-induced activation of caspase-3, DNA fragmentation, and activation of LC3-II were blocked by metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggest that autophagy contributes to fluvastatin-induced apoptosis in lymphoma cells, and that these regulating processes require inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.

Autophagy contributes to apoptosis in A20 and EL4 lymphoma cells treated with fluvastatin

PubMed Central

2013-01-01

Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. However, the relationship between apoptosis and autophagy in lymphoma cells exposed to statins remains unclear. The objective of this study was to elucidate the potential involvement of autophagy in fluvastatin-induced cell death of lymphoma cells. We found that fluvastatin treatment enhanced the activation of pro-apoptotic members such as caspase-3 and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells. The process was accompanied by increases in numbers of annexin V alone or annexin V/PI double positive cells. Furthermore, both autophagosomes and increases in levels of LC3-II were also observed in fluvastatin-treated lymphoma cells. However, apoptosis in fluvastatin-treated lymphoma cells could be blocked by the addition of 3-methyladenine (3-MA), the specific inhibitor of autophagy. Fluvastatin-induced activation of caspase-3, DNA fragmentation, and activation of LC3-II were blocked by metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggest that autophagy contributes to fluvastatin-induced apoptosis in lymphoma cells, and that these regulating processes require inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP. PMID:24209962

Modeling of DNA-Mediated Self-Assembly from Anisotropic Nanoparticles: A Molecular Dynamics Study

NASA Astrophysics Data System (ADS)

Millan, Jaime; Girard, Martin; Brodin, Jeffrey; O'Brien, Matt; Mirkin, Chad; Olvera de La Cruz, Monica

The programmable selectivity of DNA recognition constitutes an elegant scheme to self-assemble a rich variety of superlattices from versatile nanoscale building blocks, where the natural interactions between building blocks are traded by complementary DNA hybridization interactions. Recently, we introduced and validated a scale-accurate coarse-grained model for a molecular dynamics approach that captures the dynamic nature of DNA hybridization events and reproduces the experimentally-observed crystallization behavior of various mixtures of spherical DNA-modified nanoparticles. Here, we have extended this model to robustly reproduce the assembly of nanoparticles with the anisotropic shapes observed experimentally. In particular, we are interested in two different particle types: (i) regular shapes, namely the cubic and octahedral polyhedra shapes commonly observed in gold nanoparticles, and (ii) irregular shapes akin to those exhibited by enzymes. Anisotropy in shape can provide an analog to the atomic orbitals exhibited by conventional atomic crystals. We present results for the assembly of enzymes or anisotropic nanoparticles and the co-assembly of enzymes and nanoparticles.

Orbiter Atlantis (STS-110) Launch With New Block II Engines

NASA Technical Reports Server (NTRS)

2002-01-01

Powered by three newly-enhanced Space Shuttle Maine Engines (SSMEs), called the Block II Maine Engines, the Space Shuttle Orbiter Atlantis lifted off from the Kennedy Space Center launch pad on April 8, 2002 for the STS-110 mission. The Block II Main Engines incorporate an improved fuel pump featuring fewer welds, a stronger integral shaft/disk, and more robust bearings, making them safer and more reliable, and potentially increasing the number of flights between major overhauls. NASA continues to increase the reliability and safety of Shuttle flights through a series of enhancements to the SSME. The engines were modified in 1988 and 1995. Developed in the 1970s and managed by the Space Shuttle Projects Office at the Marshall Space Flight Center, the SSME is the world's most sophisticated reusable rocket engine. The new turbopump made by Pratt and Whitney of West Palm Beach, Florida, was tested at NASA's Stennis Space Center in Mississippi. Boeing Rocketdyne in Canoga Park, California, manufactures the SSME. This image was extracted from engineering motion picture footage taken by a tracking camera.

31 CFR 536.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 536.203 Section 536.203 Money and Finance: Treasury Regulations... NARCOTICS TRAFFICKING SANCTIONS REGULATIONS Prohibitions § 536.203 Holding of certain types of blocked...

31 CFR 536.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 536.203 Section 536.203 Money and Finance: Treasury Regulations... NARCOTICS TRAFFICKING SANCTIONS REGULATIONS Prohibitions § 536.203 Holding of certain types of blocked...

31 CFR 536.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 536.203 Section 536.203 Money and Finance: Treasury Regulations... NARCOTICS TRAFFICKING SANCTIONS REGULATIONS Prohibitions § 536.203 Holding of certain types of blocked...

31 CFR 536.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 536.203 Section 536.203 Money and Finance: Treasury Regulations... NARCOTICS TRAFFICKING SANCTIONS REGULATIONS Prohibitions § 536.203 Holding of certain types of blocked...

31 CFR 536.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 536.203 Section 536.203 Money and Finance: Treasury Regulations... NARCOTICS TRAFFICKING SANCTIONS REGULATIONS Prohibitions § 536.203 Holding of certain types of blocked...

[Effect of spatial location on the generality of block-wise conflict adaptation between different types of scripts].

PubMed

Watanabe, Yurina; Yoshizaki, Kazuhito

2014-10-01

This study aimed to investigate the generality of conflict adaptation associated with block-wise conflict frequency between two types of stimulus scripts (Kanji and Hiragana). To this end, we examined whether the modulation of the compatibility effect with one type of script depending on block-wise conflict frequency (75% versus 25% generalized to the other type of script whose block-wise conflict frequency was kept constant (50%), using the Spatial Stroop task. In Experiment 1, 16 participants were required to identify the target orientation (up or down) presented in the upper or lower visual-field. The results showed that block-wise conflict adaptation with one type of stimulus script generalized to the other. The procedure in Experiment 2 was the same as that in Experiment 1, except that the presentation location differed between the two types of stimulus scripts. We did not find a generalization from one script to the other. These results suggest that presentation location is a critical factor contributing to the generality of block-wise conflict adaptation.

Advanced Residual Strength Degradation Rate Modeling for Advanced Composite Structures. Volume II. Tasks II and III.

DTIC Science & Technology

1981-07-01

ADVANCED COMPOSITE STRUCTURES VOLUME II - TASKS Ix AND III K. N. Lauraitis Tl J. T. Ryder ?l4 D. E. Pettit ~ Lockheed-California Company S Burbank...Strength Degradation Rate Final Report Modeling for Advanced Composite Structures 1 July 1979 to 29 May 1981 Vol II - Task II and III S. PERFORMIN ONG...identify by block namber) composites , graphite/epoxy, impact damage, damaged holes, fatigue, damage propagation, residual strength, NDI 20. ABSTRACT

47 CFR 54.310 - Connect America Fund for Price Cap Territories-Phase II

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund for Price Cap Territories... Connect America Fund for Price Cap Territories—Phase II (a) Geographic areas eligible for support. Connect America Phase II support may be made available for census blocks or other areas identified as eligible by...

Organic photosensitive cells having a reciprocal-carrier exciton blocking layer

DOEpatents

Rand, Barry P [Princeton, NJ; Forrest, Stephen R [Princeton, NJ; Thompson, Mark E [Anaheim Hills, CA

2007-06-12

A photosensitive cell includes an anode and a cathode; a donor-type organic material and an acceptor-type organic material forming a donor-acceptor junction connected between the anode and the cathode; and an exciton blocking layer connected between the acceptor-type organic material of the donor-acceptor junction and the cathode, the blocking layer consisting essentially of a material that has a hole mobility of at least 10.sup.-7 cm.sup.2/V-sec or higher, where a HOMO of the blocking layer is higher than or equal to a HOMO of the acceptor-type material.

Frequency stability of on-orbit GPS Block-I and Block-II Navstar clocks

NASA Astrophysics Data System (ADS)

McCaskill, Thomas B.; Reid, Wilson G.; Buisson, James A.

On-orbit analysis of the Global Positioning System (GPS) Block-I and Block-II Navstar clocks has been performed by the Naval Research Laboratory using a multi-year database. The Navstar clock phase-offset measurements were computed from pseudorange measurements made by the five GPS monitor sites and from the U.S. Naval Observatory precise-time site using single or dual frequency GPS receivers. Orbital data was obtained from the Navstar broadcast ephemeris and from the best-fit, postprocessed orbital ephemerides supplied by the Naval Surface Weapons Center or by the Defense Mapping Agency. Clock performance in the time domain is characterized using frequency-stability profiles with sample times that vary from 1 to 100 days. Composite plots of Navstar frequency stability and time-prediction uncertainty are included as a summary of clock analysis results. The analysis includes plots of the clock phase offset and frequency offset histories with the eclipse seasons superimposed on selected plots to demonstrate the temperature sensitivity of one of the Block-I Navstar rubidium clocks. The potential impact on navigation and on transferring precise time of the degradation in the long-term frequency stability of the rubidium clocks is discussed.

Effects of oxyanions, natural organic matter, and bacterial cell numbers on the bioreduction of lepidocrocite ({gamma}-FeOOH) and the formation of secondary mineralization products.

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Loughlin, E. J.; Gorski, C. A.; Scherer, M. M.

Microbial reduction of Fe(III) oxides results in the production of Fe(II) and may lead to the subsequent formation of Fe(II)-bearing secondary mineralization products including magnetite, siderite, vivianite, chukanovite (ferrous hydroxy carbonate (FHC)), and green rust; however, the factors controlling the formation of specific Fe(II) phases are often not well-defined. This study examined effects of (i) a range of inorganic oxyanions (arsenate, borate, molybdate, phosphate, silicate, and tungstate), (ii) natural organic matter (citrate, oxalate, microbial extracellular polymeric substances [EPS], and humic substances), and (iii) the type and number of dissimilatory iron-reducing bacteria on the bioreduction of lepidocrocite and formation of Fe(II)-bearingmore » secondary mineralization products. The bioreduction kinetics clustered into two distinct Fe(II) production profiles. 'Fast' Fe(II) production kinetics [19-24 mM Fe(II) d-1] were accompanied by formation of magnetite and FHC in the unamended control and in systems amended with borate, oxalate, gellan EPS, or Pony Lake fulvic acid or having 'low' cell numbers. Systems amended with arsenate, citrate, molybdate, phosphate, silicate, tungstate, EPS from Shewanella putrefaciens CN32, or humic substances derived from terrestrial plant material or with 'high' cell numbers exhibited comparatively slow Fe(II) production kinetics [1.8-4.0 mM Fe(II) d-1] and the formation of green rust. The results are consistent with a conceptual model whereby competitive sorption of more strongly bound anions blocks access of bacterial cells and reduced electron-shuttling compounds to sites on the iron oxide surface, thereby limiting the rate of bioreduction.« less

Ultrasound-guided transversus abdominis plane block in patients undergoing open inguinal hernia repair: 0.125% bupivacaine provides similar analgesic effect compared to 0.25% bupivacaine.

PubMed

Erdoğan Arı, Dilek; Yıldırım Ar, Arzu; Karadoğan, Firdevs; Özcabı, Yetkin; Koçoğlu, Ayşegül; Kılıç, Fatih; Akgün, Fatma Nur

2016-02-01

To evaluate the effectiveness of 0.125% bupivacaine compared to 0.25% bupivacaine for ultrasound-guided transversus abdominis plane (TAP) block in patients undergoing open inguinal hernia repair. Randomized, double-blind study. Educational and research hospital. Forty adult patients of American Society of Anesthesiologists physical status I-III undergoing elective primary unilateral open inguinal hernia repair under spinal anesthesia. Patients in group I received 20 mL of 0.25% bupivacaine, whereas patients in group II received 20 mL of 0.125% bupivacaine for TAP block at the end of the surgery. Pain intensity was assessed at rest and during coughing using 10-cm visual analog scale score at 5, 15, 30, and 45 minutes and 1, 2, 4, 6, 12, and 24 hours after TAP block. Morphine consumption and time to first morphine requirement were recorded. Visual analog scale scores at rest and during coughing were not significantly different between groups at all time points measured. Twenty-four hours of morphine consumption (7.72±7.33 mg in group I and 6.06±5.20 mg in group II; P=.437) and time to first morphine requirement (182.35±125.16 minutes in group I and 143.21±87.28 minutes in group II; P=.332) were not different between groups. 0.125% Bupivacaine provides similar analgesic effect compared to 0.25% bupivacaine for ultrasound-guided TAP block in patients undergoing open inguinal hernia repair. Copyright © 2016 Elsevier Inc. All rights reserved.

Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinoma.

PubMed

Margulis, Alexander; Zhang, Weitian; Alt-Holland, Addy; Pawagi, Sujata; Prabhu, Padmaja; Cao, Jian; Zucker, Stanley; Pfeiffer, Laurence; Garfield, Jacqueline; Fusenig, Norbert E; Garlick, Jonathan A

2006-02-15

The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd-Ecad). Three-dimensional human tissue constructs harboring either H-2Kd-Ecad-expressing or control II-4 cells (pBabe, H-2Kd-EcadDeltaC25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd-Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 gamma2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease.

Apollo experience report guidance and control systems: Primary guidance, navigation, and control system development

NASA Technical Reports Server (NTRS)

Holley, M. D.; Swingle, W. L.; Bachman, S. L.; Leblanc, C. J.; Howard, H. T.; Biggs, H. M.

1976-01-01

The primary guidance, navigation, and control systems for both the lunar module and the command module are described. Development of the Apollo primary guidance systems is traced from adaptation of the Polaris Mark II system through evolution from Block I to Block II configurations; the discussion includes design concepts used, test and qualification programs performed, and major problems encountered. The major subsystems (inertial, computer, and optical) are covered. Separate sections on the inertial components (gyroscopes and accelerometers) are presented because these components represent a major contribution to the success of the primary guidance, navigation, and control system.

Commencement Bay Studies Phase II, Environmental Impacts Assessment.

DTIC Science & Technology

1983-10-01

Approved for public release, distribution unlimited. 17. DISTRIBUTION STATEMENT (of the absirct entered In Block 20. If dlfforent from Report) IS...Matrix (Appendix D). 19. KEY WORDS (Continue n reveres side itnecsewy and identify by block number) Salmonids Wetlands Aesthetics City of Tacoma Marine...Water Quality Land and Water Use Port of Tacoma t AEINACr (Cm as ,.verem ebb N c evesey a - fdoswif by block n mbs) ames and Moore assessed the

Defect-Property Relationships in Composite Materials. Part II.

DTIC Science & Technology

1977-06-01

requires the use of a delay block since the composite specimens are so thin that returning echoes overlap one another on the screen of the cathode -ray...tube and can not be individually distinguished. The delay block, when placed on the opposite Oide of the specimen from the transducer, increases the

14 CFR 23.1325 - Static pressure system.

Code of Federal Regulations, 2010 CFR

2010-01-01

...— (i) Positive drainage of moisture is provided; (ii) Chafing of the tubing, and excessive distortion... source must be designed so that— (1) When either source is selected, the other is blocked off; and (2) Both sources cannot be blocked off simultaneously. (d) For unpressurized airplanes, paragraph (c)(1) of...

2 CFR 200.101 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... authorized under the Child Care and Development Block Grant Act of 1990, as amended: (i) Child Care and Development Block Grant (42 U.S.C. 9858) (ii) Child Care Mandatory and Matching Funds of the Child Care and... programs: (i) Special Supplemental Nutrition Program for Women, Infants and Children (section 17 of the...

Module performance and failure analysis area: Flat-plate solar array project

NASA Technical Reports Server (NTRS)

Tornstrom, E.

1984-01-01

A redesign of the initial (Group I) Mobile Solar Block V module was done and documented. Manufacturing experience and accelerated test data from Group I formed the basis for the redesign. Ten Block V Group II modules were submitted for evaluation and the results are presented.

31 CFR 595.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TERRORISM SANCTIONS REGULATIONS Prohibitions § 595.203 Holding of certain types of blocked property in... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 595.203 Section 595.203 Money and Finance: Treasury Regulations...

31 CFR 575.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... IRAQI SANCTIONS REGULATIONS Prohibitions § 575.203 Holding of certain types of blocked property in... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 575.203 Section 575.203 Money and Finance: Treasury Regulations...

31 CFR 595.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TERRORISM SANCTIONS REGULATIONS Prohibitions § 595.203 Holding of certain types of blocked property in... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 595.203 Section 595.203 Money and Finance: Treasury Regulations...

31 CFR 595.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TERRORISM SANCTIONS REGULATIONS Prohibitions § 595.203 Holding of certain types of blocked property in... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 595.203 Section 595.203 Money and Finance: Treasury Regulations...

31 CFR 595.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... TERRORISM SANCTIONS REGULATIONS Prohibitions § 595.203 Holding of certain types of blocked property in... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 595.203 Section 595.203 Money and Finance: Treasury Regulations...

31 CFR 595.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... TERRORISM SANCTIONS REGULATIONS Prohibitions § 595.203 Holding of certain types of blocked property in... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 595.203 Section 595.203 Money and Finance: Treasury Regulations...

Roles of type II thioesterases and their application for secondary metabolite yield improvement.

PubMed

Kotowska, Magdalena; Pawlik, Krzysztof

2014-09-01

A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from simple substrates, such as carboxylic acids and amino acids. Modular PKSs and NRPSs, often referred to as megasynthases, have brought about a special interest due to the colinearity between enzymatic domains in the proteins working as an "assembly line" and the chain elongation and modification steps. Extensive efforts toward modified compound biosynthesis by changing organization of PKS and NRPS domains in a combinatorial manner laid good grounds for rational design of new structures and their controllable biosynthesis as proposed by the synthetic biology approach. Despite undeniable progress made in this field, the yield of such "unnatural" natural products is often not satisfactory. Here, we focus on type II thioesterases (TEIIs)--discrete hydrolytic enzymes often encoded within PKS and NRPS gene clusters which can be used to enhance product yield. We review diverse roles of TEIIs (removal of aberrant residues blocking the megasynthase, participation in substrate selection, intermediate, and product release) and discuss their application in new biosynthetic systems utilizing PKS and NRPS parts.

The second Lilly Prize Lecture, University of Newcastle, July 1977. beta-Adrenergic receptor blockade in hypertension, past, present and future.

PubMed Central

Prichard, B N

1978-01-01

All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs have been reported which also possess alpha-adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta-adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta-adrenoceptor blocking drugs. The non-selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I-IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta-adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub-divided into groups I-IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta-adrenergic receptor blocking drugs which in addition have alpha- adrenergic receptor blocking properties (Division III). PMID:26370

Clinical and electrophysiological characteristics of patients with paroxysmal intra-His block with narrow QRS complexes.

PubMed

Ragupathi, Loheetha; Johnson, Drew; Greenspon, Arnold; Frisch, Daniel; Ho, Reginald T; Pavri, Behzad B

2018-04-18

Atrioventricular (AV) block is usually due to infranodal disease and associated with a wide QRS complex; such patients often progress to complete AV block and pacemaker dependency. Uncommonly, infranodal AV block can occur within the His bundle with a narrow QRS complex. The aims of this study were to define clinical/echocardiographic characteristics of patients with AV block within the His bundle and report progression to pacemaker dependency. We retrospectively identified patients with narrow QRS complexes and documented intra-His delay or block at electrophysiology study (group A) or with electrocardiogram-documented Mobitz II AV block/paroxysmal AV block (group B). Clinical, electrophysiological, and echocardiographic variables at presentation and pacemaker parameters at the last follow-up visit were evaluated. Twenty-seven patients (19 women) were identified (mean age 64 ± 13 years; range, 38-85 years). Four patients who had <1 month of follow-up were excluded. There were 12 patients in group A and 11 in group B; 21 of 23 presented with syncope/presyncope. All patients received pacemakers: 8 single chamber and 15 dual chamber. After a median follow-up of 6.4 years, the median percentage of ventricular pacing was 1% (interquartile range 0%-4.66%). One patient developed true pacemaker dependency. Aortic and/or mitral annular calcification was present in 13 of 22 patients with available echocardiograms. Patients who present with syncope and narrow QRS complexes with intra-His delay or Mobitz II paroxysmal AV block with narrow QRS complexes rarely progress to pacemaker dependency and require infrequent pacing. This entity is more common in women, with a higher prevalence of aortic and/or mitral annular calcification. If confirmed by additional studies, single-chamber pacemaker may be sufficient. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Human induced pluripotent stem cell‐derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block

PubMed Central

Paci, M; Hyttinen, J; Rodriguez, B

2015-01-01

Background and Purpose Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) and in silico human adult ventricular cardiomyocyte (hAdultV‐CM) models. Their combination was recently proposed as a potential replacement for the present hERG‐based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC‐CM and hAdultV‐CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. Experimental Approach In silico AP models of ventricular‐like and atrial‐like hiPSC‐CMs and hAdultV‐CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. Key Results Qualitatively, hiPSC‐CM and hAdultV‐CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC‐CMs were more sensitive to block of (i) L‐type Ca2+ currents due to the overexpression of the Na+/Ca2+ exchanger (leading to shorter APs) and (ii) the inward rectifier K+ current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). Conclusions and Implications In silico hiPSC‐CMs and hAdultV‐CMs exhibit a similar response to selective current blocks. However, overall hiPSC‐CMs show greater sensitivity to block, which may facilitate in vitro identification of drug‐induced effects. Extrapolation of drug effects from hiPSC‐CM to hAdultV‐CM and pro‐arrhythmic risk assessment can be facilitated by in silico predictions using biophysically‐based computational models. PMID:26276951

Nonalcoholic fatty liver disease is associated with an increased risk of heart block in hospitalized patients with type 2 diabetes mellitus.

PubMed

Mantovani, Alessandro; Rigolon, Riccardo; Pichiri, Isabella; Bonapace, Stefano; Morani, Giovanni; Zoppini, Giacomo; Bonora, Enzo; Targher, Giovanni

2017-01-01

Recent studies suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiac tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus. The aim of this study was to examine whether an association also exists between NAFLD and heart block. We have retrospectively evaluated a hospital-based cohort of 751 patients with type 2 diabetes discharged from our Division of Diabetes and Endocrinology during years 2007-2014. Standard electrocardiograms were performed on all patients. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced hepatic fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis markers. Overall, 524 (69.8%) patients had NAFLD and 202 (26.9%) had heart block (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block) on electrocardiograms. Patients with NAFLD had a remarkably higher prevalence of any persistent heart block than those without NAFLD (31.3% vs. 16.7%, p<0.001); this prevalence was particularly increased among those with higher FIB-4 score. NAFLD was associated with a threefold increased risk of prevalent heart block (adjusted-odds ratio 3.04, 95% CI 1.81-5.10), independently of age, sex, hypertension, prior ischemic heart disease, hemoglobin A1c, microvascular complication status, use of medications and other potentially confounding factors. In conclusion, this is the largest cross-sectional study to show that NAFLD and its severity are independently associated with an increased risk of prevalent heart block in hospitalized patients with type 2 diabetes.

Mechanism of triclosan toxicity: Mitochondrial dysfunction including complex II inhibition, superoxide release and uncoupling of oxidative phosphorylation.

PubMed

Teplova, Vera V; Belosludtsev, Konstantin N; Kruglov, Alexey G

2017-06-05

Triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol), a widely used antibacterial agent, exerts adverse effects on the organism of mammals. Recent research reviled that triclosan at low micromolar concentrations causes mitochondrial dysfunction in many cell types, but the mechanisms of its effect are not fully understood. Here we show that exposure to triclosan disrupted membrane potential, prevented the calcium uptake-driven high-amplitude mitochondrial swelling, stimulated the respiration in the presence of complex I substrates, and suppressed the ADP-stimulated respiration in the presence of complex II substrate, succinate. Triclosan directly inhibited complex II activity. Similar to the complex II inhibitor thenoyltrifluoroacetone, triclosan induced the oxidation of the cytochromes b566 and b562 and caused the release of mitochondrial superoxide. Opposite to thenoyltrifluoroacetone, triclosan increased superoxide release synergistically with myxothiazol but not with antimycin A, indicating different topology of superoxide-producing sites. We concluded that triclosan is unique by its capability of acting as both a protonophore and an unusual complex II inhibitor, which interferes with the mitochondrial respiration by blocking the electron transfer between ubiquinone at the Q d -binding site and heme b. Our data can provide an insight into the mechanisms of the carcinogenic effect of triclosan in the liver and other tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Mdm-2 binding and TAF(II)31 recruitment is regulated by hydrogen bond disruption between the p53 residues Thr18 and Asp21.

PubMed

Jabbur, James R; Tabor, Amy D; Cheng, Xiaodong; Wang, Hua; Uesugi, Motonari; Lozano, Guillermina; Zhang, Wei

2002-10-10

Analyses of five wild-type p53 containing cell lines revealed lineage specific differences in phosphorylation of Thr18 after treatment with ionizing (IR) or ultraviolet (UV) radiation. Importantly, Thr18 phosphorylation correlated with induction of the p53 downstream targets p21(Waf1/Cip1) (p21) and Mdm-2, suggesting a transactivation enhancing role. Thr18 phosphorylation has been shown to abolish side-chain hydrogen bonding between Thr18 and Asp21, an interaction necessary for stabilizing alpha-helical conformation within the transactivation domain. Mutagenesis-derived hydrogen bond disruption attenuated the interaction of p53 with the transactivation repressor Mdm-2 but had no direct effect on the interaction of p53 with the basal transcription factor TAF(II)31. However, prior incubation of p53 mutants with Mdm-2 modulated TAF(II)31 interaction with p53, suggesting Mdm-2 blocks the accessibility of p53 to TAF(II)31. Consistently, p53-null cells transfected with hydrogen bond disrupting p53 mutants demonstrated enhanced endogenous p21 expression, whereas p53/Mdm-2-double null cells exhibited no discernible differences in p21 expression. We conclude disruption of intramolecular hydrogen bonding between Thr18 and Asp21 enhances p53 transactivation by modulating Mdm-2 binding, facilitating TAF(II)31 recruitment.

Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

PubMed Central

Rodríguez-Peña, Ana B.; Fuentes-Calvo, Isabel; Docherty, Neil G.; Arévalo, Miguel; Grande, María T.; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M.

2014-01-01

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis. PMID:25101263

Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy.

PubMed

Rodríguez-Peña, Ana B; Fuentes-Calvo, Isabel; Docherty, Neil G; Arévalo, Miguel; Grande, María T; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M

2014-01-01

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

Experimental study on axial pedicled composite flap prefabrication with high density porous polyethylene implants: medporocutaneous flap.

PubMed

Kocman, A Emre; Kose, Aydan A; Karabagli, Yakup; Baycu, Cengiz; Cetin, Cengiz

2008-01-01

Composite flaps including soft tissues with bone or cartilage are widely used in reconstruction of three-dimensional defects, but have some disadvantages. Flap prefabrication with alloplastic implants is an alternative procedure. Axial pattern vascularised high density porous polyethylene (HDPP) implants are capable of sustaining skin grafts. The purpose of this study was to examine the vascularisation pattern of the skin island in a composite flap prefabrication model prepared with vascularised HDPP implants. Forty male Wistar rats divided into four groups were used. A 9.5 x 6 x 2 mm HDPP block was centered on the dissected saphenous pedicle and anchored under the abdominal skin in the experimental group I (n=10). In experimental group II (n=10) saphenous artery and vein were put between the skin and the implant. Thus, the structures were laid as skin, HDPP block, pedicle in experimental group I and skin, pedicle, HDPP block in experimental group II. HDPP block-implanted and pedicle-implanted only groups served as control groups I and II, respectively. Eight weeks after prefabrication, skin islands 1.5 x 5 cm in size incorporated with implants were elevated based on saphenous vessels in the experimental groups and skin islands only based on the pedicle in control group II. Skin islands of the same dimensions were raised as grafts in control group I. Nylon sheets were put under the flaps and grafts to prevent vascularisation from the recipient bed. Flap viability was assessed by measuring the surface area on the 7th day. Total necrosis developed in composite grafts of control group I. Flap survival was higher in experimental group II and control group II (45% and 46.8%) than in group I (29.28%). Histologic studies demonstrated fibrovascular ingrowth into the HDPP implants, except in control group I, with significant inflammatory response and necrosis. Vascularisation of skin and implants from the pedicle was seen also microangiographically. In conclusion, a composite flap prefabrication model including vascularised HDPP implant, skin and vascular carrier was developed. This new flap was termed a 'medporocutaneous flap'.

Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice.

PubMed

Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

2014-05-16

Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Regulation of Primary Afferent Input to Spinal Cord by Muscarinic Receptor Subtypes Delineated Using Knockout Mice*

PubMed Central

Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

2014-01-01

Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. PMID:24695732

Job Aids: Descriptive Authoring Flowcharts for Phase II--DESIGN of the Instructional Systems Development Model.

ERIC Educational Resources Information Center

Schulz, Russel E.; Farrell, Jean R.

This resource guide for the use of job aids ("how-to-do-it" guidance) for activities identified in the second phase of the Instructional Systems Development Model (ISD) contains an introduction to the use of job aids, as well as descriptive authoring flowcharts for Blocks II.1 through II.4. The introduction includes definitions;…

Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis.

PubMed

Li, Huiyan; Peng, Xuan; Wang, Yating; Cao, Shirong; Xiong, Liping; Fan, Jinjin; Wang, Yihan; Zhuang, Shougang; Yu, Xueqing; Mao, Haiping

2016-09-01

Macroautophagy/autophagy protects against cellular stress. Renal sublethal injury-triggered tubular epithelial cell cycle arrest at G2/M is associated with interstitial fibrosis. However, the role of autophagy in renal fibrosis is elusive. Here, we hypothesized that autophagy activity in tubular epithelial cells is pivotal for inhibition of cell cycle G2/M arrest and subsequent fibrogenic response. In both renal epithelial cells stimulated by angiotensin II (AGT II) and the murine kidney after unilateral ureteral obstruction (UUO), we observed that occurrence of autophagy preceded increased production of COL1 (collagen, type I). Pharmacological enhancement of autophagy by rapamycin suppressed COL1 accumulation and renal fibrosis. In contrast, genetic ablation of autophagy by proximal tubular epithelial cell-specific deletion of Atg5, with reduction of the LC3-II protein level and degradation of SQSTM1/p62, showed marked cell cycle arrest at the G2/M phase, robust COL1 deposition, and severe interstitial fibrosis in a UUO model, as compared with wild-type mice. In vitro, AGT II exposure triggered autophagy preferentially in the G1/S phase, and increased COL1 expression in the G2/M phase in renal epithelial cells. Stimulation of Atg5-deficient primary proximal tubular cells with AGT II also resulted in elevated G2/M arrest and COL1 production. Pharmacological or genetic inhibition of autophagy increased AGT II-mediated G2/M arrest. Enhanced expression of ATG5, but not the autophagy-deficient ATG5 mutant K130R, rescued the G2/M arrest, suggesting the regulation of cell cycle progression by ATG5 is autophagy dependent. In conclusion, Atg5-mediated autophagy in proximal epithelial cells is a critical host-defense mechanism that prevents renal fibrosis by blocking G2/M arrest.

Tumor necrosis factor-α inhibits angiotensin II receptor type 1 expression in dorsal root ganglion neurons via β-catenin signaling.

PubMed

Yang, Y; Wu, H; Yan, J-Q; Song, Z-B; Guo, Q-L

2013-09-17

Both tumor necrosis factor (TNF)-α and the angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) axis play important roles in neuropathic pain and nociception. In the present study, we explored the interaction between the two systems by examining the mutual effects between TNF-α and the Ang II/AT1 receptor axis in dorsal root ganglion (DRG) neurons. Rat DRG neurons were treated with TNF-α in different concentrations for different lengths of time in the presence or absence of transcription inhibitor actinomycin D, TNF receptor 1 (TNFR1) inhibitor SPD304, β-catenin signaling inhibitor CCT031374, or different kinase inhibitors. TNF-α decreased the AT1 receptor mRNA level as well as the AT1a receptor promoter activity in a dose-dependent manner within 30 h, which led to dose-dependent inhibition of Ang II-binding AT1 receptor level on the cell membrane. Actinomycin D (1 mg/ml), SPD304 (50 μM), p38 mitogen-activated protein kinase (MAPK) inhibitor PD169316 (25 μM), and CCT031374 (50 μM) completely abolished the inhibitory effect of TNF-α on AT1 receptor expression. TNF-α dose-dependently increased soluble β-catenin and phosphorylated GSK-3β levels, which was blocked by SPD304 and PD169316. In DRG neurons treated with AT2 receptor agonist CGP421140, or Ang II with or without AT1 receptor antagonist losartan or AT2 receptor antagonist PD123319 for 30 h, we found that Ang II and Ang II+PD123319 significantly decreased TNF-α expression, whereas CPG421140 and Ang II+losartan increased TNF-α expression. In conclusion, we demonstrate that TNF-α inhibits AT1 receptor expression at the transcription level via TNFR1 in rat DRG neurons by increasing the soluble β-catenin level through the p38 MAPK/GSK-3β pathway. In addition, Ang II appears to inhibit and induce TNF-α expression via the AT1 receptor and the AT2 receptor in DRG neurons, respectively. This is the first evidence of crosstalk between TNF-α and the Ang II/AT receptor axis in DRG neurons. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Arginase Inhibition Suppresses Native Low-Density Lipoprotein-Stimulated Vascular Smooth Muscle Cell Proliferation by NADPH Oxidase Inactivation.

PubMed

Koo, Bon Hyeock; Yi, Bong Gu; Wang, Wi Kwang; Ko, In Young; Hoe, Kwang Lae; Kwon, Young Guen; Won, Moo Ho; Kim, Young Myeong; Lim, Hyun Kyo; Ryoo, Sungwoo

2018-05-01

Vascular smooth muscle cell (VSMC) proliferation induced by native low-density lipoprotein (nLDL) stimulation is dependent on superoxide production from activated NADPH oxidase. The present study aimed to investigate whether the novel arginase inhibitor limonin could suppress nLDL-induced VSMC proliferation and to examine related mechanisms. Isolated VSMCs from rat aortas were treated with nLDL, and cell proliferation was measured by WST-1 and BrdU assays. NADPH oxidase activation was evaluated by lucigenin-induced chemiluminescence, and phosphorylation of protein kinase C (PKC) βII and extracellular signal-regulated kinase (ERK) 1/2 was determined by western blot analysis. Mitochondrial reactive oxygen species (ROS) generation was assessed using MitoSOX-red, and intracellular L-arginine concentrations were determined by high-performance liquid chromatography (HPLC) in the presence or absence of limonin. Limonin inhibited arginase I and II activity in the uncompetitive mode, and prevented nLDL-induced VSMC proliferation in a p21Waf1/Cip1-dependent manner without affecting arginase protein levels. Limonin blocked PKCβII phosphorylation, but not ERK1/2 phosphorylation, and translocation of p47phox to the membrane was decreased, as was superoxide production in nLDL-stimulated VSMCs. Moreover, mitochondrial ROS generation was increased by nLDL stimulation and blocked by preincubation with limonin. Mitochondrial ROS production was responsible for the phosphorylation of PKCβII. HPLC analysis showed that arginase inhibition with limonin increases intracellular L-arginine concentrations, but decreases polyamine concentrations. L-Arginine treatment prevented PKCβII phosphorylation without affecting ERK1/2 phosphorylation. Increased L-arginine levels following limonin-dependent arginase inhibition prohibited NADPH oxidase activation in a PKCβII-dependent manner, and blocked nLDL-stimulated VSMC proliferation. © Copyright: Yonsei University College of Medicine 2018.

Arginase Inhibition Suppresses Native Low-Density Lipoprotein-Stimulated Vascular Smooth Muscle Cell Proliferation by NADPH Oxidase Inactivation

PubMed Central

Wang, Wi-Kwang; Ko, In-Young; Hoe, Kwang-Lae; Kwon, Young-Guen; Won, Moo-Ho; Kim, Young-Myeong

2018-01-01

Purpose Vascular smooth muscle cell (VSMC) proliferation induced by native low-density lipoprotein (nLDL) stimulation is dependent on superoxide production from activated NADPH oxidase. The present study aimed to investigate whether the novel arginase inhibitor limonin could suppress nLDL-induced VSMC proliferation and to examine related mechanisms. Materials and Methods Isolated VSMCs from rat aortas were treated with nLDL, and cell proliferation was measured by WST-1 and BrdU assays. NADPH oxidase activation was evaluated by lucigenin-induced chemiluminescence, and phosphorylation of protein kinase C (PKC) βII and extracellular signal-regulated kinase (ERK) 1/2 was determined by western blot analysis. Mitochondrial reactive oxygen species (ROS) generation was assessed using MitoSOX-red, and intracellular L-arginine concentrations were determined by high-performance liquid chromatography (HPLC) in the presence or absence of limonin. Results Limonin inhibited arginase I and II activity in the uncompetitive mode, and prevented nLDL-induced VSMC proliferation in a p21Waf1/Cip1-dependent manner without affecting arginase protein levels. Limonin blocked PKCβII phosphorylation, but not ERK1/2 phosphorylation, and translocation of p47phox to the membrane was decreased, as was superoxide production in nLDL-stimulated VSMCs. Moreover, mitochondrial ROS generation was increased by nLDL stimulation and blocked by preincubation with limonin. Mitochondrial ROS production was responsible for the phosphorylation of PKCβII. HPLC analysis showed that arginase inhibition with limonin increases intracellular L-arginine concentrations, but decreases polyamine concentrations. L-Arginine treatment prevented PKCβII phosphorylation without affecting ERK1/2 phosphorylation. Conclusion Increased L-arginine levels following limonin-dependent arginase inhibition prohibited NADPH oxidase activation in a PKCβII-dependent manner, and blocked nLDL-stimulated VSMC proliferation. PMID:29611398

Angiotensin II potentiates zinc-induced cortical neuronal death by acting on angiotensin II type 2 receptor.

PubMed

Park, Mi-Ha; Kim, Ha Na; Lim, Joon Seo; Ahn, Jae-Sung; Koh, Jae-Young

2013-12-01

The angiotensin system has several non-vascular functions in the central nervous system. For instance, inhibition of the brain angiotensin system results in a reduction in neuronal death following acute brain injury such as ischemia and intracerebral hemorrhage, even under conditions of constant blood pressure. Since endogenous zinc has been implicated as a key mediator of ischemic neuronal death, we investigated the possibility that the angiotensin system affects the outcome of zinc-triggered neuronal death in cortical cell cultures. Exposure of cortical cultures containing neurons and astrocytes to 300 μM zinc for 15 min induced submaximal death in both types of cells. Interestingly, addition of angiotensin II significantly enhanced the zinc-triggered neuronal death, while leaving astrocytic cell death relatively unchanged. Both type 1 and 2 angiotensin II receptors (AT1R and AT2R, respectively) were expressed in neurons as well as astrocytes. Zinc neurotoxicity was substantially attenuated by PD123319, a specific inhibitor of AT2R, and augmented by CGP42112, a selective activator of AT2R, indicating a critical role for this receptor subtype in the augmentation of neuronal cell death.Because zinc toxicity occurs largely through oxidative stress, the levels of superoxides in zinc-treated neurons were assessed by DCF fluorescence microscopy. Combined treatment with zinc and angiotensin II substantially increased the levels of superoxides in neurons compared to those induced by zinc alone. This increase in oxidative stress by angiotensin II was completely blocked by the addition of PD123319. Finally, since zinc-induced oxidative stress may be caused by induction and/or activation of NADPH oxidase, the activation status of Rac and the level of the NADPH oxidase subunit p67phox were measured. Angiotensin II markedly increased Rac activity and the levels of p67phox in zinc-treated neurons and astrocytes in a PD123319-dependent manner. The present study shows that the angiotensin system, especially that involving AT2R, may have an oxidative injury-potentiating effect via augmentation of the activity of NADPH oxidase. Hence, blockade of angiotensin signaling cascades in the brain may prove useful in protecting against the oxidative neuronal death that is likely to occur in acute brain injury.

Epileptogenesis causes an N-methyl-d-aspartate receptor/Ca2+-dependent decrease in Ca2+/calmodulin-dependent protein kinase II activity in a hippocampal neuronal culture model of spontaneous recurrent epileptiform discharges.

PubMed

Blair, Robert E; Sombati, Sompong; Churn, Severn B; Delorenzo, Robert J

2008-06-24

Alterations in the function of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) have been observed in both in vivo and in vitro models of epileptogenesis; however the molecular mechanism mediating the effects of epileptogenesis on CaM kinase II has not been elucidated. This study was initiated to evaluate the molecular pathways involved in causing the long-lasting decrease in CaM kinase II activity in the hippocampal neuronal culture model of low Mg2+-induced spontaneous recurrent epileptiform discharges (SREDs). We show here that the decrease in CaM kinase II activity associated with SREDs in hippocampal cultures involves a Ca2+/N-methyl-d-aspartate (NMDA) receptor-dependent mechanism. Low Mg2+-induced SREDs result in a significant decrease in Ca2+/calmodulin-dependent substrate phosphorylation of the synthetic peptide autocamtide-2. Reduction of extracellular Ca2+ levels (0.2 mM in treatment solution) or the addition of dl-2-amino-5-phosphonovaleric acid (APV) 25 microM blocked the low Mg2+-induced decrease in CaM kinase II-dependent substrate phosphorylation. Antagonists of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid receptor or L-type voltage sensitive Ca2+ channel had no effect on the low Mg2+-induced decrease in CaM kinase II-dependent substrate phosphorylation. The results of this study demonstrate that the decrease in CaM kinase II activity associated with this model of epileptogenesis involves a selective Ca2+/NMDA receptor-dependent mechanism and may contribute to the production and maintenance of SREDs in this model.

Epileptogenesis causes an N-methyl-d-aspartate receptor/Ca2+-dependent decrease in Ca2+/calmodulin-dependent protein kinase II activity in a hippocampal neuronal culture model of spontaneous recurrent epileptiform discharges

PubMed Central

Blair, Robert E.; Sombati, Sompong; Churn, Severn B.; DeLorenzo, Robert J.

2008-01-01

Alterations in the function of Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) have been observed in both in vivo and in vitro models of epileptogenesis; however the molecular mechanism mediating the effects of epileptogenesis on CaM Kinase II have not been elucidated. This study was initiated to evaluate the molecular pathways involved in causing the long lasting decrease in CaM Kinase II activity in the hippocampal neuronal culture model of low Mg2+ induced spontaneous recurrent epileptiform discharges (SREDs). We show here that the decrease in CaM kinase II activity associated with SREDs in hippocampal cultures involves a Ca2+/N-methyl-d-aspartate (NMDA) receptor-dependent mechanism. Low Mg2+ induced SREDs results in a significant decrease in Ca2+/calmodulin-dependent substrate phosphorylation of the synthetic peptide autocamtide-2. Reduction of extracellular Ca2+ levels (0.2 mM in treatment solution) or the addition of DL-2-amino-5-phosphonovaleric acid (APV) 25 µM blocked the low Mg2+ induced decrease in CaM kinase II-dependent substrate phosphorylation. Antagonists of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid receptor or L-type voltage sensitive Ca2+ channel had no effect on the low Mg2+ induced decrease in CaM kinase II-dependent substrate phosphorylation. The results of this study demonstrate that the decrease in CaM kinase II activity associated with this model of epileptogenesis involves a selective Ca2+/NMDA receptor-dependent mechanism and may contribute to the production and maintenance of SREDs in this model. PMID:18495112

Assessment of pulse oximeter perfusion index in pediatric caudal block under basal ketamine anesthesia.

PubMed

Xu, Zifeng; Zhang, Jianhai; Shen, Hao; Zheng, Jijian

2013-01-01

Whether pulse oximeter perfusion index (PI) may be applied to detect the onset of caudal block in pediatric patients under ketamine intravenous basal anesthesia is investigated. 40 ASA I, 2-8-year-old boys scheduled for elective circumcision surgery were randomized into two groups. Group I: 20 patients were anesthetized by 2 mg·kg(-1) ketamine intravenous injection (IV) followed by caudal block using 1 mL·kg(-1) lidocaine (1%); Group II: 20 patients were anesthetized by 2 mg·kg(-1) ketamine IV only. PI on the toe in Group II decreased by 33 ± 12%, 71 ± 9% and 65 ± 8% at 1 min, 15 min, and 30 min after ketamine injection. The maximum increase in MAP and HR after ketamine IV was 11 ± 6% at 3 min and 10 ± 6% at 2 min. Compared to the PI value before caudal injection of lidocaine, PI in Group I increased by 363 ± 318% and 778 ± 578% at 5 min and 20 min after caudal block, while no significant changes in MAP and HR were found compared to the baseline before caudal block. Thus, PI provides an earlier, more objective, and more sensitive indicator to assess the early onset of caudal block under basal ketamine anesthesia.

Masonry Specialist I & II, 3-19. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

These military-developed curriculum materials consist of a course description, plan of instruction, study guides, and workbooks for use in training masonry specialists. Covered in the course blocks are an introduction to masonry and rigid concrete structures. The introduction to masonry, course block I, deals with safety, mathematics and…

76 FR 29143 - Blocking Property of Senior Officials of the Government of Syria

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... Order 13573 of May 18, 2011 Blocking Property of Senior Officials of the Government of Syria By the... of Syria's continuing escalation of violence against the people of Syria--including through attacks... be a senior official of the Government of Syria; (ii) to be an agency or instrumentality of the...

Human tRNA genes function as chromatin insulators

PubMed Central

Raab, Jesse R; Chiu, Jonathan; Zhu, Jingchun; Katzman, Sol; Kurukuti, Sreenivasulu; Wade, Paul A; Haussler, David; Kamakaka, Rohinton T

2012-01-01

Insulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs are repetitive sequences dispersed throughout the human genome and we now show that some of these tDNAs can function as insulators in human cells. Using computational methods, we identified putative human tDNA insulators. Using silencer blocking, transgene protection and repressor blocking assays we show that some of these tDNA-containing fragments can function as barrier insulators in human cells. We find that these elements also have the ability to block enhancers from activating RNA pol II transcribed promoters. Characterization of a putative tDNA insulator in human cells reveals that the site possesses chromatin signatures similar to those observed at other better-characterized eukaryotic insulators. Enhanced 4C analysis demonstrates that the tDNA insulator makes long-range chromatin contacts with other tDNAs and ETC sites but not with intervening or flanking RNA pol II transcribed genes. PMID:22085927

Block algebra in two-component BKP and D type Drinfeld-Sokolov hierarchies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Chuanzhong, E-mail: lichuanzhong@nbu.edu.cn; He, Jingsong, E-mail: hejingsong@nbu.edu.cn

We construct generalized additional symmetries of a two-component BKP hierarchy defined by two pseudo-differential Lax operators. These additional symmetry flows form a Block type algebra with some modified (or additional) terms because of a B type reduction condition of this integrable hierarchy. Further we show that the D type Drinfeld-Sokolov hierarchy, which is a reduction of the two-component BKP hierarchy, possess a complete Block type additional symmetry algebra. That D type Drinfeld-Sokolov hierarchy has a similar algebraic structure as the bigraded Toda hierarchy which is a differential-discrete integrable system.

Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice1

PubMed Central

Kojima, Fumiaki; Kapoor, Mohit; Yang, Lihua; Fleishaker, Erica L.; Ward, Martin R.; Monrad, Seetha U.; Kottangada, Ponnappa C.; Pace, Charles Q.; Clark, James A.; Woodward, Jerold G.; Crofford, Leslie J.

2008-01-01

Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH2 to PGE2. The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen (CII), including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. PMID:18523303

Granulocyte macrophage-colony stimulating factor and interleukin-3 increase expression of type II tumour necrosis factor receptor, increasing susceptibility to tumour necrosis factor-induced apoptosis. Control of leukaemia cell life/death switching.

PubMed

Rae, C; MacEwan, D J

2004-12-01

Tumour necrosis factor (TNF) induces apoptosis in a range of cell types via its two receptors, TNFR1 and TNFR2. Here, we demonstrate that proliferation and TNFR2 expression was increased in human leukaemic TF-1 cells by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), with TNFR1 expression unaffected. Consequently, they switch from a proliferative to a TNF-induced apoptotic phenotype. Raised TNFR2 expression and susceptibility to TNF-induced apoptosis was not a general effect of proliferation as IL-1beta and IFN-gamma both proliferated TF-1 cells with no effect on TNFR expression or apoptosis. Although raised TNFR2 expression correlated with the apoptotic phenotype, stimulation of apoptosis in GM-CSF-pretreated cells was mediated by TNFR1, with stimulation of TNFR2 alone insufficient to initiate cell death. However, TNFR2 did play a role in apoptotic and proliferative responses as they were blocked by the presence of an antagonistic TNFR2 antibody. Additionally, coincubation with cycloheximide blocked the mitotic effects of GM-CSF or IL-3, allowing only the apoptotic responses of TNF to persist. TNF life/death was also observed in K562, but not MOLT-4 and HL-60 human leukaemic cell types. These findings show a cooperative role of TNFR2 in the TNF life/death switching phenomenon.

A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas.

PubMed

Sun, Yu; Alberta, John A; Pilarz, Catherine; Calligaris, David; Chadwick, Emily J; Ramkissoon, Shakti H; Ramkissoon, Lori A; Garcia, Veronica Matia; Mazzola, Emanuele; Goumnerova, Liliana; Kane, Michael; Yao, Zhan; Kieran, Mark W; Ligon, Keith L; Hahn, William C; Garraway, Levi A; Rosen, Neal; Gray, Nathanael S; Agar, Nathalie Y; Buhrlage, Sara J; Segal, Rosalind A; Stiles, Charles D

2017-06-01

Activating mutations or structural rearrangements in BRAF are identified in roughly 75% of all pediatric low-grade astrocytomas (PLGAs). However, first-generation RAF inhibitors approved for adult melanoma have poor blood-brain penetrance and are only effective on tumors that express the canonical BRAFV600E oncoprotein, which functions as a monomer. These drugs (type I antagonists that target the "DFG-in" conformation of the kinase) fail to block signaling via KIAA1549:BRAF, a truncation/fusion BRAF oncoprotein which functions as a dimer and is found in the most common form of PLGA. A panel of small molecule RAF inhibitors (including type II inhibitors, targeting the "DFG-out" conformation of the kinase) was screened for drugs showing efficacy on murine models of PLGA and on authentic human PLGA cells expressing KIAA1549:BRAF. We identify a type II RAF inhibitor that serves as an equipotent antagonist of BRAFV600E, KIAA1549:BRAF, and other noncanonical BRAF oncoproteins that function as dimers. This drug (MLN2480, also known as TAK-580) has good brain penetrance and is active on authentic human PLGA cells in brain organotypic cultures. MLN2480 may be an effective therapeutic for BRAF mutant pediatric astrocytomas. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Microstructural characterization and density change of 304 stainless steel reflector blocks after long-term irradiation in EBR-II

NASA Astrophysics Data System (ADS)

Huang, Y.; Wiezorek, J. M. K.; Garner, F. A.; Freyer, P. D.; Okita, T.; Sagisaka, M.; Isobe, Y.; Allen, T. R.

2015-10-01

While thin reactor structural components such as cladding and ducts do not experience significant gradients in dpa rate, gamma heating rate, temperature or stress, thick components can develop strong local variations in void swelling and irradiation creep in response to gradients in these variables. In this study we conducted microstructural investigations by transmission electron microscopy of two 52 mm thick 304-type stainless steel hex-blocks irradiated for 12 years in the EBR-II reactor with accumulated doses ranging from ∼0.4 to 33 dpa. Spatial variations in the populations of voids, precipitates, Frank loops and dislocation lines have been determined for 304 stainless steel sections exposed to different temperatures, different dpa levels and at different dpa rates, demonstrating the existence of spatial gradients in the resulting void swelling. The microstructural measurements compare very well with complementary density change measurements regarding void swelling gradients in the 304 stainless steel hex-block components. The TEM studies revealed that the original cold-worked-state microstructure of the unirradiated blocks was completely erased by irradiation, replaced by high densities of interstitial Frank loops, voids and carbide precipitates at both the lowest and highest doses. At large dose levels the amount of volumetric void swelling correlated directly with the gamma heating gradient-related temperature increase (e.g. for 28 dpa, ∼2% swelling at 418 °C and ∼2.9% swelling at 448 °C). Under approximately iso-thermal local conditions, volumetric void swelling was found to increase with dose level (e.g. ∼0.2% swelling at 0.4 dpa, ∼0.5% swelling at 4 dpa and ∼2% swelling at 28 dpa). Carbide precipitate formation levels were found to be relatively independent of both dpa level and temperature and induced a measurable densification. Void swelling was dominant at the higher dose levels and caused measurable decreases in density. Void swelling at the lowest doses was larger than might be expected based on the dpa level, an observation in agreement with earlier studies showing that the onset of void swelling is accelerated by decreasing dpa rates.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ha, Jung Min; Yun, Sung Ji; Kim, Young Whan

Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38more » MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. - Graphical abstract: Regulation of VSMC phenotype by PDGF-dependent activation of mTORC1. - Highlights: • The expression of contractile marker proteins was reduced by PDGF stimulation. • PDGF-dependent phenotypic conversion of VSMCs was blocked by inhibition of mTOR. • PDGF-induced proliferation of VSMCs was attenuated by inhibition of mTORC1. • mTORC1 plays a critical role in PDGF-dependent phenotypic conversion of VSMCs.« less

A synoptic and dynamical characterization of wave-train and blocking cold surge over East Asia

NASA Astrophysics Data System (ADS)

Park, Tae-Won; Ho, Chang-Hoi; Deng, Yi

2014-08-01

Through an agglomerative hierarchical clustering method, cold surges over East Asia are classified into two distinct types based on the spatial pattern of the geopotential height anomalies at 300 hPa. One is the wave-train type that is associated with developing large-scale waves across the Eurasian continent. The other is the blocking type whose occurrence accompanies subarctic blocking. During the wave-train cold surge, growing baroclinic waves induce a southeastward expansion of the Siberian High and strong northerly winds over East Asia. Blocking cold surge, on the other hand, is associated with a southward expansion of the Siberian High and northeasterly winds inherent to a height dipole consisting of the subarctic blocking and the East Asian coastal trough. The blocking cold surge tends to be more intense and last longer compared to the wave-train type. The wave-train cold surge is associated with the formation of a negative upper tropospheric height anomaly southeast of Greenland approximately 12 days before the surge occurrence. Further analysis of isentropic potential vorticity reveals that this height anomaly could originate from the lower stratosphere over the North Atlantic. Cold surge of the blocking type occurs with an amplifying positive geopotential and a negative potential vorticity anomaly over the Arctic and the northern Eurasia in stratosphere. These anomalies resemble the stratospheric signature of a negative phase of the Arctic Oscillation. This stratospheric feature is further demonstrated by the observation that the blocking type cold surge occurs more often when the Arctic Oscillation is in its negative phase.

Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

PubMed

Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

2016-09-01

Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Real Time Implementation of an LPC Algorithm. Speech Signal Processing Research at CHI

DTIC Science & Technology

1975-05-01

SIGNAL PROCESSING HARDWARE 2-1 2.1 INTRODUCTION 2-1 2.2 TWO- CHANNEL AUDIO SIGNAL SYSTEM 2-2 2.3 MULTI- CHANNEL AUDIO SIGNAL SYSTEM 2-5 2.3.1... Channel Audio Signal System 2-30 I ii kv^i^ünt«.jfc*. ji .„* ,:-v*. ’.ii. *.. ...... — ■ -,,.,-c-» —ipponp ■^ TOHaBWgBpwiBWgPlpaiPWgW v.«.wN...Messages .... 1-55 1-13. Lost or Out of Order Message 1-56 2-1. Block Diagram of Two- Channel Audio Signal System . . 2-3 2-2. Block Diagram of Audio

Effectiveness and efficiency of potassium fertilizer application to increase the production and quality of rice in entisols

NASA Astrophysics Data System (ADS)

Hartati, S.; Suryono; Purnomo, D.

2018-03-01

The study aimed to determine the appropriate dose of K-type fertilizer on the production and quality of IR-64 rice varieties in Entisols. The study was conducted on Entisols, Nglarang, Basin, Kebonarum, Klaten, Central Java, Indonesia. Randomized Complete Block Design (RCBD) was used with 2 factors and three replicates. Factor I: types of K fertilizer: KCl, ZK, and KNO3. Factor II: K fertilizer dose consists of four levels: 0, 50, 100 and 150 kg K2O ha-1. The results showed that the type of K fertilizer KCl, ZK, and KNO3 gave similar effect on growth and yield of rice variety IR 64 on Entisols. Dose of K fertilizer increased the growth and yield of rice but an increased dose provides improved meaningful results. K fertilizer with a dose of 50 kg ha-1 K2O is the most efficient, with the agronomic efficiency for dry grain highest yield of 13.6 kg/kg K2O achieved by ZK fertilizer.

Copper(II)-catalyzed trifluoromethylation of N-aryl imines.

PubMed

Zhang, Yong-Qiang; Liu, Ji-Dan; Xu, Hao

2013-10-07

Methods for imine trifluoromethylation are of great importance because amines with trifluoromethylated stereogenic centers are useful building blocks for synthetic chemistry and drug discovery. Herein, we describe a new copper(II)-catalyzed imine trifluoromethylation method without the use of Lewis base activators, presumably through cooperative activation.

Angiotensin II stimulates calcineurin activity in proximal tubule epithelia through AT-1 receptor-mediated tyrosine phosphorylation of the PLC-gamma1 isoform.

PubMed

Lea, Janice P; Jin, Shao G; Roberts, Brian R; Shuler, Michael S; Marrero, Mario B; Tumlin, James A

2002-07-01

Angiotensin II (AngII) contributes to the maintenance of extracellular fluid volume by regulating sodium transport in the nephron. In nonepithelial cells, activation of phospholipase C (PLC) by AT-1 receptors stimulates the generation of 1,4,5-trisphosphate (IP(3)) and the release of intracellular calcium. Calcineurin, a serine-threonine phosphatase, is activated by calcium and calmodulin, and both PLC and calcineurin have been linked to sodium transport in the proximal tubule. An examination of whether AngII activates calcineurin in a model of proximal tubule epithelia (LLC-PK1 cells) was performed; AngII increased calcineurin activity within 30 s. An examination of whether AngII activates PLC in proximal tubule epithelia was also performed after first showing that all three families of PLC isoforms are present in LLC-PK1 cells. Application of AngII increased IP(3) generation by 60% within 15 s, which coincided with AngII-induced tyrosine phosphorylation of the PLC-gamma1 isoform also observed at 15 s. AngII-induced tyrosine phosphorylation was blocked by the AT-1 receptor antagonist, Losartan. Subsequently, an inhibitor of tyrosine phosphorylation blocked the AngII-induced activation of calcineurin, as did coincubation with an inhibitor of PLC activity and with an antagonist of the AT-1 receptor. It is therefore concluded that AngII stimulates calcineurin phosphatase activity in proximal tubule epithelial cells through a mechanism involving AT-1 receptor-mediated tyrosine phosphorylation of the PLC isoform.

Control analysis of lipid biosynthesis in tissue cultures from oil crops shows that flux control is shared between fatty acid synthesis and lipid assembly.

PubMed Central

Ramli, Umi S; Baker, Darren S; Quant, Patti A; Harwood, John L

2002-01-01

Top-Down (Metabolic) Control Analysis (TDCA) was used to examine, quantitatively, lipid biosynthesis in tissue cultures from two commercially important oil crops, olive (Olea europaea L.) and oil palm (Elaeis guineensis Jacq.). A conceptually simplified system was defined comprising two blocks of reactions: fatty acid synthesis (Block A) and lipid assembly (Block B), which produced and consumed, respectively, a common and unique system intermediate, cytosolic acyl-CoA. We manipulated the steady-state levels of the system intermediate by adding exogenous oleic acid and, using two independent assays, measured the effect of the addition on the system fluxes (J(A) and J(B)). These were the rate of incorporation of radioactivity: (i) through Block A from [1-(14)C]acetate into fatty acids and (ii) via Block B from [U-(14)C]glycerol into complex lipids respectively. The data showed that fatty acid formation (Block A) exerted higher control than lipid assembly (Block B) in both tissues with the following group flux control coefficients (C):(i) Oil palm: *C(J(TL))(BlkA)=0.64+/-0.05 and *C(J(TL))(BlkB)=0.36+/-0.05(ii) Olive: *C(J(TL))(BlkA)=0.57+/-0.10 and *C(J(TL))(BlkB)=0.43+/-0.10where *C indicates the group flux control coefficient over the lipid biosynthesis flux (J(TL)) and the subscripts BlkA and BlkB refer to defined blocks of the system, Block A and Block B. Nevertheless, because both parts of the lipid biosynthetic pathway exert significant flux control, we suggest strongly that manipulation of single enzyme steps will not affect product yield appreciably. The present study represents the first use of TDCA to examine the overall lipid biosynthetic pathway in any tissue, and its findings are of immediate academic and economic relevance to the yield and nutritional quality of oil crops. PMID:12023882

Regulation of Xenopus laevis DNA topoisomerase I activity by phosphorylation in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaiserman, H.B.; Ingebritsen, T.S.; Benbow, R.M.

1988-05-03

DNA topoisomerase I has been purified to electrophoretic homogeneity from ovaries of the frog Xenopus laevis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the most purified fraction revealed a single major band at 110 kDa and less abundant minor bands centered at 62 kDa. Incubation of the most purified fraction with immobilized calf intestinal alkaline phosphatase abolished all DNA topoisomerase enzymatic activity in a time-dependent reaction. Treatment of the dephosphorylated X. laevis DNA topoisomerase I with a X. laevis casein kinase type II activity and ATP restored DNA topoisomerase activity to a level higher than that observed in the most purifiedmore » fraction. In vitro labeling experiments which employed the most purified DNA topoisomerase I fraction, (..gamma..-/sup 32/P)ATP, and the casein kinase type II enzyme showed that both the 110- and 62-kDa bands became phosphorylated in approximately molar proportions. Phosphoamino acid analysis showed that only serine residues became phosphorylated. Phosphorylation was accompanied by an increase in DNA topoisomerase activity in vitro. Dephosphorylation of DNA topoisomerase I appears to block formation of the initial enzyme-substrate complex on the basis of the failure of the dephosphorylated enzyme to nick DNA in the presence of camptothecin. The authors conclude that X. laevis DNA topoisomerase I is partially phosphorylated as isolated and that this phosphorylation is essential for expression of enzymatic activity in vitro. On the basis of the ability of the casein kinase type II activity to reactivate dephosphorylated DNA topoisomerase I, they speculate that this kinase may contribute to the physiological regulation of DNA topoisomerase I activity.« less

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

NASA Astrophysics Data System (ADS)

Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

2013-12-01

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.

PubMed

Lloyd, David J; St Jean, David J; Kurzeja, Robert J M; Wahl, Robert C; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S; Pennington, Lewis D; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H; Andrews, Kristin L; Bartberger, Michael D; Van, Gwyneth; Galbreath, Elizabeth J; Vonderfecht, Steven L; Wang, Minghan; Jordan, Steven R; Véniant, Murielle M; Hale, Clarence

2013-12-19

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

The Cryptic Competence Pathway in Streptococcus pyogenes Is Controlled by a Peptide Pheromone

PubMed Central

Mashburn-Warren, Lauren; Morrison, Donald A.

2012-01-01

Horizontal gene transfer is an important means of bacterial evolution that is facilitated by transduction, conjugation, and natural genetic transformation. Transformation occurs after bacterial cells enter a state of competence, where naked DNA is acquired from the extracellular environment. Induction of the competent state relies on signals that activate master regulators, causing the expression of genes involved in DNA uptake, processing, and recombination. All streptococcal species contain the master regulator SigX and SigX-dependent effector genes required for natural genetic transformation; however, not all streptococcal species have been shown to be naturally competent. We recently demonstrated that competence development in Streptococcus mutans requires the type II ComRS quorum-sensing circuit, comprising an Rgg transcriptional activator and a novel peptide pheromone (L. Mashburn-Warren, D. A. Morrison, and M. J. Federle, Mol. Microbiol. 78:589–606, 2010). The type II ComRS system is shared by the pyogenic, mutans, and bovis streptococci, including the clinically relevant pathogen Streptococcus pyogenes. Here, we describe the activation of sigX by a small-peptide pheromone and an Rgg regulator of the type II ComRS class. We confirm previous reports that SigX is functional and able to activate sigX-dependent gene expression within the competence regulon, and that SigX stability is influenced by the cytoplasmic protease ClpP. Genomic analyses of available S. pyogenes genomes revealed the presence of intact genes within the competence regulon. While this is the first report to show natural induction of sigX, S. pyogenes remained nontransformable under laboratory conditions. Using radiolabeled DNA, we demonstrate that transformation is blocked at the stage of DNA uptake. PMID:22730123

Blocking angiotensin II Type 1 receptor triggers apoptotic cell death in human pancreatic cancer cells.

PubMed

Gong, Qiaoke; Davis, Molly; Chipitsyna, Galina; Yeo, Charles J; Arafat, Hwyda A

2010-07-01

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy with an annual mortality rate close to its annual incidence. We recently demonstrated that angiotensin II (AngII) type 1 receptor (AT1R) might be involved in PDA angiogenesis. This study evaluated the antiproliferative and proapoptotic effects of an AT1R blocker, losartan, in PDA cells with different p53 mutation status. Cell cycle was analyzed by flow cytometric analysis of DNA content; apoptosis by annexin V-fluorescein isothiocyanate (V-FITC) and terminal deoxytransferase (TdT)-mediated dUTP nick-end labeling staining; messenger RNA and protein by real-time polymerase chain reaction and Western blotting; caspase-3 activity by colorimetric assay; and promoter activity by luciferase assay. Losartan dose-dependently decreased cell survival and increased their preG1 accumulation. It also increased p53, p21, p27, and Bax and reduced Bcl-2 and Bcl-xl expression. In wtp53 cells, losartan increased p53 transcription and activated caspase-3 in both cell lines. However, its proapoptotic effects in mtp53 cells were mainly caspase-3-dependent. Our data describe the involvement of AT1R in PDA cell apoptotic machinery and provide the first evidences that losartan stimulates the proapoptotic signaling pathways regardless of the p53 mutation status. As loss of p53 function is frequently observed in PDA patients, our data suggest AT1R blockade as a novel therapeutic strategy to control PDA growth.

Defining the reliability of sonoanatomy identification by novices in ultrasound-guided pediatric ilioinguinal and iliohypogastric nerve blockade.

PubMed

Ford, Simon; Dosani, Maryam; Robinson, Ashley J; Campbell, G Claire; Ansermino, J Mark; Lim, Joanne; Lauder, Gillian R

2009-12-01

The ilioinguinal (II)/iliohypogastric (IH) nerve block is a safe, frequently used block that has been improved in efficacy and safety by the use of ultrasound guidance. We assessed the frequency with which pediatric anesthesiologists with limited experience with ultrasound-guided regional anesthesia could correctly identify anatomical structures within the inguinal region. Our primary outcome was to compare the frequency of correct identification of the transversus abdominis (TA) muscle with the frequency of correct identification of the II/IH nerves. We used 2 ultrasound machines with different capabilities to assess a potential equipment effect on success of structure identification and time taken for structure identification. Seven pediatric anesthesiologists with <6 mo experience with ultrasound-guided regional anesthesia performed a total of 127 scans of the II region in anesthetized children. The muscle planes and the II and IH nerves were identified and labeled. The ultrasound images were reviewed by a blinded expert to mark accuracy of structure identification and time taken for identification. Two ultrasound machines (Sonosite C180plus and Micromaxx, both from Sonosite, Bothell, WA) were used. There was no difference in the frequency of correct identification of the TA muscle compared with the II/IH nerves (chi(2) test, TA versus II, P = 0.45; TA versus IH, P = 0.50). Ultrasound machine selection did show a nonsignificant trend in improving correct II/IH nerve identification (II nerve chi(2) test, P = 0.02; IH nerve chi(2) test, P = 0.04; Bonferroni corrected significance 0.17) but not for the muscle planes (chi(2) test, P = 0.83) or time taken (1-way analysis of variance, P = 0.07). A curve of improving accuracy with number of scans was plotted, with reliability of TA recognition occurring after 14-15 scans and II/IH identification after 18 scans. We have demonstrated that although there is no difference in the overall accuracy of muscle plane versus II/IH nerve identification, the muscle planes are reliably identified after fewer scans of the inguinal region. We suggest that a reliable end point for the inexperienced practitioner of ultrasound-guided II/IH nerve block may be the TA/internal oblique plane where the nerves are reported to be found in 100% of cases.

A role for midline and intralaminar thalamus in the associative blocking of Pavlovian fear conditioning.

PubMed

Sengupta, Auntora; McNally, Gavan P

2014-01-01

Fear learning occurs in response to positive prediction error, when the expected outcome of a conditioning trial exceeds that predicted by the conditioned stimuli present. This role for error in Pavlovian association formation is best exemplified by the phenomenon of associative blocking, whereby prior fear conditioning of conditioned stimulus (CS) A is able to prevent learning to CSB when they are conditioned in compound. The midline and intralaminar thalamic nuclei (MIT) are well-placed to contribute to fear prediction error because they receive extensive projections from the midbrain periaqueductal gray-which has a key role in fear prediction error-and project extensively to prefrontal cortex and amygdala. Here we used an associative blocking design to study the role of MIT in fear learning. In Stage I rats were trained to fear CSA via pairings with shock. In Stage II rats received compound fear conditioning of CSAB paired with shock. On test, rats that received Stage I training expressed less fear to CSB relative to control rats that did not receive this training. Microinjection of bupivacaine into MIT prior to Stage II training had no effect on the expression of fear during Stage II and had no effect on fear learning in controls, but prevented associative blocking and so enabled fear learning to CSB. These results show an important role for MIT in predictive fear learning and are discussed with reference to previous findings implicating the midline and posterior intralaminar thalamus in fear learning and fear responding.

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase

PubMed Central

Cozzoli, Anna; Liantonio, Antonella; Conte, Elena; Cannone, Maria; Massari, Ada Maria; Giustino, Arcangela; Scaramuzzi, Antonia; Pierno, Sabata; Mantuano, Paola; Capogrosso, Roberta Francesca; Camerino, Giulia Maria

2014-01-01

Angiotensin II (ANG II) plays a role in muscle wasting and remodeling; however, little evidence shows its direct effects on specific muscle functions. We presently investigated the acute in vitro effects of ANG II on resting ionic conductance and calcium homeostasis of mouse extensor digitorum longus (EDL) muscle fibers, based on previous findings that in vivo inhibition of ANG II counteracts the impairment of macroscopic ClC-1 chloride channel conductance (gCl) in the mdx mouse model of muscular dystrophy. By means of intracellular microelectrode recordings we found that ANG II reduced gCl in the nanomolar range and in a concentration-dependent manner (EC50 = 0.06 μM) meanwhile increasing potassium conductance (gK). Both effects were inhibited by the ANG II receptors type 1 (AT1)-receptor antagonist losartan and the protein kinase C inhibitor chelerythrine; no antagonism was observed with the AT2 antagonist PD123,319. The scavenger of reactive oxygen species (ROS) N-acetyl cysteine and the NADPH-oxidase (NOX) inhibitor apocynin also antagonized ANG II effects on resting ionic conductances; the ANG II-dependent gK increase was blocked by iberiotoxin, an inhibitor of calcium-activated potassium channels. ANG II also lowered the threshold for myofiber and muscle contraction. Both ANG II and the AT1 agonist L162,313 increased the intracellular calcium transients, measured by fura-2, with a two-step pattern. These latter effects were not observed in the presence of losartan and of the phospholipase C inhibitor U73122 and the in absence of extracellular calcium, disclosing a Gq-mediated calcium entry mechanism. The data show for the first time that the AT1-mediated ANG II pathway, also involving NOX and ROS, directly modulates ion channels and calcium homeostasis in adult myofibers. PMID:25080489

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase.

PubMed

Cozzoli, Anna; Liantonio, Antonella; Conte, Elena; Cannone, Maria; Massari, Ada Maria; Giustino, Arcangela; Scaramuzzi, Antonia; Pierno, Sabata; Mantuano, Paola; Capogrosso, Roberta Francesca; Camerino, Giulia Maria; De Luca, Annamaria

2014-10-01

Angiotensin II (ANG II) plays a role in muscle wasting and remodeling; however, little evidence shows its direct effects on specific muscle functions. We presently investigated the acute in vitro effects of ANG II on resting ionic conductance and calcium homeostasis of mouse extensor digitorum longus (EDL) muscle fibers, based on previous findings that in vivo inhibition of ANG II counteracts the impairment of macroscopic ClC-1 chloride channel conductance (gCl) in the mdx mouse model of muscular dystrophy. By means of intracellular microelectrode recordings we found that ANG II reduced gCl in the nanomolar range and in a concentration-dependent manner (EC50 = 0.06 μM) meanwhile increasing potassium conductance (gK). Both effects were inhibited by the ANG II receptors type 1 (AT1)-receptor antagonist losartan and the protein kinase C inhibitor chelerythrine; no antagonism was observed with the AT2 antagonist PD123,319. The scavenger of reactive oxygen species (ROS) N-acetyl cysteine and the NADPH-oxidase (NOX) inhibitor apocynin also antagonized ANG II effects on resting ionic conductances; the ANG II-dependent gK increase was blocked by iberiotoxin, an inhibitor of calcium-activated potassium channels. ANG II also lowered the threshold for myofiber and muscle contraction. Both ANG II and the AT1 agonist L162,313 increased the intracellular calcium transients, measured by fura-2, with a two-step pattern. These latter effects were not observed in the presence of losartan and of the phospholipase C inhibitor U73122 and the in absence of extracellular calcium, disclosing a Gq-mediated calcium entry mechanism. The data show for the first time that the AT1-mediated ANG II pathway, also involving NOX and ROS, directly modulates ion channels and calcium homeostasis in adult myofibers. Copyright © 2014 the American Physiological Society.

A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

PubMed Central

Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

2015-01-01

Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

Tripeptidyl peptidase II promotes fat formation in a conserved fashion.

PubMed

McKay, Renée M; McKay, James P; Suh, Jae Myoung; Avery, Leon; Graff, Jonathan M

2007-12-01

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner.

Tripeptidyl peptidase II promotes fat formation in a conserved fashion

PubMed Central

McKay, Renée M; McKay, James P; Suh, Jae Myoung; Avery, Leon; Graff, Jonathan M

2007-01-01

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner. PMID:17932511

Omentin-1 prevents cartilage matrix destruction by regulating matrix metalloproteinases.

PubMed

Li, Zhigang; Liu, Baoyi; Zhao, Dewei; Wang, BenJie; Liu, Yupeng; Zhang, Yao; Li, Borui; Tian, Fengde

2017-08-01

Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the extracellular matrix and pathological progression of osteoarthritis (OA). Omentin-1 is a newly identified anti-inflammatory adipokine. Little information regarding the protective effects of omentin-1 in OA has been reported before. In the current study, our results indicated that omentin-1 suppressed expression of MMP-1, MMP-3, and MMP-13 induced by the proinflammatory cytokine interleukin-1β (IL-1β) at both the mRNA and protein levels in human chondrocytes. Importantly, administration of omentin-1 abolished IL-1β-induced degradation of type II collagen (Col II) and aggrecan, the two major extracellular matrix components in articular cartilage, in a dose-dependent manner. Mechanistically, omentin-1 ameliorated the expression of interferon regulatory factor 1 (IRF-1) by blocking the JAK-2/STAT3 pathway. Our results indicate that omentin-1 may have a potential chondroprotective therapeutic capacity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Molecular basis of proton block of L-type Ca2+ channels.

PubMed

Chen, X H; Bezprozvanny, I; Tsien, R W

1996-11-01

Hydrogen ions are important regulators of ion flux through voltage-gated Ca2+ channels but their site of action has been controversial. To identify molecular determinants of proton block of L-type Ca2+ channels, we combined site-directed mutagenesis and unitary current recordings from wild-type (WT) and mutant L-type Ca2+ channels expressed in Xenopus oocytes. WT channels in 150 mM K+ displayed two conductance states, deprotonated (140 pS) and protonated (45 pS), as found previously in native L-type Ca2+ channels. Proton block was altered in a unique fashion by mutation of each of the four P-region glutamates (EI-EIV) that form the locus of high affinity Ca2+ interaction. Glu(E)-->Gln(Q) substitution in either repeats I or III abolished the high-conductance state, as if the titration site had become permanently protonated. While the EIQ mutant displayed only an approximately 40 pS conductance, the EIIIQ mutant showed the approximately 40 pS conductance plus additional pH-sensitive transitions to an even lower conductance level. The EIVQ mutant exhibited the same deprotonated and protonated conductance states as WT, but with an accelerated rate of deprotonation. The EIIQ mutant was unusual in exhibiting three conductance states (approximately 145, 102, 50 pS, respectively). Occupancy of the low conductance state increased with external acidification, albeit much higher proton concentration was required than for WT. In contrast, the equilibrium between medium and high conductance levels was apparently pH-insensitive. We concluded that the protonation site in L-type Ca2+ channels lies within the pore and is formed by a combination of conserved P-region glutamates in repeats I, II, and III, acting in concert. EIV lies to the cytoplasmic side of the site but exerts an additional stabilizing influence on protonation, most likely via electrostatic interaction. These findings are likely to hold for all voltage-gated Ca2+ channels and provide a simple molecular explanation for the modulatory effect of H+ ions on open channel flux and the competition between H+ ions and permeant divalent cations. The characteristics of H+ interactions advanced our picture of the functional interplay between P-region glutamates, with important implications for the mechanism of Ca2+ selectivity and permeation.

Insulin-like growth factor-I (lGF-l): safety and efficacy.

PubMed

Laron, Zvi

2004-11-01

Insulin-like growth factor I (IGF-I) is a peptide synthesized mainly in the liver by stimulation by pituitary growth hormone (GH). It circulates almost entirely bound to its binding proteins. It is the anabolic effector hormone of GH. It is the only treatment in states of GH resistance such as Laron syndrome and blocking antibodies to human GH. As it suppresses insulin and GH secretion it has been used in states of insulin resistance including Type II diabetes mellitus. IGF-I is administered by once or twice daily injections. Adverse effects are mostly caused by overdosage. The usual daily dose in children ranges from 100-200 microg/kg.

17 CFR 240.16a-7 - Transactions effected in connection with a distribution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... good faith in the distribution of such block of securities; or (ii) A security purchased in good faith... the transaction is engaged in the business of distributing securities and is participating in good faith, in the ordinary course of such business, in the distribution of such block of securities; and (2...

76 FR 11315 - Blocking Property and Prohibiting Certain Transactions Related to Libya

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... Secretary of State: (i) to be a senior official of the Government of Libya; (ii) to be a child of Colonel... otherwise directing, or to have participated in, the commission of human rights abuses related to political...) to be a spouse or dependent child of any person whose property and interests in property are blocked...

48 CFR 50.205-3 - Authorization of offers contingent upon SAFETY Act designation or certification before contract...

Code of Federal Regulations, 2011 CFR

2011-10-01

...— (i) For offers contingent upon SAFETY Act designation, a pre-qualification designation notice or a block designation; or (ii) For offers contingent upon SAFETY Act certification, a block certification... contingent upon SAFETY Act designation or certification before contract award. 50.205-3 Section 50.205-3...

Military Curricula for Vocational & Technical Education. Metals Processing Specialist, Blocks I and II, Classroom Course 13-5.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

These curriculum materials are the first section of a four-part, secondary-postsecondary-level course in metals processing. The course is one of a number of military-developed curriculum packages selected for adaptation to vocational instruction and curriculum development in a civilian setting. Block I, Introduction to Oxyacetylene Welding,…

Multiple brain networks underpinning word learning from fluent speech revealed by independent component analysis.

PubMed

López-Barroso, Diana; Ripollés, Pablo; Marco-Pallarés, Josep; Mohammadi, Bahram; Münte, Thomas F; Bachoud-Lévi, Anne-Catherine; Rodriguez-Fornells, Antoni; de Diego-Balaguer, Ruth

2015-04-15

Although neuroimaging studies using standard subtraction-based analysis from functional magnetic resonance imaging (fMRI) have suggested that frontal and temporal regions are involved in word learning from fluent speech, the possible contribution of different brain networks during this type of learning is still largely unknown. Indeed, univariate fMRI analyses cannot identify the full extent of distributed networks that are engaged by a complex task such as word learning. Here we used Independent Component Analysis (ICA) to characterize the different brain networks subserving word learning from an artificial language speech stream. Results were replicated in a second cohort of participants with a different linguistic background. Four spatially independent networks were associated with the task in both cohorts: (i) a dorsal Auditory-Premotor network; (ii) a dorsal Sensory-Motor network; (iii) a dorsal Fronto-Parietal network; and (iv) a ventral Fronto-Temporal network. The level of engagement of these networks varied through the learning period with only the dorsal Auditory-Premotor network being engaged across all blocks. In addition, the connectivity strength of this network in the second block of the learning phase correlated with the individual variability in word learning performance. These findings suggest that: (i) word learning relies on segregated connectivity patterns involving dorsal and ventral networks; and (ii) specifically, the dorsal auditory-premotor network connectivity strength is directly correlated with word learning performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Free fatty acids block glucose-induced β-cell proliferation in mice by inducing cell cycle inhibitors p16 and p18.

PubMed

Pascoe, Jordan; Hollern, Douglas; Stamateris, Rachel; Abbasi, Munira; Romano, Lia C; Zou, Baobo; O'Donnell, Christopher P; Garcia-Ocana, Adolfo; Alonso, Laura C

2012-03-01

Pancreatic β-cell proliferation is infrequent in adult humans and is not increased in type 2 diabetes despite obesity and insulin resistance, suggesting the existence of inhibitory factors. Free fatty acids (FFAs) may influence proliferation. In order to test whether FFAs restrict β-cell proliferation in vivo, mice were intravenously infused with saline, Liposyn II, glucose, or both, continuously for 4 days. Lipid infusion did not alter basal β-cell proliferation, but blocked glucose-stimulated proliferation, without inducing excess β-cell death. In vitro exposure to FFAs inhibited proliferation in both primary mouse β-cells and in rat insulinoma (INS-1) cells, indicating a direct effect on β-cells. Two of the fatty acids present in Liposyn II, linoleic acid and palmitic acid, both reduced proliferation. FFAs did not interfere with cyclin D2 induction or nuclear localization by glucose, but increased expression of inhibitor of cyclin dependent kinase 4 (INK4) family cell cycle inhibitors p16 and p18. Knockdown of either p16 or p18 rescued the antiproliferative effect of FFAs. These data provide evidence for a novel antiproliferative form of β-cell glucolipotoxicity: FFAs restrain glucose-stimulated β-cell proliferation in vivo and in vitro through cell cycle inhibitors p16 and p18. If FFAs reduce proliferation induced by obesity and insulin resistance, targeting this pathway may lead to new treatment approaches to prevent diabetes.

STUDIES ON ISOLATED NUCLEI. II. ISOLATION AND CHEMICAL CHARACTERIZATION OF NUCLEOLAR AND NUCLEOPLASMIC SUBFRACTIONS.

PubMed

MAGGIO, R; SIEKEVITZ, P; PALADE, G E

1963-08-01

This paper describes the subfractionation of nuclei isolated from guinea pig liver by the procedure presented in the first article of the series (8). Centrifugation in a density gradient system of nuclear fractions disrupted by sonication permits the isolation of the following subfractions: (a) a nucleolar subfraction which consists mainly of nucleoli surrounded by a variable amount of nucleolus-associated chromatin and contaminated by chromatin blocks derived primarily from von Kupffer cell nuclei; (b) and (c), two nucleoplasmic subfractions (I and II) which consist mainly of chromatin threads in a coarser (I) or finer (II) degree of fragmentation. The protein, RNA, and DNA content of these subfractions was determined, and their RNA's characterized in terms of NaCl-solubility, nucleotide composition, and in vivo nucleotide turnover, using inorganic (32)P as a marker. The results indicate that there are at least three types of RNA in the nucleus (one in the nucleolus and two in the nucleoplasm or chromatin), which differ from one another in NaCl-solubility, nucleotide composition, turnover, and possibly sequence. Possible relations among these RNA's and those of the cytoplasm are discussed.

Design of lateral heterostructure from arsenene and antimonene

NASA Astrophysics Data System (ADS)

Sun, Qilong; Dai, Ying; Ma, Yandong; Yin, Na; Wei, Wei; Yu, Lin; Huang, Baibiao

2016-09-01

Lateral heterostructures fabricated by two-dimensional building blocks have opened up exciting realms in material science and device physics. Identifying suitable materials for creating such heterostructures is urgently needed for the next-generation devices. Here, we demonstrate a novel type of seamless lateral heterostructures with excellent stabilities formed within pristine arsenene and antimonene. We find that these heterostructures could possess direct and reduced energy gaps without any modulations. Moreover, the highly coveted type-II alignment and the high carrier mobility are also identified, marking the enhanced quantum efficiency. The tensile strain can result in efficient bandgap engineering. Besides, the proposed critical condition for favored direct energy gaps would have a guiding significance on the subsequent works. Generally, our predictions not only introduce new vitality into lateral heterostructures, enriching available candidate materials in this field, but also highlight the potential of these lateral heterostructures as appealing materials for future devices.

45 CFR 96.87 - Leveraging incentive program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Low-income... paragraphs (a)(2)(ii) and (a)(2)(iii) of this section. (ii) Indian tribes that received LIHEAP services under... resources leveraged by the tribe are reported, and the tribe receives LIHEAP services under section 2602(b...

45 CFR 96.87 - Leveraging incentive program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Low-income... paragraphs (a)(2)(ii) and (a)(2)(iii) of this section. (ii) Indian tribes that received LIHEAP services under... resources leveraged by the tribe are reported, and the tribe receives LIHEAP services under section 2602(b...

30 CFR 75.222 - Roof control plan-approval criteria.

Code of Federal Regulations, 2014 CFR

2014-07-01

... systems. (1) Systematic supplemental support should be installed throughout— (i) The tailgate entry of the first longwall panel prior to any mining; and (ii) In the proposed tailgate entry of each subsequent... should address— (i) Notification of miners that the travelway is blocked; (ii) Re-instruction of miners...

30 CFR 75.222 - Roof control plan-approval criteria.

Code of Federal Regulations, 2012 CFR

2012-07-01

... systems. (1) Systematic supplemental support should be installed throughout— (i) The tailgate entry of the first longwall panel prior to any mining; and (ii) In the proposed tailgate entry of each subsequent... should address— (i) Notification of miners that the travelway is blocked; (ii) Re-instruction of miners...

30 CFR 75.222 - Roof control plan-approval criteria.

Code of Federal Regulations, 2013 CFR

2013-07-01

... systems. (1) Systematic supplemental support should be installed throughout— (i) The tailgate entry of the first longwall panel prior to any mining; and (ii) In the proposed tailgate entry of each subsequent... should address— (i) Notification of miners that the travelway is blocked; (ii) Re-instruction of miners...

Transmittance of tinted and UV-blocking disposable contact lenses.

PubMed

Harris, M G; Haririfar, M; Hirano, K Y

1999-03-01

Tinted and ultraviolet (UV)-blocking disposable contact lenses have become increasingly popular over the last decade. Wearers of UV-blocking contact lenses could benefit greatly by protecting their eyes from potential UV radiation damage. A Uvikon 930 dual beam spectrophotometer was used to measure three enhancement-tinted lenses (royal blue, evergreen, and aqua), two types of UV-blocking lenses, and two types of non-UV-blocking lenses. Enhancement-tinted lenses did show a decrease in transmittance at certain wavelengths on the visible spectrum, but they did not reduce the transmittance of UV radiation to the extent of the UV-blocking lenses designed specifically for this purpose.

S-Glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans

PubMed Central

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-01-01

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10µCa2+½ at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mm) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnIf) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnIf were blocked by N-ethylmaleimide (NEM). S-Nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnIf. In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnIf. When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnIf, DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnIf (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnIf in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnIf, most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance. PMID:22250211

S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

PubMed

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-03-15

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnI(f) (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnI(f) in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnI(f), most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance.

Wessex Helicopter/Sonar Dynamics Study. ARL Program Description and Operation.

DTIC Science & Technology

1979-02-01

s): 5. Document Date: S illiams, Neil V. February, 1979 Guy, Christopher R. Williams, Maxwell J. 6. Type of Report and Period Covered: Gilbert, Neil...form with the aid of an analog computer type of block diagram, comprising a number of linked modules (called blocks), each one representing a particular...three types of statement, viz. configuration, parameter and function statements. The configuration statements describe the blocks used and specify the

Conformal Nets II: Conformal Blocks

NASA Astrophysics Data System (ADS)

Bartels, Arthur; Douglas, Christopher L.; Henriques, André

2017-08-01

Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

The TCP4 transcription factor of Arabidopsis blocks cell division in yeast at G1→S transition.

PubMed

Aggarwal, Pooja; Padmanabhan, Bhavna; Bhat, Abhay; Sarvepalli, Kavitha; Sadhale, Parag P; Nath, Utpal

2011-07-01

The TCP transcription factors control important aspects of plant development. Members of class I TCP proteins promote cell cycle by regulating genes directly involved in cell proliferation. In contrast, members of class II TCP proteins repress cell division. While it has been postulated that class II proteins induce differentiation signal, their exact role on cell cycle has not been studied. Here, we report that TCP4, a class II TCP protein from Arabidopsis that repress cell proliferation in developing leaves, inhibits cell division by blocking G1→S transition in budding yeast. Cells expressing TCP4 protein with increased transcriptional activity fail to progress beyond G1 phase. By analyzing global transcriptional status of these cells, we show that expression of a number of cell cycle genes is altered. The possible mechanism of G1→S arrest is discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Acceleration of block-matching algorithms using a custom instruction-based paradigm on a Nios II microprocessor

NASA Astrophysics Data System (ADS)

González, Diego; Botella, Guillermo; García, Carlos; Prieto, Manuel; Tirado, Francisco

2013-12-01

This contribution focuses on the optimization of matching-based motion estimation algorithms widely used for video coding standards using an Altera custom instruction-based paradigm and a combination of synchronous dynamic random access memory (SDRAM) with on-chip memory in Nios II processors. A complete profile of the algorithms is achieved before the optimization, which locates code leaks, and afterward, creates a custom instruction set, which is then added to the specific design, enhancing the original system. As well, every possible memory combination between on-chip memory and SDRAM has been tested to achieve the best performance. The final throughput of the complete designs are shown. This manuscript outlines a low-cost system, mapped using very large scale integration technology, which accelerates software algorithms by converting them into custom hardware logic blocks and showing the best combination between on-chip memory and SDRAM for the Nios II processor.

Chronic shin splints. Classification and management of medial tibial stress syndrome.

PubMed

Detmer, D E

1986-01-01

A clinical classification and treatment programme has been developed for chronic medial tibial stress syndrome. Medial tibial stress syndrome has been reported to be either tibial stress fracture or microfracture, tibial periostitis, or distal deep posterior chronic compartment syndrome. Three chronic types exist and may coexist: Type I (tibial microfracture, bone stress reaction or cortical fracture); type II (periostalgia from chronic avulsion of the periosteum at the periosteal-fascial junction); and type III (chronic compartment syndrome syndrome). Type I disease is treated nonoperatively. Operations for resistant types II and III medial tibial stress syndrome were performed in 41 patients. Bilaterality was common (type II, 50% type III, 88%). Seven had coexistent type II/III; one had type I/II. Preoperative symptoms averaged 24 months in type II, 6 months in type III, and 33 months in types II/III. Mean age was 22 years (15 to 51). Resting compartment pressures were normal in type II (mean 12 mm Hg) and elevated in type III and type II/III (mean 23 mm Hg). Type II and type II/III patients received fasciotomy plus periosteal cauterisation. Type III patients had fasciotomy only. All procedures were performed on an outpatient basis using local anaesthesia. Follow up was complete and averaged 6 months (2 to 14 months). Improved performance was as follows: type II, 93%, type III, 100%; type II/III, 86%. Complete cures were as follows: type II, 78%; type III, 75%; and type II/III, 57%. This experience suggests that with precise diagnosis and treatment involving minimal risk and cost the athlete has a reasonable chance of return to full activity.

Novel mechanism of cardiac protection by valsartan: synergetic roles of TGF-β1 and HIF-1α in Ang II-mediated fibrosis after myocardial infarction

PubMed Central

Sui, Xizhong; Wei, Hongchao; Wang, Dacheng

2015-01-01

Transforming growth factor (TGF)-β1 is a known factor in angiotensin II (Ang II)-mediated cardiac fibrosis after myocardial infarction (MI). Hypoxia inducible factor-1 (Hif-1α) was recently demonstrated to involve in the tissue fibrosis and influenced by Ang II. However, whether Hif-1α contributed to the Ang II-mediated cardiac fibrosis after MI, and whether interaction or synergetic roles between Hif-1α and TGF-β pathways existed in the process was unclear. In vitro, cardiac cells were incubated under hypoxia or Ang II to mimic ischaemia. In vivo, valsartan was intravenously injected into Sprague–Dawley rats with MI daily for 1 week; saline and hydralazine (another anti-hypertensive agent like valsartan) was used as control. The fibrosis-related proteins were detected by Western blotting. Cardiac structure and function were assessed with multimodality methods. We demonstrated in vitro that hypoxia would induce the up-regulation of Ang II, TGF-β/Smad and Hif-1α, which further induced collagen accumulation. By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up-regulation of TGF-β/Smad and Hif-1α was through the Ang II-mediated pathway. By administering TGF-β or dimethyloxalylglycine, we determined that both TGF-β/Smad and Hif-1α contributed to Ang II-mediated collagen accumulation and a synergetic effect between them was observed. Consistent with in vitro results, valsartan significantly attenuated the expression of TGF-β/Smad, Hif-1α and fibrosis-related protein in rats after MI. Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine. Our study may provide novel insights into the mechanisms of Ang II-induced cardiac fibrosis as well as into the cardiac protection of valsartan. PMID:25823960

Fast intraslab fluid-flow events linked to pulses of high pore fluid pressure at the subducted plate interface

NASA Astrophysics Data System (ADS)

Taetz, Stephan; John, Timm; Bröcker, Michael; Spandler, Carl; Stracke, Andreas

2018-01-01

A better understanding of the subduction zone fluid cycle and its chemical-mechanical feedback requires in-depth knowledge about how fluids flow within and out of descending slabs. Relicts of fluid-flow systems in exhumed rocks of fossil subduction zones allow for identification of the general relationships between dehydration reactions, fluid pathway formation, the dimensions and timescales of distinct fluid flow events; all of which are required for quantitative models for fluid-induced subduction zone processes. Two types of garnet-quartz-phengite veins can be distinguished in an eclogite-facies mélange block from the Pouébo Eclogite Mélange, New Caledonia. These veins record synmetamorphic internal fluid release by mineral breakdown reactions (type I veins), and infiltration of an external fluid (type II veins) with the associated formation of a reaction selvage. The dehydration and fluid migration documented by the type I veins likely occurred on a timescale of 105-106 years, based on average subduction rates and metamorphic conditions required for mineral dehydration and fluid flow. The timeframe of fluid-rock interaction between the external fluid and the wall-rock of the type II veins is quantified using a continuous bulk-rock Li-diffusion profile perpendicular to a vein and its metasomatic selvage. Differences in Li concentration between the internal and external fluid reservoirs resulted in a distinct diffusion profile (decreasing Li concentration and increasing δ7 Li) as the reaction front propagated into the host rock. Li-chronometric constraints indicate that the timescales of fluid-rock interaction associated with type II vein formation are on the order of 1 to 4 months (0.150-0.08+0.14 years). The short-lived, pulse-like character of this process is consistent with the notion that fluid flow caused by oceanic crust dehydration at the blueschist-to-eclogite transition contributes to or even dominates episodic pore fluid pressure increases at the plate interface, which in turn, may trigger slip events reported from many subduction zones.

Optimization of Blocked Designs in fMRI Studies

ERIC Educational Resources Information Center

Maus, Barbel; van Breukelen, Gerard J. P.; Goebel, Rainer; Berger, Martijn P. F.

2010-01-01

Blocked designs in functional magnetic resonance imaging (fMRI) are useful to localize functional brain areas. A blocked design consists of different blocks of trials of the same stimulus type and is characterized by three factors: the length of blocks, i.e., number of trials per blocks, the ordering of task and rest blocks, and the time between…

Cellular Trojan horse based polymer nanoreactors with light-sensitive activity.

PubMed

Baumann, Patric; Spulber, Mariana; Dinu, Ionel Adrian; Palivan, Cornelia G

2014-08-07

Stimulus-sensitive systems at the nanoscale represent ideal candidates for improving therapeutic and diagnostic approaches by producing rapid responses to the presence of specific molecules or conditions either by changing properties or by acting "on demand". Here we introduce an optimized light-sensitive nanoreactor based on encapsulation of a photosensitizer inside polymer vesicles to serve as an efficient source of reactive oxygen species (ROS) "on demand". Two types of amphiphilic block copolymers, poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline), PMOXA-PDMS-PMOXA, and poly(N-vinylpyrrolidone)-block-poly(dimethylsiloxane)-block-poly(N-vinylpyrrolidone), PNVP-PDMS-PNVP, were used to encapsulate Rose Bengal-bovine serum albumin (RB-BSA) inside the cavity of vesicles. The difference of copolymers molecular properties (hydrophobic to hydrophilic ratio, different chemical nature of the hydrophilic block) influenced the encapsulation ability, and uptake by cells, allowing therefore a selection of the most efficient polymer system. Nanoreactors were optimized in terms of (i) size, (ii) stability, and (iii) encapsulation efficiency based on a combination of light scattering, TEM, and UV-vis spectroscopy. By illumination, encapsulated RB-BSA conjugates generated in situ ROS, which diffused through the polymer membrane to the environment of the vesicles, as proved by electron spin resonance spectroscopy (ESR). Optimum illumination conditions were obtained based on the effect of the illumination time on the amount of ROS produced in situ by the encapsulated RB-BSA conjugates. ROS diffusion monitored by ESR was dependent on the molecular weight of copolymer that influences the thickness of the polymer membrane. Upon uptake into HeLa cells our nontoxic nanoreactors acted as a Trojan horse: they produced illumination-controlled ROS in sufficient amounts to induce cell death under photodynamic therapy (PDT) conditions. Straightforward production, stability, and Trojan horse activity inside cells support our light-sensitive nanoreactors for medical applications which require ROS to be generated with precise time and space control.

Safinamide.

PubMed

Fariello, Ruggero G

2007-01-01

Safinamide (SAF) ((S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino)propanamide) was initially synthetized by Farmitalia Carlo Erba (Italy). Following initial anticonvulsant screening, safinamide was selected for its potency, broad spectrum of action, and good safety margin. Pharmacodynamic properties probably relevant to its antiepileptic activity are use- and frequency-dependent block of voltage sensitive Na+ channels, block of Ca++ channels, and glutamate release inhibition. Possibly contributing mechanism are also selective and reversible monoamide oxidase B inhibition and dopamine and noradrenaline uptake inhibition. The high selectivity for the sigma-1 receptor site does not entail psychotomimetic or behavioral changes. In several experimental in vitro and in vivo conditions, SAF exerts neurorescuing and neuroprotectant effects. Safinamide is water soluble and suitable for 1 times a day oral administration in humans. In a pilot phase II study in 38 refractory epilepsy patients affected by multiple types of seizures, 41% of subjects obtained > or =50% seizure reduction during a 12-week escalating dose up to 300 mg 1 times day compared with perspective baseline. Safinamide is being developed in phase III for treatment of Parkinson's disease, whereas the development in epilepsy relates to the industrial strategy of the company.

Superlattice infrared photodetector research at the Jet Propulsion Laboratory

NASA Astrophysics Data System (ADS)

Gunapala, S. D.; Ting, D. Z.; Rafol, S. B.; Soibel, A.; Khoshakhlagh, A.; Hill, C. J.; Höglund, L.; Keo, S. A.; Liu, J. K.; Mumolo, J. M.; Luong, E. M.; Fisher, A.

2015-08-01

III-V semiconductors offer a highly effective platform for the development of sophisticated heterostructure-based MWIR and LWIR detectors, as exemplified by the high-performance double heterstructure (DH) nBn, XBn, and type- II superlattice infrared detectors. A key enabling design element is the unipolar barrier, which is used to implement the complementary barrier infra-red detector (CBIRD) design for increasing the collection efficiency of photogenerated carriers, and reducing dark current generation without impeding photocurrent flow. Heterostructure superlattice detectors that make effective use of unipolar barriers have demonstrated strong reduction of generationrecombination (G-R) dark current due to Shockley-Read-Hall (SRH) processes. In the last several years we solely focused on the development of antimonide based IR detectors. Recently, we demonstrated RoA values over 14,000 Ohm cm2 for a 9.9 μm cutoff device by incorporating electron-blocking and hole-blocking unipolar barriers. This device has shown 300K BLIP operation with f/2 optics at 87 K with blackbody * of 1.1x1011 cm Hz1/2/W.

Inhibition of CRISPR-Cas9 with Bacteriophage Proteins.

PubMed

Rauch, Benjamin J; Silvis, Melanie R; Hultquist, Judd F; Waters, Christopher S; McGregor, Michael J; Krogan, Nevan J; Bondy-Denomy, Joseph

2017-01-12

Bacterial CRISPR-Cas systems utilize sequence-specific RNA-guided nucleases to defend against bacteriophage infection. As a countermeasure, numerous phages are known that produce proteins to block the function of class 1 CRISPR-Cas systems. However, currently no proteins are known to inhibit the widely used class 2 CRISPR-Cas9 system. To find these inhibitors, we searched cas9-containing bacterial genomes for the co-existence of a CRISPR spacer and its target, a potential indicator for CRISPR inhibition. This analysis led to the discovery of four unique type II-A CRISPR-Cas9 inhibitor proteins encoded by Listeria monocytogenes prophages. More than half of L. monocytogenes strains with cas9 contain at least one prophage-encoded inhibitor, suggesting widespread CRISPR-Cas9 inactivation. Two of these inhibitors also blocked the widely used Streptococcus pyogenes Cas9 when assayed in Escherichia coli and human cells. These natural Cas9-specific "anti-CRISPRs" present tools that can be used to regulate the genome engineering activities of CRISPR-Cas9. Copyright © 2017 Elsevier Inc. All rights reserved.

Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression.

PubMed

Gnirss, Kerstin; Kühl, Annika; Karsten, Christina; Glowacka, Ilona; Bertram, Stephanie; Kaup, Franziska; Hofmann, Heike; Pöhlmann, Stefan

2012-03-01

Ebola (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever. The host cell proteases cathepsin B and L activate the Zaire ebolavirus glycoprotein (GP) for cellular entry and constitute potential targets for antiviral intervention. However, it is unclear if different EBOV species and MARV equally depend on cathepsin B/L activity for infection of cell lines and macrophages, important viral target cells. Here, we show that cathepsin B/L inhibitors markedly reduce 293T cell infection driven by the GPs of all EBOV species, independent of the type II transmembrane serine protease TMPRSS2, which cleaved but failed to activate EBOV-GPs. Similarly, a cathepsin B/L inhibitor blocked macrophage infection mediated by different EBOV-GPs. In contrast, MARV-GP-driven entry exhibited little dependence on cathepsin B/L activity. Still, MARV-GP-mediated entry was efficiently blocked by leupeptin. These results suggest that cathepsins B/L promote entry of EBOV while MARV might employ so far unidentified proteases for GP activation. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhibition Mechanism of an Anti-CRISPR Suppressor AcrIIA4 Targeting SpyCas9.

PubMed

Yang, Hui; Patel, Dinshaw J

2017-07-06

Prokaryotic CRISPR-Cas adaptive immune systems utilize sequence-specific RNA-guided endonucleases to defend against infection by viruses, bacteriophages, and mobile elements, while these foreign genetic elements evolve diverse anti-CRISPR proteins to overcome the CRISPR-Cas-mediated defense of the host. Recently, AcrIIA2 and AcrIIA4, encoded by Listeria monocytogene prophages, were shown to block the endonuclease activity of type II-A Streptococcus pyogene Cas9 (SpyCas9). We now report the crystal structure of AcrIIA4 in complex with single-guide RNA-bound SpyCas9, thereby establishing that AcrIIA4 preferentially targets critical residues essential for PAM duplex recognition, as well as blocks target DNA access to key catalytic residues lining the RuvC pocket. These structural insights, validated by biochemical assays on key mutants, demonstrate that AcrIIA4 competitively occupies both PAM-interacting and non-target DNA strand cleavage catalytic pockets. Our studies provide insights into anti-CRISPR-mediated suppression mechanisms for inactivating SpyCas9, thereby broadening the applicability of CRISPR-Cas regulatory tools for genome editing. Published by Elsevier Inc.

Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin.

PubMed

Uneda, Kazushi; Wakui, Hiromichi; Maeda, Akinobu; Azushima, Kengo; Kobayashi, Ryu; Haku, Sona; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Matsuda, Miyuki; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Toya, Yoshiyuki; Atobe, Yoshitoshi; Yamashita, Akio; Umemura, Satoshi; Tamura, Kouichi

2017-07-27

The kidney is easily affected by aging-associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP), which was originally identified as a molecule that binds to AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT1R signaling, but does not affect physiological AT1R signaling. We hypothesized that ATRAP has a novel functional role in the physiological age-degenerative process, independent of modulation of AT1R signaling. ATRAP-knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a normal age-associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP-knockout mice compared with wild-type mice, the following takes place: (1) age-associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild-type mice. These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

A new dynamical index for classification of cold surge types over East Asia

NASA Astrophysics Data System (ADS)

Park, Tae-Won; Ho, Chang-Hoi; Jeong, Jee-Hoon; Heo, Jin-Woo; Deng, Yi

2015-11-01

The cold surges over East Asia can be classified into wave-train type and blocking type according to their dynamic origins. In the present study, two dynamic indices are proposed to objectively identify cold surge types using potential temperature ( θ) on the dynamic tropopause at 2-potential vorticity units (2-PVU) surface. The two indices are designed to represent primary characteristics of the two types of cold surge. The wave-train index ( WI) is defined as a difference of anomalous θ on the 2-PVU surface between the western North Pacific and northeast China, which captures a southward (northward) intrusion of cold (warm) air mass related to the trough-ridge pattern. The blocking index ( BI) is defined as a difference of anomalous θ between the subarctic region and northeast China, which indicates air mass overturning related to a reversal of the usual meridional θ gradient commonly observed in the occurrence of blocking type cold surge. Composite analyses based on the distribution of the WI and BI clearly demonstrate the dynamic evolutions of corresponding cold surge types. The wave-train cold surge is associated with a southeastward expansion of the Siberian High and northerly wind near surface, which is caused by growing baroclinic waves. During the blocking cold surge, a geopotential height dipole indicating the subarctic blocking and deepening of East Asian coastal trough induces a southward expansion of the Siberian High and northeasterly wind. Compared to the wave-train type, the blocking cold surge exhibits a longer duration and stronger intensity. In the new framework of these dynamic indices, we can detect a third type of cold surge when both the wave-train and the blocking occur together. In addition, we can exclude the events that do not have the essential features of the upper tropospheric disturbances or the subarctic anticyclonic circulation, which are responsible for cold surge occurrence, using the new indices.

21 CFR 520.2380a - Thiabendazole top dressing and mineral protein block.

Code of Federal Regulations, 2010 CFR

2010-04-01

... this section. (2) No. 050604 for use as in paragraph (e)(1)(ii) of this section. (3) No. 012286 for use... protein block feeding for 3 days. Milk taken from animals during treatment and within 96 hours (8 milkings... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Thiabendazole top dressing and mineral protein...

21 CFR 520.2380a - Thiabendazole top dressing and mineral protein block.

Code of Federal Regulations, 2014 CFR

2014-04-01

... this section. (2) No. 050604 for use as in paragraph (e)(1)(ii) of this section. (3) No. 012286 for use... protein block feeding for 3 days. Milk taken from animals during treatment and within 96 hours (8 milkings... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Thiabendazole top dressing and mineral protein...

21 CFR 520.2380a - Thiabendazole top dressing and mineral protein block.

Code of Federal Regulations, 2012 CFR

2012-04-01

... this section. (2) No. 050604 for use as in paragraph (e)(1)(ii) of this section. (3) No. 012286 for use... protein block feeding for 3 days. Milk taken from animals during treatment and within 96 hours (8 milkings... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Thiabendazole top dressing and mineral protein...

21 CFR 520.2380a - Thiabendazole top dressing and mineral protein block.

Code of Federal Regulations, 2013 CFR

2013-04-01

... this section. (2) No. 050604 for use as in paragraph (e)(1)(ii) of this section. (3) No. 012286 for use... protein block feeding for 3 days. Milk taken from animals during treatment and within 96 hours (8 milkings... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Thiabendazole top dressing and mineral protein...

21 CFR 520.2380a - Thiabendazole top dressing and mineral protein block.

Code of Federal Regulations, 2011 CFR

2011-04-01

... this section. (2) No. 050604 for use as in paragraph (e)(1)(ii) of this section. (3) No. 012286 for use... protein block feeding for 3 days. Milk taken from animals during treatment and within 96 hours (8 milkings... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Thiabendazole top dressing and mineral protein...

Myxobacterium-Produced Antibiotic TA (Myxovirescin) Inhibits Type II Signal Peptidase

PubMed Central

Xiao, Yao; Gerth, Klaus; Müller, Rolf

2012-01-01

Antibiotic TA is a macrocyclic secondary metabolite produced by myxobacteria that has broad-spectrum bactericidal activity. The structure of TA is unique, and its molecular target is unknown. Here, we sought to elucidate TA's mode of action (MOA) through two parallel genetic approaches. First, chromosomal Escherichia coli TA-resistant mutants were isolated. One mutant that showed specific resistance toward TA was mapped and resulted from an IS4 insertion in the lpp gene, which encodes an abundant outer membrane (Braun's) lipoprotein. In a second approach, the comprehensive E. coli ASKA plasmid library was screened for overexpressing clones that conferred TAr. This effort resulted in the isolation of the lspA gene, which encodes the type II signal peptidase that cleaves signal sequences from prolipoproteins. In whole cells, TA was shown to inhibit Lpp prolipoprotein processing, similar to the known LspA inhibitor globomycin. Based on genetic evidence and prior globomycin studies, a block in Lpp expression or prevention of Lpp covalent cell wall attachment confers TAr by alleviating a toxic buildup of mislocalized pro-Lpp. Taken together, these data argue that LspA is the molecular target of TA. Strikingly, the giant ta biosynthetic gene cluster encodes two lspA paralogs that we hypothesize play a role in producer strain resistance. PMID:22232277

Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

PubMed

Aoki, Hironori; Yamamoto, Eiichiro; Yamano, Hiro-O; Sugai, Tamotsu; Kimura, Tomoaki; Tanaka, Yoshihito; Matsushita, Hiro-O; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Nakaoka, Michiko; Yoshida, Yuko; Harada, Taku; Sudo, Gota; Eizuka, Makoto; Yorozu, Akira; Kitajima, Hiroshi; Niinuma, Takeshi; Kai, Masahiro; Nojima, Masanori; Suzuki, Hiromu; Nakase, Hiroshi

2018-03-15

Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, - 2, - 12, - 31, p16, and MLH1) were analyzed through pyrosequencing. Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

Blocking contacts for N-type cadmium zinc telluride

NASA Technical Reports Server (NTRS)

Stahle, Carl M. (Inventor); Parker, Bradford H. (Inventor); Babu, Sachidananda R. (Inventor)

2012-01-01

A process for applying blocking contacts on an n-type CdZnTe specimen includes cleaning the CdZnTe specimen; etching the CdZnTe specimen; chemically surface treating the CdZnTe specimen; and depositing blocking metal on at least one of a cathode surface and an anode surface of the CdZnTe specimen.

Tunable PhoXonic Band Gap Materials from Self-Assembly of Block Copoliymers and Colloidal Nanocrystals (NBIT Phase II)

DTIC Science & Technology

2011-05-06

electric fields. For that, we are going to use PS - b - P2VP block copolymers as a model system, utilizing the quite versatile chemistry of the P2VP ...displays. Our efforts at Hanyang have focused on tunable PBG materials self-assembled from polystyrene- b -poly(2-vinyl pyridine) ( PS - b - P2VP ) block...small angle x-ray scattering measurements during swelling of low molecular weight PS - P2VP polymers at the Cornell High Energy Synchrotron Source

Allogeneic substitution for nominal antigen-specific T-cell clone reactivity in schistosomiasis.

PubMed Central

Linette, G P; Lammie, P J; Phillips, S M

1986-01-01

The present studies have established the nature of a T-cell clone which demonstrates dual reactivity directed against Schistosoma mansoni antigen presented by syngeneic antigen presenting cells and against allogeneic cells. Clone G4, when stimulated by either antigen (SEA) or allogeneic cells (PL/J), exhibits similar functional and phenotypic characteristics. A subclone of G4, G4A.1, which has been maintained in continuous mixed lymphocyte culture for 12 months (in the absence of SEA), retains comparable reactivity with respect to proliferation and ability to produce lymphokines, transfer delayed-type hypersensitivity, and produce in vitro granulomas in response to SEA. Normal antigenic stimulation is highly contingent upon I-Ab compatibility while antibody blocking experiments map allo-reactivity to I-Eu. The failure of B10.PL spleen cells to stimulate G4, however, suggests that alloreactivity may be directed against the recently described Mls X locus. Both allogeneic and nominal antigen induced T-cell activation are blocked by antibody directed against L3T4A, confirming Class II MHC restriction for both types of stimulation. These studies suggest that stimulation of T cells by either alloantigen or nominal antigen elicits qualitatively similar functional profiles, and further suggest the feasibility of producing large numbers of nominal antigen reactive cloned T cells in the absence of nominal antigen under mixed lymphocyte culture conditions. PMID:2420707

Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells.

PubMed

Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

2009-08-01

Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA.

Sugar epitopes as potential universal disease transmission blocking targets.

PubMed

Dinglasan, Rhoel R; Valenzuela, Jesús G; Azad, Abdu F

2005-01-01

One promising method to prevent vector-borne diseases is through the use of transmission blocking vaccines (TBVs). However, developing several anti-pathogen TBVs may be impractical. In this study, we have identified a conserved candidate carbohydrate target in the midguts of several Arthropod vectors. A screen of the novel GlycoChip glycan array found that the anti-carbohydrate malaria transmission blocking monoclonal antibody (MG96) preferentially recognized D-mannose (alpha) and the type II lactosamine disaccharide. The specificity for D-mannose was confirmed by competition ELISA using alpha-methyl mannoside as inhibitor. Con A, which identifies terminal mannose residues, did not inhibit MG96 reactivity with mosquito midgut lysates, suggesting that Con A has differential recognition of this monosaccharide. However, the jack bean lectin, Jacalin, which recognizes D-mannose (alpha), d-galactose (alpha/beta) and the T antigen, not only displays a similar banding profile to that recognized by MG96 on immunoblot but was also shown to effectively inhibit MG96. Wheat-germ agglutinin, which recognizes N-acetyllactosamine units, only partially inhibited MG96 reactivity. This highlights the contribution of both glycan moieties to the MG96 epitope or glycotope. Enzyme deglycosylation results suggest that MG96 recognizes a mannose alpha1-6 substitution on an O-linked oligosaccharide. Taken together, the data suggest that MG96 recognizes a discontinuous glycotope composed of Manalpha1-6 proximal to Galbeta1-4GlcNAc-alpha-O-R glycans on arthropod vector midguts. As such, these glycotopes may represent potential transmission blocking vaccine targets for a wide range of vector-borne pathogens.

Functional Lateralization of Speech Processing in Adults and Children Who Stutter

PubMed Central

Sato, Yutaka; Mori, Koichi; Koizumi, Toshizo; Minagawa-Kawai, Yasuyo; Tanaka, Akihiro; Ozawa, Emi; Wakaba, Yoko; Mazuka, Reiko

2011-01-01

Developmental stuttering is a speech disorder in fluency characterized by repetitions, prolongations, and silent blocks, especially in the initial parts of utterances. Although their symptoms are motor related, people who stutter show abnormal patterns of cerebral hemispheric dominance in both anterior and posterior language areas. It is unknown whether the abnormal functional lateralization in the posterior language area starts during childhood or emerges as a consequence of many years of stuttering. In order to address this issue, we measured the lateralization of hemodynamic responses in the auditory cortex during auditory speech processing in adults and children who stutter, including preschoolers, with near-infrared spectroscopy. We used the analysis–resynthesis technique to prepare two types of stimuli: (i) a phonemic contrast embedded in Japanese spoken words (/itta/ vs. /itte/) and (ii) a prosodic contrast (/itta/ vs. /itta?/). In the baseline blocks, only /itta/ tokens were presented. In phonemic contrast blocks, /itta/ and /itte/ tokens were presented pseudo-randomly, and /itta/ and /itta?/ tokens in prosodic contrast blocks. In adults and children who do not stutter, there was a clear left-hemispheric advantage for the phonemic contrast compared to the prosodic contrast. Adults and children who stutter, however, showed no significant difference between the two stimulus conditions. A subject-by-subject analysis revealed that not a single subject who stutters showed a left advantage in the phonemic contrast over the prosodic contrast condition. These results indicate that the functional lateralization for auditory speech processing is in disarray among those who stutter, even at preschool age. These results shed light on the neural pathophysiology of developmental stuttering. PMID:21687442

Norepinephrine is coreleased with serotonin in mouse taste buds.

PubMed

Huang, Yijen A; Maruyama, Yutaka; Roper, Stephen D

2008-12-03

ATP and serotonin (5-HT) are neurotransmitters secreted from taste bud receptor (type II) and presynaptic (type III) cells, respectively. Norepinephrine (NE) has also been proposed to be a neurotransmitter or paracrine hormone in taste buds. Yet, to date, the specific stimulus for NE release in taste buds is not well understood, and the identity of the taste cells that secrete NE is not known. Chinese hamster ovary cells were transfected with alpha(1A) adrenoceptors and loaded with fura-2 ("biosensors") to detect NE secreted from isolated mouse taste buds and taste cells. Biosensors responded to low concentrations of NE (>or=10 nm) with a reliable fura-2 signal. NE biosensors did not respond to stimulation with KCl or taste compounds. However, we recorded robust responses from NE biosensors when they were positioned against mouse circumvallate taste buds and the taste buds were stimulated with KCl (50 mm) or a mixture of taste compounds (cycloheximide, 10 microm; saccharin, 2 mm; denatonium, 1 mm; SC45647, 100 microm). NE biosensor responses evoked by stimulating taste buds were reversibly blocked by prazosin, an alpha(1A) receptor antagonist. Together, these findings indicate that taste bud cells secrete NE when they are stimulated. We isolated individual taste bud cells to identify the origin of NE release. NE was secreted only from presynaptic (type III) taste cells and not receptor (type II) cells. Stimulus-evoked NE release depended on Ca(2+) in the bathing medium. Using dual biosensors (sensitive to 5-HT and NE), we found all presynaptic cells secrete 5-HT and 33% corelease NE with 5-HT.

Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2 receptor.

PubMed

Zhang, Shao-Ling; Moini, Babak; Ingelfinger, Julie R

2004-06-01

Although both the renin angiotensin system (RAS) and the paired homeobox 2 gene (Pax-2) seem critically important in renal organogenesis, whether and how they might interact has not been addressed. The present study asked whether a link between the RAS and Pax-2 exists in fetal renal cells, speculating that such an interaction, if present, might influence renal development. Embryonic kidney explants and embryonic renal cells (mouse late embryonic mesenchymal epithelial cells [MK4] and mouse early embryonic mesenchymal fibroblasts [MK3]) were used. Pax-2 protein and Pax-2 mRNA were detected by immunofluorescence, Western blot, reverse transcription-PCR, and real-time PCR. Angiotensin II (AngII) upregulated Pax-2 protein and Pax-2 mRNA expression via the AngII type 2 (AT(2)) receptor in MK4 but not in MK3 cells. The stimulatory effect of AngII on Pax-2 gene expression could be blocked by PD123319 (AT(2) inhibitor), AG 490 (a specific Janus kinase 2 inhibitor), and genistein (a tyrosine kinase inhibitor) but not by losartan (AT(1) inhibitor), SB203580 (specific p38 mitogen-activated protein kinase inhibitor), PD98059 (specific MEK inhibitor), SP600125 (JNK inhibitor), and diphenyleneiodonium chloride (an NADPH oxidase inhibitor). Moreover, embryonic kidney explants in culture confirmed that AngII upregulates Pax-2 gene expression via the AT(2) receptor. These studies demonstrate that the stimulatory effect of AngII on Pax-2 gene expression is mediated, at least in part, via the Janus kinase 2/signal transducers and activators of transcription signaling transduction pathway, suggesting that RAS and Pax-2 interactions may be important in renal development.

MHC Class II Activation and Interferon-γ Mediate the Inhibition of Neutrophils and Eosinophils by Staphylococcal Enterotoxin Type A (SEA).

PubMed

Ferreira-Duarte, Ana P; Pinheiro-Torres, Anelize S; Anhê, Gabriel F; Condino-Neto, Antônio; Antunes, Edson; DeSouza, Ivani A

2017-01-01

Staphylococcal enterotoxins are classified as superantigens that act by linking T-cell receptor with MHC class II molecules, which are expressed on classical antigen-presenting cells (APC). Evidence shows that MHC class II is also expressed in neutrophils and eosinophils. This study aimed to investigate the role of MHC class II and IFN-γ on chemotactic and adhesion properties of neutrophils and eosinophils after incubation with SEA. Bone marrow (BM) cells obtained from BALB/c mice were resuspended in culture medium, and incubated with SEA (3-30 ng/ml; 1-4 h), after which chemotaxis and adhesion were evaluated. Incubation with SEA significantly reduced the chemotactic and adhesive responses in BM neutrophils activated with IL-8 (200 ng/ml). Likewise, SEA significantly reduced the chemotactic and adhesive responses of BM eosinophils activated with eotaxin (300 ng/ml). The inhibitory effects of SEA on cell chemotaxis and adhesion were fully prevented by prior incubation with an anti-MHC class II blocking antibody (2 μg/ml). SEA also significantly reduced the intracellular Ca 2+ levels in IL-8- and eotaxin-activated BM cells. No alterations of MAC-1, VLA4, and LFA-1α expressions were observed after SEA incubation. In addition, SEA elevated by 3.5-fold ( P < 0.05) the INF-γ levels in BM cells. Incubation of BM leukocytes with IFN-γ (10 ng/ml, 2 h) reduced both neutrophil and eosinophil chemotaxis and adhesion, which were prevented by prior incubation with anti-MHC class II antibody (2 μg/ml). In conclusion, SEA inhibits neutrophil and eosinophil by MHC class II-dependent mechanism, which may be modulated by concomitant release of IFN-γ.

Chlorine-induced assembly of a cationic coordination cage with a μ5-carbonato-bridged Mn(II)24 core.

PubMed

Xiong, Ke-Cai; Jiang, Fei-Long; Gai, Yan-Li; Yuan, Da-Qiang; Han, Dong; Ma, Jie; Zhang, Shu-Quan; Hong, Mao-Chun

2012-04-27

Chlorine caged in! The chlorine-induced assembly of six shuttlecock-like tetranuclear Mn(II) building blocks generated in situ based on p-tert-butylthiacalix[4]arene and facial anions gave rise to a novel truncated distorted octahedral cationic coordination cage with a μ(5)-carbonato-bridged Mn(II)(24) core. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A role of nucleus accumbens dopamine receptors in the nucleus accumbens core, but not shell, in fear prediction error.

PubMed

Li, Susan S Y; McNally, Gavan P

2015-08-01

Two experiments used an associative blocking design to study the role of dopamine receptors in the nucleus accumbens shell (AcbSh) and core (AcbC) in fear prediction error. Rats in the experimental groups were trained to a visual fear-conditioned stimulus (conditional stimulus [CS]) A in Stage I, whereas rats in the control groups were not. In Stage II, all rats received compound fear conditioning of the visual CSA and an auditory CSB. Rats were later tested for their fear responses to CSB. All rats received microinjections of saline or the D1-D2 receptor antagonist cis-(z)-flupenthixol prior to Stage II. These microinjections targeted either the AcbSh (Experiment 1) or the AcbC (Experiment 2). In each experiment, Stage I fear conditioning of CSA blocked fear learning to CSB. Microinjection of cis-(z)-flupenthixol (10 or 20 μg) into the AcbSh (Experiment 1) had no effect on fear learning or associative blocking. In contrast, microinjection of cis-(z)-flupenthixol (10 or 20 μg) into the AcbC (Experiment 2) attenuated blocking and so enabled fear learning to CSB. These results identify the AcbC as the critical locus for dopamine receptor contributions to fear prediction error and the associative blocking of fear learning. (c) 2015 APA, all rights reserved).

Stain susceptibility of composite and ceramic CAD/CAM blocks versus direct resin composites with different resinous matrices.

PubMed

Alharbi, Amal; Ardu, Stefano; Bortolotto, Tissiana; Krejci, Ivo

2017-04-01

To evaluate the stain susceptibility of CAD/CAM blocks and direct composite after long term exposure to various staining agents. 40 disk-shaped samples were fabricated from each of nine materials; six CAD/CAM (Vitablocs Mark II, Paradigm MZ100, Experimental Vita Hybrid Ceramic, Vita Enamic, Experimental Kerr and Lava Ultimate) and three direct composites (Filtek Supreme, Venus Diamond and Filtek Silorane). Samples were randomly divided into five groups (n = 8) according to different staining solutions (distilled water, tea, red wine, coffee and artificial saliva). Initial L*a*b* values were assessed using a calibrated digital spectrophotometer. Specimens were immersed in staining solutions and stored in an incubator at 37 °C for 120 days. L*a*b* values were assessed again and color change (∆E) was calculated as difference between recorded L*a*b* values. ANOVA, and Duncan test were used to identify differences between groups (α = 0.05). Significant differences in ∆E values were detected between materials (p = 0.000). Among all staining solutions, the highest ∆E value was observed with red wine. The new CAD/CAM blocks (Vita Enamic, Vita Hybrid Ceramic and Lava Ultimate) showed the highest resistance to staining compared to the MZ100 composite resin blocks. Filtek Silorane, a direct composite, showed high stain resistance values compared to CAD/CAM materials and other direct composites. Ceramic and composite CAD/CAM blocks had lower staining susceptibility than methacrylate based direct composite. Staining susceptibility of the new resin based CAD/CAM materials Vita Enamic and Lava Ultimate was comparable to feldspathic ceramic blocks (Vitablocs Mark II). Filtek Silorane showed promising results that were comparable to some CAD/CAM blocks.

Class I HDACs Regulate Angiotensin II-Dependent Cardiac Fibrosis via Fibroblasts and Circulating Fibrocytes

PubMed Central

Williams, Sarah M.; Golden-Mason, Lucy; Ferguson, Bradley S.; Douglas, Katherine B.; Cavasin, Maria A.; Demos-Davies, Kim; Yeager, Michael E.; Stenmark, Kurt R.; McKinsey, Timothy A.

2014-01-01

Fibrosis, which is defined as excessive accumulation of fibrous connective tissue, contributes to the pathogenesis of numerous diseases involving diverse organ systems. Cardiac fibrosis predisposes individuals to myocardial ischemia, arrhythmias and sudden death, and is commonly associated with diastolic dysfunction. Histone deacetylase (HDAC) inhibitors block cardiac fibrosis in pre-clinical models of heart failure. However, which HDAC isoforms govern cardiac fibrosis, and the mechanisms by which they do so, remains unclear. Here, we show that selective inhibition of class I HDACs potently suppresses angiotensin II (Ang II)-mediated cardiac fibrosis by targeting two key effector cell populations, cardiac fibroblasts and bone marrow-derived fibrocytes. Class I HDAC inhibition blocks cardiac fibroblast cell cycle progression through derepression of the genes encoding the cyclin-dependent kinase (CDK) inhibitors, p15 and p57. In contrast, class I HDAC inhibitors block agonist-dependent differentiation of fibrocytes through a mechanism involving repression of ERK1/2 signaling. These findings define novel roles for class I HDACs in the control of pathological cardiac fibrosis. Furthermore, since fibrocytes have been implicated in the pathogenesis of a variety of human diseases, including heart, lung and kidney failure, our results suggest broad utility for isoform-selective HDAC inhibitors as anti-fibrotic agents that function, in part, by targeting these circulating mesenchymal cells. PMID:24374140

The effect of iron to manganese substitution on microperoxidase 8 catalysed peroxidase and cytochrome P450 type of catalysis.

PubMed

Primus, J L; Boersma, M G; Mandon, D; Boeren, S; Veeger, C; Weiss, R; Rietjens, I M

1999-06-01

This study describes the catalytic properties of manganese microperoxidase 8 [Mn(III)MP8] compared to iron microperoxidase 8 [Fe(III)MP8]. The mini-enzymes were tested for pH-dependent activity and operational stability in peroxidase-type conversions, using 2-methoxyphenol and 3,3'-dimethoxybenzidine, and in a cytochrome P450-like oxygen transfer reaction converting aniline to para-aminophenol. For the peroxidase type of conversions the Fe to Mn replacement resulted in a less than 10-fold decrease in the activity at optimal pH, whereas the aniline para-hydroxylation is reduced at least 30-fold. In addition it was observed that the peroxidase type of conversions are all fully blocked by ascorbate and that aniline para-hydroxylation by Fe(III)MP8 is increased by ascorbate whereas aniline para-hydroxylation by Mn(III)MP8 is inhibited by ascorbate. Altogether these results indicate that different types of reactive metal oxygen intermediates are involved in the various conversions. Compound I/II, scavenged by ascorbate, may be the reactive species responsible for the peroxidase reactions, the polymerization of aniline and (part of) the oxygen transfer to aniline in the absence of ascorbate. The para-hydroxylation of aniline by Fe(III)MP8, in the presence of ascorbate, must be mediated by another reactive iron-oxo species which could be the electrophilic metal(III) hydroperoxide anion of microperoxidase 8 [M(III)OOH MP8]. The lower oxidative potential of Mn, compared to Fe, may affect the reactivity of both compound I/II and the metal(III) hydroperoxide anion intermediate, explaining the differential effect of the Fe to Mn substitution on the pH-dependent behavior, the rate of catalysis and the operational stability of MP8.

Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.

PubMed

Jones, Keith T

2008-01-01

Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV), dictyate stage of prophase I and at metaphase II. These arrests are spanned by three key events, the focus of this review: (i) passage from mitosis to GV arrest during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and (iii) completion of meiosis II following fertilization, both meiotic divisions being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human oocytes is associated with an age-related high rate of chromosomal mis-segregation, such as trisomy 21 (Down's syndrome), resulting in aneuploid conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a consequence of an age-long decline in the cohesive ties holding chromosomes together. Such loss goes undetected by the oocyte during meiosis I either because its ability to respond and block division also deteriorates with age, or as a consequence of being inherently unable to respond to the types of segregation defects induced by cohesion loss.

Mimicry by asx- and ST-turns of the four main types of beta-turn in proteins.

PubMed

Duddy, William J; Nissink, J Willem M; Allen, Frank H; Milner-White, E James

2004-11-01

Hydrogen-bonded beta-turns in proteins occur in four categories: type I (the most common), type II, type II', and type I'. Asx-turns resemble beta-turns, in that both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and threonine side chains also commonly form hydrogen-bonded turns, here called ST-turns. Asx-turns and ST-turns can be categorized into four classes, based on side chain rotamers and the conformation of the central turn residue, which are geometrically equivalent to the four types of beta-turns. We propose asx- and ST-turns be named using the type I, II, I', and II' beta-turn nomenclature. Using this, the frequency of occurrence of both asx- and ST-turns is: type II' > type I > type II > type I', whereas for beta-turns it is type I > type II > type I' > type II'. Almost all type II asx-turns occur as a recently described three residue feature named an asx-nest.

Prophase I Mouse Oocytes Are Deficient in the Ability to Respond to Fertilization by Decreasing Membrane Receptivity to Sperm and Establishing a Membrane Block to Polyspermy1

PubMed Central

Kryzak, Cassie A.; Moraine, Maia M.; Kyle, Diane D.; Lee, Hyo J.; Cubeñas-Potts, Caelin; Robinson, Douglas N.; Evans, Janice P.

2013-01-01

ABSTRACT Changes occurring as the prophase I oocyte matures to metaphase II are critical for the acquisition of competence for normal egg activation and early embryogenesis. A prophase I oocyte cannot respond to a fertilizing sperm as a metaphase II egg does, including the ability to prevent polyspermic fertilization. Studies here demonstrate that the competence for the membrane block to polyspermy is deficient in prophase I mouse oocytes. In vitro fertilization experiments using identical insemination conditions result in monospermy in 87% of zona pellucida (ZP)-free metaphase II eggs, while 92% of ZP-free prophase I oocytes have four or more fused sperm. The membrane block is associated with a postfertilization reduction in the capacity to support sperm binding, but this reduction in sperm-binding capacity is both less robust and slower to develop in fertilized prophase I oocytes. Fertilization of oocytes is dependent on the tetraspanin CD9, but little to no release of CD9 from the oocyte membrane is detected, suggesting that release of CD9-containing vesicles is not essential for fertilization. The deficiency in membrane block establishment in prophase I oocytes correlates with abnormalities in two postfertilization cytoskeletal changes: sperm-induced cortical remodeling that results in fertilization cone formation and a postfertilization increase in effective cortical tension. These data indicate that cortical maturation is a component of cytoplasmic maturation during the oocyte-to-egg transition and that the egg cortex has to be appropriately primed and tuned to be responsive to a fertilizing sperm. PMID:23863404

Inhibitory effect of PRO 2000, a candidate microbicide, on dendritic cell-mediated human immunodeficiency virus transfer.

PubMed

Teleshova, Natalia; Chang, Theresa; Profy, Albert; Klotman, Mary E

2008-05-01

Without an effective vaccine against human immunodeficiency virus (HIV) infection, topical microbicide development has become a priority. The sulfonated polyanion PRO 2000, a candidate topical microbicide now in phase II/III clinical trials, blocks HIV infection of cervical tissue in vitro. Dendritic cells (DC) are among the first cell types to contact HIV in the genital tract and facilitate the spread of the virus. Thus, interfering with virus-DC interactions is a desirable characteristic of topical microbicides as long as that does not interfere with the normal function of DC. PRO 2000 present during capture of the replication-defective HIV(JRFL) reporter virus or replication-competent HIV(BaL) by monocyte-derived DC (MDDC) inhibited subsequent HIV transfer to target cells. Continuous exposure to PRO 2000 during MDDC-target cell coculture effectively inhibited HIV infection of target cells. PRO 2000 inhibited HIV capture by MDDC. In addition, the compound blocked R5 and X4 HIV envelope-mediated cell-cell fusion. Interestingly, simultaneous exposure to PRO 2000 and lipopolysaccharide attenuated the cytokine production in response to stimulation, suggesting that the compound altered DC function. While efficient blocking of MDDC-mediated virus transfer and infection in the highly permissive MDDC-T-cell environment reinforces the potential value of PRO 2000 as a topical microbicide against HIV, the impact of PRO 2000 on immune cell functions warrants careful evaluation.

Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921

PubMed Central

Pugsley, Michael K; Goldin, Alan L

1999-01-01

RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp.RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 μM, whereas the EC50 for block of the IFMQ3 mutant channel was 110±5.5 μM.Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels.RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms.Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with kon equal to 0.11±0.012×106 M−1 s−1 and koff equal to 12.5±2.5 s−1, resulting in KD of 117±31 μM. Recovery from open channel block occurred with a time constant of 14±2.7 s−1.These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia. PMID:10369450

Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921.

PubMed

Pugsley, M K; Goldin, A L

1999-05-01

RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp. RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 microM, whereas the EC50 for block of the IFMQ3 mutant channel was 110+5.5 microM. Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels. RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms. Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with k(on) equal to 0.11+/-0.012x10(6) M(-1) s(-1) and k(off) equal to 12.5+/-2.5 s(-1), resulting in KD of 117+/-31 microM. Recovery from open channel block occurred with a time constant of 14+/-2.7 s(-1). These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia.

A novel design of combining the angiotensin converting enzyme (ACE) inhibitor captopril with the angiotensin receptor blocker (ARB) losartan using homo coupling via PEG diacid linker.

PubMed

Hashemzadeh, Mehrnoosh; Park, Shery; Ju, Hee; Movahed, Mohammad R

2013-12-01

Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting Enzyme (ACE) inhibitors prevent the production of angiotensin II, which has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. ARBs have been shown to be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to design and discuss the benefits of a new molecule, which combines captopril, an ACE inhibitor, with losartan, an ARB. In this experiment Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system by blocking the effect of angiotensin II they have different action sites and mechanisms some patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on endothelial and smooth muscle cells.

The Herpes Simplex Virus Type 1 Latency-Associated Transcript Can Protect Neuron-Derived C1300 and Neuro2A Cells from Granzyme B-Induced Apoptosis and CD8 T-Cell Killing▿

PubMed Central

Jiang, Xianzhi; Alami Chentoufi, Aziz; Hsiang, Chinhui; Carpenter, Dale; Osorio, Nelson; BenMohamed, Lbachir; Fraser, Nigel W.; Jones, Clinton; Wechsler, Steven L.

2011-01-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is the only HSV-1 gene transcript abundantly expressed throughout latency. LAT null mutants have a significantly reduced reactivation phenotype. LAT's antiapoptosis activity is the major LAT factor involved in supporting the wild-type reactivation phenotype. During HSV-1 latency, some ganglionic neurons are surrounded by CD8 T cells, and it has been proposed that these CD8 T cells help maintain HSV-1 latency by suppressing viral reactivations. Surprisingly, despite injection of cytotoxic lytic granules by these CD8 T cells into latently infected neurons, neither apoptosis nor neuronal cell death appears to occur. We hypothesized that protection of latently infected neurons against cytotoxic CD8 T-cell killing is due to LAT's antiapoptosis activity. Since CD8 T-cell cytotoxic lytic granule-mediated apoptosis is critically dependent on granzyme B (GrB), we examined LAT's ability to block GrB-induced apoptosis. We report here that (i) LAT can interfere with GrB-induced apoptosis in cell cultures, (ii) LAT can block GrB-induced cleavage (activation) of caspase-3 both in cell culture and in a cell-free in vitro cell extract assay, and (iii) LAT can protect C1300 and Neuro2A cells from cytotoxic CD8 T-cell killing in vitro. These findings support the hypothesis that LAT's antiapoptosis activity can protect latently infected neurons from being killed by CD8 T-cell lytic granules in vivo. PMID:21177822

A magnetostructural study of linear NiII MnIII NiII, NiII CrIII NiII and triangular Ni(II)3 species containing (pyridine-2-aldoximato)nickel(II) unit as a building block.

PubMed

Weyhermüller, Thomas; Wagner, Rita; Khanra, Sumit; Chaudhuri, Phalguni

2005-08-07

Three trinuclear complexes, NiII MnIII NiII, NiII CrIII NiII and Ni(II)3 based on (pyridine-2-aldoximato)nickel(II) units are described. Two of them, and , contain metal-centers in linear arrangement, as is revealed by X-ray diffraction. Complex is a homonuclear complex in which the three nickel(II) centers are disposed in a triangular fashion. The compounds were characterized by various physical methods including cyclic voltammetric and variable-temperature (2-290 K) susceptibility measurements. Complexes and display antiferromagnetic exchange coupling of the neighbouring metal centers, while weak ferromagnetic spin exchange between the adjacent Ni II and Cr III ions in is observed. The experimental magnetic data were simulated by using appropriate models.

A drift experiment to assess the influence of wind on recovery of oiled seabirds on St Paul Island, Alaska

USGS Publications Warehouse

Flint, Paul L.; Fowler, A.C.

1998-01-01

We used wooden blocks to estimate the proportion of oiled seabird carcasses that were likely to be recovered on beaches of St Paul Island, Alaska following a near-shore oil spill. We released a total of 302 blocks 6 km north of the island in 1997 at the site of a 17 II 1996 oil spill. We used a paired design and released half the blocks when the winds were onshore and released the second half when the winds were offshore. We systematically searched beaches after the second release to recover blocks. We recovered 93 of 152 (61%) blocks released when winds were onshore but only 1 of 150 (0.7%) blocks released when winds were offshore. Given that winds following the 1996 spill were offshore, we conclude that most birds killed at sea following the 1996 spill were likely not recovered on beaches.

[Construction of porous hydroxyapatite (HA) block loaded with cultured chondrocytes].

PubMed

Yan, M; Dang, G

1999-07-01

To construct a kind of bone healing enhancing implant with cultured chondrocytes bound to hydroxyapatite (HA). Chondrocytes were obtained from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x 3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was taken to show whether the cells grew outside and inside the pore of HA block. The cells cultured on tiny glass sheet for 2 days were used to prove where the cells come from by in situ hybridization technique with alpha1 (II) cDNA probe. Scanning electron micrographs showed that the pores of the HA surface and inside of the blocks are filled with cultured cells, especially the longer cultured block. The cells were chondrocytes confirmed by in situ hybridization. The porous HA can be used as cell cultured substrate and chondrocyte can adhere and proliferate inside the porous HA block.

Poly(cyclohexylethylene)- block-poly(ethylene oxide) block polymers for metal oxide templating

DOE PAGES

Schulze, Morgan W.; Sinturel, Christophe; Hillmyer, Marc A.

2015-09-01

A series of poly(cyclohexylethylene)- block-poly(ethylene oxide) (CEO) diblock copolymers were synthesized through tandem anionic polymerizations and heterogeneous catalytic hydrogenation. Solvent-annealed CEO diblock films were used to template dense arrays of inorganic oxide nanodots via simple spin coating of an inorganic precursor solution atop the ordered film. The substantial chemical dissimilarity of the two blocks enables (i) selective inclusion of the inorganic precursor within the PEO domain and (ii) the formation of exceptionally small feature sizes due to a relatively large interaction parameter estimated from mean-field analysis of the order–disorder transition temperatures of compositionally symmetric samples. UV/ozone treatment following incorporation producesmore » an ordered arrangement of oxide nanodots and simultaneously removes the block polymer template. However, we report the smallest particles (6 ± 1 nm) templated from a selective precursor insertion method to date using a block polymer scaffold.« less

Mannostatin A, a new glycoprotein-processing inhibitor.

PubMed

Tropea, J E; Kaushal, G P; Pastuszak, I; Mitchell, M; Aoyagi, T; Molyneux, R J; Elbein, A D

1990-10-30

Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal alpha-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward alpha- and beta-glucosidase and galactosidase as well as beta-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal alpha-mannosidases, with estimated IC50's of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC50 of about 10-15 nM with p-nitrophenyl alpha-D-mannopyranoside as substrate, and about 90 nM with [3H]mannose-labeled GlcNAc-Man5GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate that the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity.

Superconductivity in REO0.5F0.5BiS2 with high-entropy-alloy-type blocking layers

NASA Astrophysics Data System (ADS)

Sogabe, Ryota; Goto, Yosuke; Mizuguchi, Yoshikazu

2018-05-01

We synthesized new REO0.5F0.5BiS2 (RE: rare earth) superconductors with high-entropy-alloy-type (HEA-type) REO blocking layers. The lattice constant a systematically changed in the HEA-type samples with the RE concentration and the RE ionic radius. A sharp superconducting transition was observed in the resistivity measurements for all the HEA-type samples, and the transition temperature of the HEA-type samples was higher than that of typical REO0.5F0.5BiS2. The sharp superconducting transition and the enhanced superconducting properties of the HEA-type samples may indicate the effectiveness of the HEA states of the REO blocking layers in the REO0.5F0.5BiS2 system.

EGF receptor-targeting peptide conjugate incorporating a near-IR fluorescent dye and a novel 1,4,7-triazacyclononane-based (64)Cu(II) chelator assembled via click chemistry.

PubMed

Viehweger, Katrin; Barbaro, Lisa; García, Karina Pombo; Joshi, Tanmaya; Geipel, Gerhard; Steinbach, Jörg; Stephan, Holger; Spiccia, Leone; Graham, Bim

2014-05-21

A new Boc-protected 1,4,7-triazacyclononane (TACN)-based pro-chelator compound featuring a "clickable" azidomethylpyridine pendant has been developed as a building block for the construction of multimodal imaging agents. Conjugation to a model alkyne (propargyl alcohol), followed by deprotection, generates a pentadentate ligand, as confirmed by X-ray crystallographic analysis of the corresponding distorted square-pyramidal Cu(II) complex. The ligand exhibits rapid (64)Cu(II)-binding kinetics (>95% radiochemical yield in <5 min) and a high resistance to demetalation. It may thus prove suitable for use in (64)Cu(II)-based in vivo positron emission tomography (PET). The new chelating building block has been applied to the construction of a bimodal (PET/fluorescence) peptide-based imaging probe targeting the epidermal growth factor (EGF) receptor, which is highly overexpressed on the surface of several types of cancer cells. The probe consists of a hexapeptide sequence, Leu-Ala-Arg-Leu-Leu-Thr (designated "D4"), followed by a Cys-β-Ala-β-Ala spacer, then a β-homopropargylglycine residue with the TACN-based chelator "clicked" to its side chain. A sulfonated near-infrared (NIR) fluorescent cyanine dye (sulfo-Cy5) was introduced at the N-terminus to study the EGF receptor-binding ability of the probe by laser-fluorescence spectroscopy. Binding was also confirmed by coimmunoprecipitation methods, and an apparent dissociation constant (Kd) of ca. 10 nM was determined from radioactivity-based measurements of probe binding to two EGF receptor-expressing cell lines (FaDu and A431). The probe is shown to be a biased or partial allosteric agonist of the EGF receptor, inducing phosphorylation of Thr669 and Tyr992, but not the Tyr845, Tyr998, Tyr1045, Tyr1068, or Tyr1148 residues of the receptor, in the absence of the orthosteric EGF ligand. Additionally, the probe was found to suppress the EGF-stimulated autophosphorylation of these latter residues, indicating that it is also a noncompetitive antagonist.

Dual shell-like magnetic clusters containing Ni(II) and Ln(III) (Ln = La, Pr, and Nd) ions.

PubMed

Kong, Xiang-Jian; Ren, Yan-Ping; Long, La-Sheng; Zheng, Zhiping; Nichol, Gary; Huang, Rong-Bin; Zheng, Lan-Sun

2008-04-07

Dual shell-like nanoscopic magnetic clusters featuring a polynuclear nickel(II) framework encapsulating that of lanthanide ions (Ln = La, Pr, and Nd) were synthesized using Ni(NO3)(2).6H2O, Ln(NO3)(3).6H2O, and iminodiacetic acid (IDA) under hydrothermal conditions. Structurally established by crystallographic studies, these clusters are [La20Ni30(IDA)30(CO3)6(NO3)6(OH)30(H2O)12](CO3)(6).72H2O (1), [Ln20Ni21(C4H5NO4)21(OH)24(C2H2O3)6(C2O4)3(NO3)9(H2O)12](NO3)9.nH2O [C2H2O3 is the alkoxide form of glycolate; Ln = Pr (2), n = 42; Nd (3), n = 50], and {[La4Ni5Na(IDA)5(CO3)(NO3)4(OH)5(H2O)5][CO3].10H2O} infinity (4). Carbonate, oxalate, and glycolate are products of hydrothermal decomposition of IDA. Compositions of these compounds were confirmed by satisfactory elemental analyses. It has been found that the cluster structure is dependent on the identity of the lanthanide ion as well as the starting Ln/Ni/IDA ratio. The cationic cluster of 1 features a core of the Keplerate type with an outer icosidodecahedron of Ni(II) ions encaging a dodecahedral kernel of La(III). Clusters 2 and 3, distinctly different from 1, are isostructural, possessing a core of an outer shell of 21 Ni(II) ions encapsulating an inner shell of 20 Ln(III) ions. Complex 4 is a three-dimensional assembly of cluster building blocks connected by units of Na(NO3)/La(NO3)3; the structure of the building block resembles closely that of 1, with a hydrated La(III) ion internalized in the decanuclear cage being an extra feature. Magnetic studies indicated ferromagnetic interactions in 1, while overall antiferromagnetic interactions were revealed for 2 and 3. The polymeric, three-dimensional cluster network 4 displayed interesting ferrimagnetic interactions.

Management of lumbar zygapophysial (facet) joint pain

PubMed Central

Manchikanti, Laxmaiah; Hirsch, Joshua A; Falco, Frank JE; Boswell, Mark V

2016-01-01

AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back pain. METHODS: The review process applied systematic evidence-based assessment methodology of controlled trials of diagnostic validity and randomized controlled trials of therapeutic efficacy. Inclusion criteria encompassed all facet joint interventions performed in a controlled fashion. The pain relief of greater than 50% was the outcome measure for diagnostic accuracy assessment of the controlled studies with ability to perform previously painful movements, whereas, for randomized controlled therapeutic efficacy studies, the primary outcome was significant pain relief and the secondary outcome was a positive change in functional status. For the inclusion of the diagnostic controlled studies, all studies must have utilized either placebo controlled facet joint blocks or comparative local anesthetic blocks. In assessing therapeutic interventions, short-term and long-term reliefs were defined as either up to 6 mo or greater than 6 mo of relief. The literature search was extensive utilizing various types of electronic search media including PubMed from 1966 onwards, Cochrane library, National Guideline Clearinghouse, clinicaltrials.gov, along with other sources including previous systematic reviews, non-indexed journals, and abstracts until March 2015. Each manuscript included in the assessment was assessed for methodologic quality or risk of bias assessment utilizing the Quality Appraisal of Reliability Studies checklist for diagnostic interventions, and Cochrane review criteria and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment tool for therapeutic interventions. Evidence based on the review of the systematic assessment of controlled studies was graded utilizing a modified schema of qualitative evidence with best evidence synthesis, variable from level I to level V. RESULTS: Across all databases, 16 high quality diagnostic accuracy studies were identified. In addition, multiple studies assessed the influence of multiple factors on diagnostic validity. In contrast to diagnostic validity studies, therapeutic efficacy trials were limited to a total of 14 randomized controlled trials, assessing the efficacy of intraarticular injections, facet or zygapophysial joint nerve blocks, and radiofrequency neurotomy of the innervation of the facet joints. The evidence for the diagnostic validity of lumbar facet joint nerve blocks with at least 75% pain relief with ability to perform previously painful movements was level I, based on a range of level I to V derived from a best evidence synthesis. For therapeutic interventions, the evidence was variable from level II to III, with level II evidence for lumbar facet joint nerve blocks and radiofrequency neurotomy for long-term improvement (greater than 6 mo), and level III evidence for lumbosacral zygapophysial joint injections for short-term improvement only. CONCLUSION: This review provides significant evidence for the diagnostic validity of facet joint nerve blocks, and moderate evidence for therapeutic radiofrequency neurotomy and therapeutic facet joint nerve blocks in managing chronic low back pain. PMID:27190760

40 CFR Table 3 to Subpart Qqqq of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2011 CFR

2011-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4767(a) i. Collecting the combustion temperature data according to § 63.4768(c);ii. Reducing the data to 3-hour block averages; and iii. Maintaining the 3-hour block average combustion...

40 CFR Table 3 to Subpart Qqqq of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2010 CFR

2010-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4767(a) i. Collecting the combustion temperature data according to § 63.4768(c);ii. Reducing the data to 3-hour block averages; and iii. Maintaining the 3-hour block average combustion...

Characteristics of ten tropical hardwoods from certified forests in Bolivia. Part II, Natural durability to decay fungi

Treesearch

Regis B. Miller; Alex C. Wiedenhoeft; R. Sam Williams; Willy Stockman; Frederick Green

2003-01-01

The natural durability of 10 lesser known, commercially available Bolivian hardwoods to decay fungi was evaluated using a modified ASTM soil-block analysis for 12 weeks. The blocks were then retested for an additional 12 weeks to determine their level of decay resistance, as determined by percentage of weight loss. Astronium urundeuva, Caesalpinia cf. pluviosa,...

Mode Medium Interaction. A Theoretical Study.

DTIC Science & Technology

1980-09-01

Report) 10. SUPPLEMENTARY NOTES I9. KEY WORDS (Conrlfnue on reverse side II necessary mnd Identify by block rumber) CO, Laser Transfer Function...Chemical Laser Unstable Resonator Brillouin Scattering Instability Supersonic Laser Modes Acoustic Noise Acoustic Instability Perturbed Resonator Gain...end Identify by block number) An instability in the output of a high-power unstable-resonator cw CO2 laser is analyzed in terms of the perturbative

s-Block Elements. Independent Learning Project for Advanced Chemistry (ILPAC). Unit I1.

ERIC Educational Resources Information Center

Inner London Education Authority (England).

This unit is one of 10 first year units produced by the Independent Learning Project for Advanced Chemistry (ILPAC). The unit, which consists of two sections and an appendix, focuses on the elements and compounds of Groups I and II (the s-block) of the periodic table. The groups are treated concurrently to note comparisons between groups and to…

BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents.

PubMed

Huys, Isabelle; Xu, Chen-Qi; Wang, Cheng-Zhong; Vacher, Hélène; Martin-Eauclaire, Marie-France; Chi, Cheng-Wu; Tytgat, Jan

2004-03-15

A novel HERG channel blocker was isolated from the venom of the scorpion Buthus martensi Karsch, sequenced and characterized at the pharmacological level after chemical synthesis. According to the determined amino acid sequence, the cDNA and genomic genes were then cloned. The genomic gene consists of two exons interrupted by an intron of 65 bp at position -6 upstream from the mature toxin. The protein sequence of this toxin was completely identical with that of a known A-type K+ current blocker BmTx3, belonging to scorpion alpha-KTx subfamily 15. Thus BmTx3 is the first reported alpha-KTx peptide also showing HERG-blocking activity, like gamma-KTx peptides. Moreover, different from classical alpha-KTx peptides, such as charybdotoxin, BmTx3 cannot block Shaker -type K+ channels. Phylogenetic tree analysis reveals that this toxin takes an intermediate position between classical alpha-KTx and gamma-KTx toxins. From a structural point of view, we propose that two separate functional faces might exist on the BmTx3 molecule, responsible for the two different K+-current-blocking functions. Face A, composed of Arg18 and Lys19 in the alpha-helix side, might correspond to HERG blocking activity, whereas Face B, containing a putative functional dyad (Lys27 and Tyr36) in the beta-sheet side, might correspond to A-type blocking activity. A specific deletion mutant with the disrupted Face B, BmTx3-Y36P37del, loses the A-type current-blocking activity, but keeps a similar HERG-blocking activity, as seen with the wild-type toxin.

Toothbrushing alters the surface roughness and gloss of composite resin CAD/CAM blocks.

PubMed

Kamonkhantikul, Krid; Arksornnukit, Mansuang; Lauvahutanon, Sasipin; Takahashi, Hidekazu

2016-01-01

This study investigated the surface roughness and gloss of composite resin CAD/CAM blocks after toothbrushing. Five composite resin blocks (Block HC, Cerasmart, Gradia Block, KZR-CAD Hybrid Resin Block, and Lava Ultimate), one hybrid ceramic (Vita Enamic), one feldspar ceramic (Vitablocs Mark II), one PMMA block (Telio CAD), and one conventional composite resin (Filtek Z350 XT) were evaluated. Surface roughness (Ra) and gloss were determined for each group of materials (n=6) after silicon carbide paper (P4000) grinding, 10k, 20k, and 40k toothbrushing cycles. One-way repeated measures ANOVA indicated significant differences in the Ra and gloss of each material except for the Ra of GRA. After 40k toothbrushing cycles, the Ra of BLO and TEL showed significant increases, while CER, KZR, ULT, and Z350 showed significant decreases. GRA, ENA, and VIT maintained their Ra. All of the materials tested, except CER, demonstrated significant decreases in gloss after 40k toothbrushing cycles.

An alternative method for sampling and petrographically characterizing an Eocene coal bed, southeast Kalimantan, Indonesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, T.A.

1990-01-01

A study undertaken on an Eocene age coal bed in southeast Kalimantan, Indonesia determined that there was a relationship between megascopically determined coal types and kinds and sizes of organic components. The study also concluded that the most efficient way to characterize the seam was from collection of two 3 cm blocks from each layer or bench defined by megascopic character and that a maximum of 125 point counts was needed on each block. Microscopic examination of uncrushed block samples showed the coal to be composed of plant parts and tissues set in a matrix of both fine-grained and amorphousmore » material. The particulate matrix is composed of cell wall and liptinite fragments, resins, spores, algae, and fungal material. The amorphous matrix consists of unstructured (at 400x) huminite and liptinite. Size measurements showed that each particulate component possessed its own size distribution which approached normality when transformed to a log{sub 2} or phi scale. Degradation of the plant material during peat accumulation probably controlled grain size in the coal types. This notion is further supported by the increased concentration of decay resistant resin and cell fillings in the nonbanded and dull coal types. In the sampling design experiment, two blocks from each layer and two layers from each coal type were collected. On each block, 2 to 4 traverses totaling 500 point counts per block were performed to test the minimum number of points needed to characterize a block. A hierarchical analysis of variance showed that most of the petrographic variation occurred between coal types. The results from these analyses also indicated that, within a coal type, sampling should concentrate on the layer level and that only 250 point counts, split between two blocks, were needed to characterize a layer.« less

MX Siting Investigation. Geotechnical Evaluation. Volume V. Nevada - Utah Verification Studies, FY 79. Geotechnical Data White River North CDP, Nevada.

DTIC Science & Technology

1979-08-24

5 . TYPE OF REPORT 0 PERIOD COVERED L’-, P.eRORMCG- 0 i. PERFORMING ORG. REPORT t...34 0 / AJ " " 20. ABSTRACT (Continue on reverse side It necesry and identify by block umberj hI-)? , --c. r ’ & 5 iI"’ Ia’A L_ q- ..>- 4c r, 5 - -41 ac...8217 241 291 Ill Ill 11 11 11 Ill It, T:-1: 11 1: ;, s2 2 L I I 1 5 I.L cc. a. is I.. :I 3 ’ S 0 5 2 2 1 󈧩 2 2 1 *1 -I %V44 3 IA &it 045 00 19 055

Cortex content of asporogenous mutants of Bacillus subtilis.

PubMed Central

Imae, Y; Strominger, J L

1976-01-01

A method for the measurement of muramic lactam, which is specifically located in the cortical peptidoglycan of bacterial spores, was developed as a quantitative assay method for spore cortex content. During sporulation of Bacillus subtilis 168, muramic lactam (i.e., spore cortex) began to appear at state IV of sporulation and continued to increase over most of the late stages of sporulation. Spore cortex contents of various spo mutants of B. subitils were surveyed. Cortex was not detected in mutants in which sporulation was blocked earlier than stage II sporulation. Spores of spo IV mutant had about 40% of the cortex content of the wild-type spores. One spo III mutant had a low amount of cortex, but four others had none. PMID:1262319

RGS2 is regulated by angiotensin II and functions as a negative feedback of aldosterone production in H295R human adrenocortical cells.

PubMed

Romero, Damian G; Plonczynski, Maria W; Gomez-Sanchez, Elise P; Yanes, Licy L; Gomez-Sanchez, Celso E

2006-08-01

Regulator of G protein signaling (RGS) proteins interact with Galpha-subunits of heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and finalizing the intracellular signaling triggered by the G protein-coupled receptor-ligand interaction. Angiotensin (Ang) II interacts with its G protein-coupled receptor in zona glomerulosa adrenal cells and triggers a cascade of intracellular signals that regulates steroidogenesis and proliferation. We studied Ang II-mediated regulation of RGS2, the role of RGS2 in steroidogenesis, and the intracellular signal events involved in H295R human adrenal cells. We report that both H295R cells and human adrenal gland express RGS2 mRNA. In H295R cells, Ang II caused a rapid and transient increase in RGS2 mRNA levels quantified by real-time RT-PCR. Ang II effects were mimicked by calcium ionophore A23187 and blocked by calcium channel blocker nifedipine. Ang II effects also were blocked by calmodulin antagonists (W-7 and calmidazolium) and calcium/calmodulin-dependent kinase antagonist KN-93. RGS2 overexpression by retroviral infection in H295R cells caused a decrease in Ang II-stimulated aldosterone secretion but did not modify cortisol secretion. In reporter assays, RGS2 decreased Ang II-mediated aldosterone synthase up-regulation. These results suggest that Ang II up-regulates RGS2 mRNA by the calcium/calmodulin-dependent kinase pathway in H295R cells. RGS2 overexpression specifically decreases aldosterone secretion through a decrease in Ang II-mediated aldosterone synthase-induced expression. In conclusion, RGS2 expression is induced by Ang II to terminate the intracellular signaling cascade generated by Ang II. RGS2 alterations in expression levels or functionality could be implicated in deregulations of Ang II signaling and abnormal aldosterone secretion by the adrenal gland.

UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells

PubMed Central

Gyenis, Ákos; Umlauf, David; Újfaludi, Zsuzsanna; Boros, Imre; Ye, Tao; Tora, Làszlò

2014-01-01

Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2–4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5–6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation. PMID:25058334

A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galvis-Pareja, David; Centro Estudios Moleculares de la Célula; Zapata-Torres, Gerald

2014-08-15

Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca{sup 2+} channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca{sup 2+} channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca{sup 2+} channel-blocking activity and antioxidant properties. The Ca{sup 2+} channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flowmore » cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca{sup 2+} channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca{sup 2+} channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca{sup 2+} entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca{sup 2+} blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca{sup 2+} blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties.« less

Rac1 Protein Signaling Is Required for DNA Damage Response Stimulated by Topoisomerase II Poisons*

PubMed Central

Huelsenbeck, Stefanie C.; Schorr, Anne; Roos, Wynand P.; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

2012-01-01

To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons. PMID:23012366

Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.

PubMed

Huelsenbeck, Stefanie C; Schorr, Anne; Roos, Wynand P; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

2012-11-09

To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons.

Transient left septal and anterior fascicular block associated with type 1 electrocardiographic Brugada pattern.

PubMed

Pérez-Riera, Andrés Ricardo; Barbosa-Barros, Raimundo; Penachini da Costa de Rezende Barbosa, Marianne; Daminello-Raimundo, Rodrigo; de Abreu, Luiz Carlos

The left septal fascicular block (LSFB) or blockage of the middle fibers of the left bundle branch is probably caused mainly by - in the developed world - the proximal obstruction of the left anterior descending artery (LAD) before its first anterior septal perforator branch (S 1 ). The association of transient LSFB and left anterior fascicular block (LAFB) - left bifascicular block - and the electrocardiographic type 1 Brugada pattern (BrP) has not been described in the literature yet. Copyright © 2017 Elsevier Inc. All rights reserved.

Isobolographic analysis of the interaction between cadmium (II) and sodium sulphate: toxicological consequences.

PubMed

Mera, Roi; Torres, Enrique; Abalde, Julio

2016-02-01

Sulphate is an essential nutrient for autotrophic organisms and has been shown to have important implications in certain processes of tolerance to cadmium toxicity. Sodium sulphate is the main salt of sulphate in the natural environments. The concentration of this salt is increasing in the aquatic environments due to environmental pollution. The aim of this study was to investigate, using an analysis of isobolograms, the type and the degree of the interaction between Cd(II) and sodium sulphate in the freshwater microalga Chlamydomonas moewusii. Two blocks of experiments were performed, one at sub-optimal sodium sulphate concentrations (<14.2 mg/L) and the other at supra-optimal concentrations (>14.2 mg/L). Three fixed ratios (2:1, 1:1, and 1:2) of the individual EC50 for cadmium and sodium sulphate were used within each block. The isobolographic analysis of interaction at sub-optimal concentrations showed a stronger antagonistic effect with values of interaction index (γ) between 1.46 and 3.4. However, the isobologram with sodium sulphate at supra-optimal concentrations revealed a slight but significant synergistic effect between both chemicals with an interaction index between 0.54 and 0.64. This synergic effect resulted in the potentiation of the toxic effects of cadmium, synergy that was related to the increase of the ionic strength and of two species of cadmium, CdSO4 (aq), and Cd(SO4)2(2-) , in the medium. Results of the current study suggest that sodium sulphate is able to perform a dual antagonist/synergist effect on cadmium toxicity. This role was concentration dependent.

LipidII: Just Another Brick in the Wall?

PubMed Central

Scheffers, Dirk-Jan; Tol, Menno B.

2015-01-01

Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s) of LipidII in bacterial cell biology has been slow. The focus of this review is on exciting new developments, both with respect to antibacterials targeting LipidII as well as the emerging role of LipidII in organizing the membrane and cell wall synthesis. It appears that on both sides of the membrane, LipidII plays crucial roles in organizing cytoskeletal proteins and peptidoglycan synthesis machineries. Finally, the recent discovery of no less than three different categories of LipidII flippases will be discussed. PMID:26679002

The Haw River Sites: Archaeological Investigations at Two Stratified Sites in the North Carolina Piedmont. Volume III.

DTIC Science & Technology

1982-04-01

Excavation Unit 5 - Square 8 - Level 4 - Feature 12 - n - 12 (ID numbers 368-379 in Appendix 3, Table 3) Vessel II Block C - Excavation Unit 6 - Square 8...Level 4 - Feature 7 - See Figure 7.13 - n 38 (ID numbers 380-417 In Appendix 3, Table 3) OO Vessel Ill Block C - Excavation Unit 7 - Square 1 - levels...4-8 - Feature 5 - See Figure 7.12 - n - 90 (ID numbers 418-507 In Appendix 3, Table 3) Vessel IV Block C - Excavation Unit 7 - Square 1 - Levels 4-8

Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt signaling pathway and an inflammatory response in adipose tissue.

PubMed

Sun, Ruixin; Wu, Yi; Hou, Weihua; Sun, Zujun; Wang, Yuxiong; Wei, Huanhuan; Mo, Wei; Yu, Min

2017-01-01

Insulin resistance is a major metabolic abnormality in a large majority of patients with type II diabetes. Bromodomain-containing protein 2 (Brd2), a transcriptional co-activator/co-repressor with switch mating type/sucrose non-fermenting (SWI/SNF)-like functions that regulates chromatin, suppresses adipocyte differentiation and regulates pancreatic β-cell biology. However, the effects of Brd2 on insulin resistance remain unknown. Here, overexpression of Brd2 in white adipose tissue of wild-type (WT) mice led to insulin resistance. Brd2 overexpression induced the expression of nuclear Factor-κΒ (NF-κΒ) target genes, mainly involving proinflammatory and chemotactic factors, in adipocytes. Furthermore, it decreased the expression of DEP domain containing mTOR-interacting protein (Deptor) to enhance mechanistic target of rapamycin (mTOR) signaling, thus blocking insulin signaling. Collectively, these results provided evidence for a novel role of Brd2 in chronic inflammation and insulin resistance, suggesting its potential in improving insulin resistance and treating metabolic disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

The Study of Blocking Agent on Lengkeng (Euphoria Logan Lour) Fruit Shell and Seed for Adsorption of Pb (II) from Aqueous Solution

NASA Astrophysics Data System (ADS)

Kurniawati, D.; Zein, R.; Chaidir, Z.; Aziz, H.

2018-04-01

The study focuses on the roles played by mayor functional groups(carboxyl) in the lengkeng shell for sorption of Pb (II). The biosorbent was characterized by FTIR and elemental analyses. The parameters such as pH, initial concentration, particle sizes, adsorbent dose and flow rate were also studied. The results showed that the optimum condition was at pH = 3, concentration 400 mg/l, 250 μm particle sizes, adsorbent dose 0,5 g and 2 ml/min flow rate with adsorption capacity 4,8933 mg/g(shell) and 5,2720 mg/g(seed). It is show that ion exchange play as a more important role in the sorption of Pb (II) on lengkeng shell and seed. Blocking of COOH groups by chemical esterification resulted in Pb important reduction in metal binding.The result showed that adsorption capacity of lengkeng shell uncreases until 63.67 % and lengkeng seed uncreases 98.70%.

Geological and Geochemical Characteristics of Skarn Type Lead-Zinc Deposit in Baoshan Block, Yunnan Province

NASA Astrophysics Data System (ADS)

Yao, Xue; Wang, Peng

2017-11-01

Baoshan block is an important Pb-Zn-Fe-Cu polymetallic ore-concentration area which is located in southern of the Sanjiang metallogenic belt in western Yunnan. The article is studying about the geological and geochemical characteristics of the skarn type lead-zinc deposit in Baoshan block. The skarn-type lead-zinc deposit Baoshan block is characterized by skarn and skarn marble, and the orebodies are layered, or bedded along the interlayer fault, which are significantly controlled by structure. The research about Stable isotope S, H and O indicates that the ore-forming fluids are mainly derived from magmatic water, partly mixed with parts of metamorphic water and atmospheric precipitation. The initial Sr isotopic Sr87/Sr86 ratio suggests that the ore-forming materials derived from deep concealed magmatic rock, age of Rb-Sr mineralization is similar to that of Yanshanian granite. In conclusion, the Yanshanian tectonic-magmatic-fluid coupling mineralization of Yanshan formation is the main reason for the skarn-type lead-zinc deposit in the Baoshan block.

Report on: Connecticut River Streambank Erosion Study, Massachusetts, New Hampshire and Vermont

DTIC Science & Technology

1979-11-01

Plastic filter cloths are used with considerable success beneath tiprap and other revetment materials such as articulated concrete blocks . The...rihutior unlimited II. SUPPLEMENTARY NOTES It. KEY WORDS (Continue on fever&e elde ifneceeeery and identify by block number). alluvial channel...erosion boat waves shear stress rock riprap lower bank erosion revetments flow control vegetation 20. ABSTRACT (Continue on reverse aide if neceesary and

Overlapping Yet Response-Specific Transcriptome Alterations Characterize the Nature of Tobacco-Pseudomonas syringae Interactions.

PubMed

Bozsó, Zoltán; Ott, Péter G; Kámán-Tóth, Evelin; Bognár, Gábor F; Pogány, Miklós; Szatmári, Ágnes

2016-01-01

In this study transcriptomic alterations of bacterially induced pattern triggered immunity (PTI) were compared with other types of tobacco-Pseudomonas interactions. In addition, using pharmacological agents we blocked some signal transduction pathways (Ca(2+) influx, kinases, phospholipases, proteasomic protein degradation) to find out how they contribute to gene expression during PTI. PTI is the first defense response of plant cells to microbes, elicited by their widely conserved molecular patterns. Tobacco is an important model of Solanaceae to study resistance responses, including defense mechanisms against bacteria. In spite of these facts the transcription regulation of tobacco genes during different types of plant bacterial interactions is not well-described. In this paper we compared the tobacco transcriptomic alterations in microarray experiments induced by (i) PTI inducer Pseudomonas syringae pv. syringae type III secretion mutant (hrcC) at earlier (6 h post inoculation) and later (48 hpi) stages of defense, (ii) wild type P. syringae (6 hpi) that causes effector triggered immunity (ETI) and cell death (HR), and (iii) disease-causing P. syringae pv. tabaci (6 hpi). Among the different treatments the highest overlap was between the PTI and ETI at 6 hpi, however, there were groups of genes with specifically altered activity for either type of defenses. Instead of quantitative effects of the virulent P. tabaci on PTI-related genes it influenced transcription qualitatively and blocked the expression changes of a special set of genes including ones involved in signal transduction and transcription regulation. P. tabaci specifically activated or repressed other groups of genes seemingly not related to either PTI or ETI. Kinase and phospholipase A inhibitors had highest impacts on the PTI response and effects of these signal inhibitors on transcription greatly overlapped. Remarkable interactions of phospholipase C-related pathways with the proteasomal system were also observable. Genes specifically affected by virulent P. tabaci belonged to various previously identified signaling routes, suggesting that compatible pathogens may modulate diverse signaling pathways of PTI to overcome plant defense.

Down-regulation of angiotensin II receptor subtypes and desensitization of cyclic GMP production in neuroblastoma N1E-115 cells.

PubMed

Reagan, L P; Ye, X; Maretzski, C H; Fluharty, S J

1993-01-01

Murine neuroblastoma N1E-115 cells possess membranous receptors for the octapeptide angiotensin II (AngII) whose density is substantially increased by in vitro differentiation. Incubation of differentiated N1E-115 cells with AngII produced a rapid decrease in receptor density, but did not alter the affinity of these receptors for either 125I-AngII or the high-affinity antagonist 125I-[Sarc1,Ile8]-AngII. This apparent down-regulation was dose related with an ED50 of 1 nM, and maximal decreases of approximately 90% were obtained with 100 nM AngII. Receptor loss from differentiated cell membranes was unaffected by incubations of membranes obtained from agonist-exposed cells with non-hydrolyzable analogues of GTP for 60 min at 37 degrees C to ensure dissociation of the ligand. Partial loss of AngII receptors was apparent within 5 min of agonist exposure, whereas maximal declines were not observed until 30 min. This temporal pattern resulted from a preferential decrease in the AT1 receptor subtype during the first 5 min, followed by a decline in both AT1 and AT2 receptors with longer periods of agonist exposure. The loss of membranous receptors was reversible with partial recovery observed after 4 h, and with nearly full recovery observed 18 h after exposure of the cells to AngII. However, the long-term recovery of receptor density was blocked by the protein synthesis inhibitor, cycloheximide. The heptapeptide angiotensin III produced a similar down-regulation of receptors, and the high-affinity antagonist [Sarc1,Thr8]-AngII blocked agonist-induced down-regulation. Finally, the apparent loss of cell surface AngII receptors decreased the ability of AngII to stimulate cyclic GMP production within intact N1E-115 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative evaluation of structured oil systems: Shellac oleogel, HPMC oleogel, and HIPE gel.

PubMed

Patel, Ashok R; Dewettinck, Koen

2015-11-01

In lipid-based food products, fat crystals are used as building blocks for creating a crystalline network that can trap liquid oil into a 3D gel-like structure which in turn is responsible for the desirable mouth feel and texture properties of the food products. However, the recent ban on the use of trans-fat in the US, coupled with the increasing concerns about the negative health effects of saturated fat consumption, has resulted in an increased interest in the area of identifying alternative ways of structuring edible oils using non-fat-based building blocks. In this paper, we give a brief account of three alternative approaches where oil structuring was carried out using wax crystals (shellac), polymer strands (hydrophilic cellulose derivative), and emulsion droplets as structurants. These building blocks resulted in three different types of oleogels that showed distinct rheological properties and temperature functionalities. The three approaches are compared in terms of the preparation process (ease of processing), properties of the formed systems (microstructure, rheological gel strength, temperature response, effect of water incorporation, and thixotropic recovery), functionality, and associated limitations of the structured systems. The comparative evaluation is made such that the new researchers starting their work in the area of oil structuring can use this discussion as a general guideline. Various aspects of oil binding for three different building blocks were studied in this work. The practical significance of this study includes (i) information on the preparation process and the concentrations of structuring agents required for efficient gelation and (ii) information on the behavior of oleogels to temperature, applied shear, and presence of water. This information can be very useful for selecting the type of structuring agents keeping the final applications in mind. For detailed information on the actual edible applications (bakery, chocolate, and spreads) which are based on the oleogel systems described in this manuscript, the readers are advised to refer our recent papers published elsewhere. (Food & Function 2014, 5, 645-652 and Food & Function 2014, 5, 2833-2841).

Interaction between FKBP5 gene and childhood trauma on psychosis, depression and anxiety symptoms in a non-clinical sample.

PubMed

de Castro-Catala, Marta; Peña, Elionora; Kwapil, Thomas R; Papiol, Sergi; Sheinbaum, Tamara; Cristóbal-Narváez, Paula; Ballespí, Sergi; Barrantes-Vidal, Neus; Rosa, Araceli

2017-11-01

Childhood trauma has been associated with a heightened risk for presenting clinical and non-clinical psychopathology in adulthood. Genes related with the stress response, such as the FK506 binding protein 51 (FKBP5), are plausible candidates moderating the effects of childhood trauma on the emergence of such symptoms later on. The present study aimed to explore the moderating role of FKBP5 genetic variability on the association of different types of childhood trauma with subclinical psychosis, depression and anxiety in a non-clinical sample. Schizotypy, psychotic-like experiences, depression and anxiety symptoms and childhood trauma were assessed in 808 young adults. Two FKBP5 haplotypic blocks were detected: block 1 (rs3800373 - rs9296158 - rs1360780) and block 2 (rs9470080 - rs4713916). Subjects were classified in two groups according to whether they carried or not the risk haplotype previously described in the literature (block 1: CAT and block 2: TA). Linear regression analyses were used to study (i) the main effects of childhood trauma and FKBP5 haplotype blocks and (ii) their interaction effects on the mentioned forms of psychopathology. All childhood trauma scales, except sexual abuse, were associated with schizotypy, psychotic-like experiences, depression and anxiety symptoms. None of the analysed symptoms was associated with the main effects of FKBP5 genetic variability. However an interaction effect between block 1 and physical abuse was observed on anxiety, with lower scores in CAT carriers. This effect was driven by SNP 1 and 2. Moreover, an interaction effect between block 2 and physical abuse was identified on the variables tapping depressive and anxiety symptoms. Specifically, non-TA carrier subjects who were exposed to physical abuse were found to be at higher risk for depressive and anxiety symptoms. These effects were driven by SNP 5. No interaction effect was observed for the other variables. Our data suggest that exposure to childhood physical abuse may increase the risk for sub-clinical depressive and anxiety symptoms depending on FKBP5 genetic variability. Further research is needed to better elucidate the role of FKBP5 on mental health in clinical and non-clinical cohorts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Angiotensin II activates collagen type I gene in the renal vasculature of transgenic mice during inhibition of nitric oxide synthesis: evidence for an endothelin-mediated mechanism.

PubMed

Boffa, J J; Tharaux, P L; Placier, S; Ardaillou, R; Dussaule, J C; Chatziantoniou, C

1999-11-02

Hypertension is frequently associated with renal vascular fibrosis. The purpose of this study was to investigate whether angiotensin II (Ang II) is involved in this fibrogenic process. Experiments were performed on transgenic mice harboring the luciferase gene under the control of the collagen I-alpha(2) chain promoter [procolalpha(2)(I)]. Hypertension was induced by chronic inhibition of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME). Procolalpha(2)(I) activity started to increase in the renal vasculature after 4 weeks of L-NAME treatment (P<0.01) and at 14 weeks reached 3- and 8-fold increases over control in afferent arterioles and glomeruli, respectively (P<0.001). Losartan, an AT(1) receptor antagonist, given simultaneously with L-NAME prevented the increase of procolalpha(2)(I) levels and attenuated the development of renal vascular fibrosis without normalizing systolic pressure increase. Because we found previously that endothelin mediated renal vascular fibrosis in the L-NAME model, the interaction between Ang II, endothelin, and procolalpha(2)(I) was investigated in ex vivo and short-term in vivo experiments. In both conditions, the Ang II-induced activation of procolalpha(2)(I) in renal cortex was blocked by an endothelin receptor antagonist. During chronic inhibition of NO, the collagen I gene becomes activated, leading to the development of renal vascular fibrosis. Ang II is a major player in this fibrogenic process, and its effect on collagen I gene is independent of systemic hemodynamics and is at least partly mediated by the profibrogenic action of endothelin.

Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy in cardiomyocytes.

PubMed

Jesus, Itamar Couto Guedes de; Scalzo, Sérgio; Alves, Fabiana; Marques, Kariny; Rocha-Resende, Cibele; Bader, Michael; Santos, Robson A Souza; Guatimosim, Silvia

2018-06-01

The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. New members of this system have been characterized and shown to have biologically relevant actions. Alamandine and its receptor MrgD are recently identified components of RAS. In the cardiovascular system, alamandine actions included vasodilation, antihypertensive, and antifibrosis effects. Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal was twofold: 1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this axis to prevent angiotensin II (ANG II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by d-Pro 7 -ANG-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine-induced NO production was preserved in Mas -/- myocytes and lost in MrgD -/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD -/- myocytes. We also assessed the consequences of prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs) treated with ANG II. Treatment of NRCMs with alamandine prevented ANG II-induced hypertrophy. Moreover, the antihypertrophic actions of alamandine were mediated via MrgD and NO, since they could be prevented by d-Pro 7 -ANG-(1-7) or inhibitors of NO synthase or AMPK. β-Alanine, a MrgD agonist, recapitulated alamandine's cardioprotective effects in cardiomyocytes. Our data show that alamandine via MrgD induces AMPK/NO signaling to counterregulate ANG II-induced hypertrophy. These findings highlight the therapeutic potential of the alamandine/MrgD axis in the heart.

Moisture and Thermal Conductivity of Lightweight Block Walls

NASA Astrophysics Data System (ADS)

Joosep, R.

2015-11-01

This article examines thermal properties of lightweight block walls and their changes over the course of time. Three different types of lightweight blocks and two types of heat insulation are used in construction. Aeroc aerated concrete blocks are in use, as well as compacted LECA (Lightweight Expanded Clay Aggregate) Fibo blocks made from burned clay and Silbet blocks produced from oil shale ash. Expanded Thermisol EPS60F polystyrene plates and glass wool Isover OL-P plates are used for thermal insulation. The actual and computational values of thermal conductivity and the water draining properties of walls over time are compared in this article. Water draining from glass wool walls is relatively fast. Water-draining can take over a year in polystyrene insulated walls. All four wall constructions can be used as external walls, but care must be taken regarding the moisture content of the blocks during construction (the construction should be handled with care to minimise the moisture in the blocks), especially in polystyrene board-insulated walls.

Emergence of Pathogenic Coronaviruses in Cats by Homologous Recombination between Feline and Canine Coronaviruses

PubMed Central

Terada, Yutaka; Matsui, Nobutaka; Noguchi, Keita; Kuwata, Ryusei; Shimoda, Hiroshi; Soma, Takehisa; Mochizuki, Masami; Maeda, Ken

2014-01-01

Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3′-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5′-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently. PMID:25180686

On High and Low Starting Frequencies of Type II Radio Bursts

NASA Astrophysics Data System (ADS)

Sharma, J.; Mittal, N.

2017-06-01

We have studied the characteristics of type II radio burst during the period May 1996 to March 2015, for the solar cycle 23 and 24, observed by WIND/WAVES radio instrument. A total of 642 events were recorded by the instrument during the study period. We have divided the events with two starting frequency range (high > 1 MHz; low ≤ 1MHz) as type II1 (i.e., 1-16 MHz) radio burst and type II2 (i.e., 20 KHz - 1020 KHz) radio burst which constitute the DH and km type II radio burst observed by WIND spacecraft, and determined their time and frequency characteristics. The mean drift rate of type II1 and type II2 radio bursts is 29.76 × 10-4 MHz/s and 0.17 × 10-4 MHz/s respectively, which shows that type II1 with high start frequency hase larger drift rate than the type II2 with low starting frequencies. We have also reported that the start frequency and the drift rate of type II1 are in good correlation, with a linear correlation coefficient of 0.58.

KENNEDY SPACE CENTER, FLA. - A solid rocket booster (SRB) for the Delta II Heavy rocket that will launch the Space Infrared Telescope Facility (SIRTF) arrives at Launch Complex 17-B, Cape Canaveral Air Force Station. The Delta II Heavy features nine 46-inch-diameter, stretched SRBs. Consisting of three cryogenically cooled science instruments and an 0.85-meter telescope, SIRTF is one of NASA's largest infrared telescopes to be launched. SIRTF will obtain images and spectra by detecting the infrared energy, or heat, radiated by objects in space. Most of this infrared radiation is blocked by the Earth's atmosphere and cannot be observed from the ground.

NASA Image and Video Library

2003-07-22

KENNEDY SPACE CENTER, FLA. - A solid rocket booster (SRB) for the Delta II Heavy rocket that will launch the Space Infrared Telescope Facility (SIRTF) arrives at Launch Complex 17-B, Cape Canaveral Air Force Station. The Delta II Heavy features nine 46-inch-diameter, stretched SRBs. Consisting of three cryogenically cooled science instruments and an 0.85-meter telescope, SIRTF is one of NASA's largest infrared telescopes to be launched. SIRTF will obtain images and spectra by detecting the infrared energy, or heat, radiated by objects in space. Most of this infrared radiation is blocked by the Earth's atmosphere and cannot be observed from the ground.

Zinc(II) and lead(II) metal-organic networks driven by a multifunctional pyridine-carboxylate building block: Hydrothermal synthesis, structural and topological features, and luminescence properties

NASA Astrophysics Data System (ADS)

Yang, Ling; Li, Yu; You, Ao; Jiang, Juan; Zou, Xun-Zhong; Chen, Jin-Wei; Gu, Jin-Zhong; Kirillov, Alexander M.

2016-09-01

4-(5-Carboxypyridin-2-yl)isophthalic acid (H3L) was applied as a flexible, multifunctional N,O-building block for the hydrothermal self-assembly synthesis of two novel coordination compounds, namely 2D [Zn(μ3-HL)(H2O)]n·nH2O (1) and 3D [Pb2(μ5-HL)(μ6-HL)]n (2) coordination polymers (CPs). These compounds were obtained in aqueous medium from a mixture containing zinc(II) or lead(II) nitrate, H3L, and sodium hydroxide. The products were isolated as stable crystalline solids and were characterized by IR spectroscopy, elemental, thermogravimetric (TGA), powder (PXRD) and single-crystal X-ray diffraction analyses. Compound 1 possesses a 2D metal-organic layer with the fes topology, which is further extended into a 3D supramolecular framework via hydrogen bonds. In contrast, compound 2 features a very complex network structure, which was topologically classified as a binodal 5,6-connected net with the unique topology defined by the point symbol of (47.63)(49.66). Compounds 1 and 2 disclose an intense blue or green luminescent emission at room temperature.

Positive Feedback between Transcriptional and Kinase Suppression in Nematodes with Extraordinary Longevity and Stress Resistance

PubMed Central

Bharill, Puneet; Shmookler Reis, Robert J.

2009-01-01

Insulin/IGF-1 signaling (IIS) regulates development and metabolism, and modulates aging, of Caenorhabditis elegans. In nematodes, as in mammals, IIS is understood to operate through a kinase-phosphorylation cascade that inactivates the DAF-16/FOXO transcription factor. Situated at the center of this pathway, phosphatidylinositol 3-kinase (PI3K) phosphorylates PIP2 to form PIP3, a phospholipid required for membrane tethering and activation of many signaling molecules. Nonsense mutants of age-1, the nematode gene encoding the class-I catalytic subunit of PI3K, produce only a truncated protein lacking the kinase domain, and yet confer 10-fold greater longevity on second-generation (F2) homozygotes, and comparable gains in stress resistance. Their F1 parents, like weaker age-1 mutants, are far less robust—implying that maternally contributed trace amounts of PI3K activity or of PIP3 block the extreme age-1 phenotypes. We find that F2-mutant adults have <10% of wild-type kinase activity in vitro and <60% of normal phosphoprotein levels in vivo. Inactivation of PI3K not only disrupts PIP3-dependent kinase signaling, but surprisingly also attenuates transcripts of numerous IIS components, even upstream of PI3K, and those of signaling molecules that cross-talk with IIS. The age-1(mg44) nonsense mutation results, in F2 adults, in changes to kinase profiles and to expression levels of multiple transcripts that distinguish this mutant from F1 age-1 homozygotes, a weaker age-1 mutant, or wild-type adults. Most but not all of those changes are reversed by a second mutation to daf-16, implicating both DAF-16/ FOXO–dependent and –independent mechanisms. RNAi, silencing genes that are downregulated in long-lived worms, improves oxidative-stress resistance of wild-type adults. It is therefore plausible that attenuation of those genes in age-1(mg44)-F2 adults contributes to their exceptional survival. IIS in nematodes (and presumably in other species) thus involves transcriptional as well as kinase regulation in a positive-feedback circuit, favoring either survival or reproduction. Hyperlongevity of strong age-1(mg44) mutants may result from their inability to reset this molecular switch to the reproductive mode. PMID:19360094

Angiotensin II AT2 receptor decreases AT1 receptor expression and function via nitric oxide/cGMP/Sp1 in renal proximal tubule cells from Wistar–Kyoto rats

PubMed Central

Yang, Jian; Chen, Caiyu; Ren, Hongmei; Han, Yu; He, Duofen; Zhou, Lin; Hopfer, Ulrich; Jose, Pedro A.; Zeng, Chunyu

2013-01-01

Background The renin–angiotensin (Ang) system controls blood pressure, in part, by regulating renal tubular sodium transport. In the kidney, activation of the angiotensin II type 1 (AT1) receptor increases renal sodium reabsorption, whereas the angiotensin II type 2 (AT2) receptor produces the opposite effect. We hypothesized that the AT2 receptor regulates AT1 receptor expression and function in the kidney. Methods and results In immortalized renal proximal tubule (RPT) cells from Wistar–Kyoto rats, CGP42112, an AT2 receptor agonist, decreased AT1 receptor mRNA and protein expression (P < 0.05), as assessed by reverse transcriptase-polymerase chain reaction and immunoblotting. The inhibitory effect of the AT2 receptor on AT1 receptor expression was blocked by the AT2 receptor antagonist, PD123319 (10−6 mol/l), the nitric oxide synthase inhibitor Nw-nitro-l-arginine methyl ester (10−4 mol/l), or the nitric oxide-dependent soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (10−5 mol/l), indicating that both nitric oxide and cyclic guanosine monophosphate (cGMP) were involved in the signaling pathway. Furthermore, CGP42112 decreased Sp1 serine phosphorylation and reduced the binding of Sp1 to AT1 receptor DNA. Stimulation with Ang II (10−11 mol/l per 30 min) enhanced Na+-K+-ATPase activity in RPT cells, which was prevented by pretreatment with CGP42112 (10−7 mol/l per 24 h) (P < 0.05). The above-mentioned results were confirmed in RPT cells from AT2 receptor knockout mice; AT1 receptor expression and Ang II-stimulated Na+-K+-ATPase activity were greater in these cells than in RPT cells from wild-type mice (P < 0.05). AT1/AT2 receptors co-localized and co-immunoprecipitated in RPT cells; short-term CGP42112 (10−7 mol/l per 30 min) treatment increased AT1/AT2 receptor co-immunoprecipitation (P < 0.05). Conclusions These results indicate that the renal AT2 receptor, via nitric oxide/cGMP/Sp1 pathway, regulates AT1 receptor expression and function, which may be important in the regulation of sodium excretion and blood pressure. PMID:22504846

Self-assembly of five 8-hydroxyquinolinate-based complexes: tunable core, supramolecular structure, and photoluminescence properties.

PubMed

Yuan, Guozan; Shan, Weilong; Qiao, Xuelong; Ma, Li; Huo, Yanping

2014-07-01

Five new Zn(II) complexes, namely [Zn(3)(L)(6)] (1), [Zn(2)(Cl)(2)(L)(2) (py)(2)] (2), [Zn(2)(Br)(2) (L)(2)(py)(2)] (3), [Zn(L)(2)(py)] (4), and [Zn(2)(OAc)(2)(L)(2)(py)(2)] (5), were prepared by the solvothermal reaction of ZnX(2) (X(-) =Cl(-), Br(-), F(-), and OAc(-)) salts with a 8-hydroxyquinolinate ligand (HL) that contained a trifluorophenyl group. All of the complexes were characterized by elemental analysis, IR spectroscopy, and powder and single-crystal X-ray crystallography. The building blocks exhibited unprecedented structural diversification and their self-assembly afforded one mononuclear, three binuclear, and one trinuclear Zn(II) structures in response to different anions and solvent systems. Complexes 1-5 featured four types of supramolecular network controlled by non-covalent interactions, such as π⋅⋅⋅π-stacking, C-H⋅⋅⋅π, hydrogen-bonding, and halogen-related interactions. Investigation of their photoluminescence properties exhibited disparate emission wavelengths, lifetimes, and quantum yields in the solid state. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tripeptidyl Peptidase II Regulates Sperm Function by Modulating Intracellular Ca2+ Stores via the Ryanodine Receptor

PubMed Central

Zhou, Yuchuan; Ru, Yanfei; Wang, Chunmei; Wang, Shoulin; Zhou, Zuomin; Zhang, Yonglian

2013-01-01

Recent studies have identified Ca2+ stores in sperm cells; however, it is not clear whether these Ca2+ stores are functional and how they are mobilized. Here, in vitro and in vivo, we determined that tripeptidyl peptidase II antagonists strongly activated the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. We demonstrated that in the absence of Ca2+, TPIII antagonists elevated the intracellular Ca2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca2+ could be blocked by the inhibitors of ryanodine receptors (RyRs) which are the main intracellular Ca2+ channels responsible for releasing stored Ca2+. Consistent with these results, indirect immunofluorescence assay using anti-RyR antibodies further validated the presence of RyR3 in the acrosomal region of mature sperm. Thus, TPPII can regulate sperm maturation by modulating intracellular Ca2+ stores via the type 3 RyR. PMID:23818952

Water exit pathways and proton pumping mechanism in B-type cytochrome c oxidase from molecular dynamics simulations.

PubMed

Yang, Longhua; Skjevik, Åge A; Han Du, Wen-Ge; Noodleman, Louis; Walker, Ross C; Götz, Andreas W

2016-09-01

Cytochrome c oxidase (CcO) is a vital enzyme that catalyzes the reduction of molecular oxygen to water and pumps protons across mitochondrial and bacterial membranes. While proton uptake channels as well as water exit channels have been identified for A-type CcOs, the means by which water and protons exit B-type CcOs remain unclear. In this work, we investigate potential mechanisms for proton transport above the dinuclear center (DNC) in ba3-type CcO of Thermus thermophilus. Using long-time scale, all-atom molecular dynamics (MD) simulations for several relevant protonation states, we identify a potential mechanism for proton transport that involves propionate A of the active site heme a3 and residues Asp372, His376 and Glu126(II), with residue His376 acting as the proton-loading site. The proposed proton transport process involves a rotation of residue His376 and is in line with experimental findings. We also demonstrate how the strength of the salt bridge between residues Arg225 and Asp287 depends on the protonation state and that this salt bridge is unlikely to act as a simple electrostatic gate that prevents proton backflow. We identify two water exit pathways that connect the water pool above the DNC to the outer P-side of the membrane, which can potentially also act as proton exit transport pathways. Importantly, these water exit pathways can be blocked by narrowing the entrance channel between residues Gln151(II) and Arg449/Arg450 or by obstructing the entrance through a conformational change of residue Tyr136, respectively, both of which seem to be affected by protonation of residue His376. Copyright © 2016 Elsevier B.V. All rights reserved.

31 CFR 585.203 - Holding of certain types of blocked property in interest-bearing accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Holding of certain types of blocked property in interest-bearing accounts. 585.203 Section 585.203 Money and Finance: Treasury Regulations... OF BOSNIA AND HERZEGOVINA SANCTIONS REGULATIONS Prohibitions § 585.203 Holding of certain types of...

Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?

PubMed

Wang, Pei; Fedoruk, Matthew N; Rupert, Jim L

2008-01-01

In the decade since the angiotensin-converting enzyme (ACE) gene was first proposed to be a 'human gene for physical performance', there have been numerous studies examining the effects of ACE genotype on physical performance phenotypes such as aerobic capacity, muscle function, trainability, and athletic status. While the results are variable and sometimes inconsistent, and corroborating phenotypic data limited, carriers of the ACE 'insertion' allele (the presence of an alu repeat element in intron 16 of the gene) have been reported to have higher maximum oxygen uptake (VO2max), greater response to training, and increased muscle efficiency when compared with individuals carrying the 'deletion' allele (absence of the alu repeat). Furthermore, the insertion allele has been reported to be over-represented in elite athletes from a variety of populations representing a number of endurance sports. The mechanism by which the ACE insertion genotype could potentiate physical performance is unknown. The presence of the ACE insertion allele has been associated with lower ACE activity (ACEplasma) in number of studies, suggesting that individuals with an innate tendency to have lower ACE levels respond better to training and are at an advantage in endurance sporting events. This could be due to lower levels of angiotensin II (the vasoconstrictor converted to active form by ACE), higher levels of bradykinin (a vasodilator degraded by ACE) or some combination of the two phenotypes. Observations that individuals carrying the ACE insertion allele (and presumably lower ACEplasma) have an enhanced response to training or are over-represented amongst elite athletes raises the intriguing question: would individuals with artificially lowered ACEplasma have similar training or performance potential? As there are a number of drugs (i.e. ACE inhibitors and angiotensin II type 1 receptor antagonists [angiotensin receptor blockers--ARBs]) that have the ability to either reduce ACEplasma activity or block the action of angiotensin II, the question is relevant to the study of ergogenic agents and to the efforts to rid sports of 'doping'. This article discusses the possibility that ACE inhibitors and ARBs, by virtue of their effects on ACE or angiotensin II function, respectively, have performance-enhancing capabilities; it also reviews the data on the effects of these medications on VO2max, muscle composition and endurance capacity in patient and non-patient populations. We conclude that, while the direct evidence supporting the hypothesis that ACE-related medications are potential doping agents is not compelling, there are insufficient data on young, athletic populations to exclude the possibility, and there is ample, albeit indirect, support from genetic studies to suggest that they should be. Unfortunately, given the history of drug experimentation in athletes and the rapid appropriation of therapeutic agents into the doping arsenal, this indirect evidence, coupled with the availability of ACE-inhibiting and ACE-receptor blocking medications may be sufficiently tempting to unscrupulous competitors looking for a shortcut to the finish line.

Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

PubMed

Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

2016-01-01

During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

The Impact of Individual Differences, Types of Model and Social Settings on Block Building Performance among Chinese Preschoolers.

PubMed

Tian, Mi; Deng, Zhu; Meng, Zhaokun; Li, Rui; Zhang, Zhiyi; Qi, Wenhui; Wang, Rui; Yin, Tingting; Ji, Menghui

2018-01-01

Children's block building performances are used as indicators of other abilities in multiple domains. In the current study, we examined individual differences, types of model and social settings as influences on children's block building performance. Chinese preschoolers ( N = 180) participated in a block building activity in a natural setting, and performance was assessed with multiple measures in order to identify a range of specific skills. Using scores generated across these measures, three dependent variables were analyzed: block building skills, structural balance and structural features. An overall MANOVA showed that there were significant main effects of gender and grade level across most measures. Types of model showed no significant effect in children's block building. There was a significant main effect of social settings on structural features, with the best performance in the 5-member group, followed by individual and then the 10-member block building. These findings suggest that boys performed better than girls in block building activity. Block building performance increased significantly from 1st to 2nd year of preschool, but not from second to third. The preschoolers created more representational constructions when presented with a model made of wooden rather than with a picture. There was partial evidence that children performed better when working with peers in a small group than when working alone or working in a large group. It is suggested that future study should examine other modalities rather than the visual one, diversify the samples and adopt a longitudinal investigation.

Modeling study of mecamylamine block of muscle type acetylcholine receptors.

PubMed

Ostroumov, Konstantin; Shaikhutdinova, Asya; Skorinkin, Andrey

2008-04-01

The blocking action of mecamylamine on different types of nicotinic acetylcholine receptors (nAChRs) has been extensively studied and used as a tool to characterize the nAChRs from different synapses. However, mechanism of mecamylamine action was not fully explored for all types of nAChRs. In the present study, we provide brief description of the mecamylamine action on muscle nAChRs expressed at the frog neuromuscular junction. In this preparation mecamylamine block of nAChRs was accompanied by a use-dependent block relief induced by membrane depolarization combined with the activation of nAChRs by endogenous agonist acetylcholine (ACh). Further, three kinetic models of possible mecamylamine interaction with nAChRs were analyzed including simple open channel block, symmetrical trapping block and asymmetrical trapping block. This analysis suggested that mecamylamine action could be described on the basis of trapping mechanism, when the antagonist remained inside the channel even in the absence of bound agonist. Such receptors with trapped mecamylamine inside were predicted to have a closing rate constant about three times faster than resting one and a fast voltage-dependent unblocking rate constant. Specific experimental conditions and morphological organization of the neuromuscular synapses were considered to simulate time course of the mecamylamine block development. Thus, likewise for the neuronal nAChRs, the trapping mechanism determined the action of mecamylamine on synaptic neuromuscular currents evoked by the endogenous agonist acetylcholine (ACh), however specific morphological organization of the synaptic transmission delayed time development of the currents block.

A polyvalent hybrid protein elicits antibodies against the diverse allelic types of block 2 in Plasmodium falciparum merozoite surface protein 1.

PubMed

Tetteh, Kevin K A; Conway, David J

2011-10-13

Merozoite surface protein 1 (MSP1) of Plasmodium falciparum has been implicated as an important target of acquired immunity, and candidate components for a vaccine include polymorphic epitopes in the N-terminal polymorphic block 2 region. We designed a polyvalent hybrid recombinant protein incorporating sequences of the three major allelic types of block 2 together with a composite repeat sequence of one of the types and N-terminal flanking T cell epitopes, and compared this with a series of recombinant proteins containing modular sub-components and similarly expressed in Escherichia coli. Immunogenicity of the full polyvalent hybrid protein was tested in both mice and rabbits, and comparative immunogenicity studies of the sub-component modules were performed in mice. The full hybrid protein induced high titre antibodies against each of the major block 2 allelic types expressed as separate recombinant proteins and against a wide range of allelic types naturally expressed by a panel of diverse P. falciparum isolates, while the sub-component modules had partial antigenic coverage as expected. This encourages further development and evaluation of the full MSP1 block 2 polyvalent hybrid protein as a candidate blood-stage component of a malaria vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

NMR structures of anti-HIV D-peptides derived from the N-terminus of viral chemokine vMIP-II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Mayuko; Liu Dongxiang; Kumar, Santosh

2005-09-30

The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi's sarcoma-associated herpesvirus has unique biological activities in that it blocks the cell entry by several different human immunodeficiency virus type 1 (HIV-1) strains via chemokine receptors including CXCR4 and CCR5. In this paper, we report the solution structure of all-D-amino acid peptides derived from the N-terminus of vMIP-II, which have been shown to have strong CXCR4 binding activity and potently inhibit HIV-1 entry via CXCR4, by using long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments. Both of all-D-peptides vMIP-II (1-10) and vMIP-II (1-21), which are designated as DV3 and DV1,more » respectively, have higher CXCR4 binding ability than their L-peptide counterparts. They are partially structured in aqueous solution, displaying a turn-like structure over residues 5-8. The small temperature coefficients of His-6 amide proton for both peptides also suggest the formation of a small hydrophobic pocket centered on His-6. The structural features of DV3 are very similar to the reported solution structure of all-L-peptide vMIP-II (1-10) [M.P. Crump, E. Elisseeva, J. Gong, I. Clark-Lewis, B.D. Sykes, Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10), FEBS Lett. 489 (2001) 171], which is consistent with the notion that D- and L-enantiomeric peptides can adopt mirror image conformations. The NMR structures of the D-peptides provide a structural basis to understand their mechanism of action and design new peptidomimetic analogs to further explore the structure-activity relationship of D-peptide ligand binding to CXCR4.« less

Seawalls, Bulkheads and Quaywalls. Design Manual 25.4.

DTIC Science & Technology

1981-07-01

slopes, such as concrete block revetment , also can result in a large quantity of water overtopping the wall. Where overtopping is a serious problem...small precast units such as the concrete block revetment shown in Figure 1, type D and the precast stepped walls shown in Figure 1, types E and G, should...16. DISTRIBUTION STATEMENT (of this Report) Unclassified/Unlimited ..... 17. DISTRIBUTION STATEMENT (of the abstract entered In Block 20, if different

Lunar highland rocks - Element partitioning among minerals. II - Electron microprobe analyses of Al, P, Ca, Ti, Cr, Mn and Fe in olivine

NASA Technical Reports Server (NTRS)

Smith, J. V.; Hansen, E. C.; Steele, I. M.

1980-01-01

Lunar olivines from anorthosites, granulitic impactites, and rocks in the Mg-rich plutonic trend were subjected to electron probe measurements for Al, P, Ca, Ti, Cr and Mn, which show that the FeO/MnO ratio for lunar olivines lies between 80 and 110 with little difference among the rock types. The low values of Ca in lunar olivines indicate slow cooling to subsolidus temperatures, with blocking temperatures of about 750 C for 67667 and 1000 C for 60255,73-alpha determined by the Finnerty and Boyd (1978) experiments. An important paradox is noted in the low Ti content of Fe-rich olivines from anorthosites, although both Ti and Fe tend to become enriched in liquid during fractional distillation. Except for Ca and Mn, olivine from anorthosites has lower minor element values than other rock types. Formation from a chemically distinct system is therefore implied.

Subneurotoxic copper(II)-induced NF-κB-dependent microglial activation is associated with mitochondrial ROS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Zhuqin; Yu, Fengxiang; Gong, Ping

2014-04-15

Microglia-mediated neuroinflammation and the associated neuronal damage play critical roles in the pathogenesis of neurodegenerative disorders. Evidence shows an elevated concentration of extracellular copper(II) in the brains of these disorders, which may contribute to neuronal death through direct neurotoxicity. Here we explored whether extracellular copper(II) triggers microglial activation. Primary rat microglia and murine microglial cell line BV-2 cells were cultured and treated with copper(II). The content of tumor necrosis factor-α (TNF-α) and nitric oxide in the medium was determined. Extracellular hydrogen peroxide was quantified by a fluorometric assay with Amplex Red. Mitochondrial superoxide was measured by MitoSOX oxidation. At subneurotoxicmore » concentrations, copper(II) treatment induced a dose- and time-dependent release of TNF-α and nitric oxide from microglial cells, and caused an indirect, microglia-mediated neurotoxicity that was blocked by inhibition of TNF-α and nitric oxide production. Copper(II)-initiated microglial activation was accompanied with reduced IkB-α expression as well as phosphorylation and translocation of nuclear factor-κB (NF-κB) p65 and was blocked by NF-κB inhibitors (BAY11-7082 and SC-514). Moreover, copper(II) treatment evoked a rapid release of hydrogen peroxide from microglial cells, an effect that was not affected by NADPH oxidase inhibitors. N-acetyl-cysteine, a scavenger of reactive oxygen species (ROS), abrogated copper(II)-elicited microglial release of TNF-α and nitric oxide and subsequent neurotoxicity. Importantly, mitochondrial production of superoxide, paralleled to extracellular release of hydrogen peroxide, was induced after copper(II) stimulation. Our findings suggest that extracellular copper(II) at subneurotoxic concentrations could trigger NF-κB-dependent microglial activation and subsequent neurotoxicity. NADPH oxidase-independent, mitochondria-derived ROS may be involved in this activation. - Highlights: • Subneurotoxic copper(II) triggers NF-κB-dependent microglial activation. • This activation leads to hippocampal neuronal death. • This activation may involve mitochondria-derived reactive oxygen species.« less

Modic changes in lumbar spine: prevalence and distribution patterns of end plate oedema and end plate sclerosis.

PubMed

Xu, Lei; Chu, Bin; Feng, Yang; Xu, Feng; Zou, Yue-Fen

2016-01-01

The purpose of this study is to evaluate the distribution of end plate oedema in different types of Modic change especially in mixed type and to analyze the presence of end plate sclerosis in various types of Modic change. 276 patients with low back pain were scanned with 1.5-T MRI. Three radiologists assessed the MR images by T1 weighted, T2 weighted and fat-saturation T2 weighted sequences and classified them according to the Modic changes. Pure oedematous end plate signal changes were classified as Modic Type I; pure fatty end plate changes were classified as Modic Type II; and pure sclerotic end plate changes as Modic Type III. A mixed feature of both Types I and II with predominant oedematous signal change is classified as Modic I-II, and a mixture of Types I and II with predominant fatty change is classified as Modic II-I. Thus, the mixed types can further be subdivided into seven subtypes: Types I-II, Types II-I, Types I-III, Types III-I, Types II-III, Types III-II and Types I-III. During the same period, 52 of 276 patients who underwent CT and MRI were retrospectively reviewed to determine end plate sclerosis. (1) End plate oedema: of the 2760 end plates (276 patients) examined, 302 end plates showed Modic changes, of which 82 end plates showed mixed Modic changes. The mixed Modic changes contain 92.7% of oedematous changes. The mixed types especially Types I-II and Types II-I made up the majority of end plate oedematous changes. (2) End plate sclerosis: 52 of 276 patients were examined by both MRI and CT. Of the 520 end plates, 93 end plates showed Modic changes, of which 34 end plates have shown sclerotic changes in CT images. 11.8% of 34 end plates have shown Modic Type I, 20.6% of 34 end plates have shown Modic Type II, 2.9% of 34 end plates have shown Modic Type III and 64.7% of 34 end plates have shown mixed Modic type. End plate oedema makes up the majority of mixed types especially Types I-II and Types II-I. The end plate sclerosis on CT images may not just mean Modic Type III but does exist in all types of Modic changes, especially in mixed Modic types, and may reflect vertebral body mineralization rather than change in the bone marrow. End plate oedema and end plate sclerosis are present in a large proportion of mixed types.

Superconducting magnet and fabrication method

NASA Technical Reports Server (NTRS)

Israelsson, Ulf E. (Inventor); Strayer, Donald M. (Inventor)

1994-01-01

A method of trapping a field in a block of superconductor material, includes providing (i) a block of material defining a bore, (ii) a high permeability core within the bore that defines a low reluctance path through the bore, (iii) a high permeability external structure on the exterior of the block of material that defines a low reluctance path between opposite ends of the core, and (iv) an electromagnet configured to apply a magnetic field around the high permeability core. The method proceeds by energizing the electromagnet to produce an applied magnetic field around the high permeability core, cooling the block of material sufficiently to render the block of material superconducting, de-energizing the electromagnet to result in a trapped magnetic field, and at least partially removing the low reluctance path defined by the core and the external structure in order to increase the magnetic flux density of the trapped magnetic field.

An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

PubMed Central

Minetti, Giulia C.; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N.; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji

2014-01-01

The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings. PMID:24298022

Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis.

PubMed

Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi; Ohshima, Yasuhiro; Tago, Fumitoshi; Masada, Ayako; Kojima, Shuji

2008-07-01

We previously reported attenuation of autoimmune disease by low-dose gamma-ray irradiation in MRL-lpr/lpr mice. Here, we studied the effect of low-dose gamma-ray irradiation on collagen-induced arthritis (CIA) in DBA/1J mice. Mice were immunized with type II collagen, and exposed to low-dose gamma-rays (0.5 Gy per week for 5 weeks). Paw swelling, redness, and bone degradation were suppressed by irradiation, which also delayed the onset of pathological change and reduced the severity of the arthritis. Production of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6, which play important roles in the onset of CIA, was suppressed by the irradiation. The level of anti-type II collagen antibody, which is essential for the onset of CIA, was also lower in irradiated CIA mice. The population of plasma cells was increased in CIA mice, but irradiation blocked this increase. Since regulatory T cells are known to be involved in suppression of autoimmune disease, the population of CD4(+)CD25(+)Foxp3(+) regulatory T cells was measured. Intriguingly, a significant increase of these regulatory T cells was found in irradiated CIA mice. Overall, our data suggest that low-dose gamma-ray irradiation could attenuate CIA through suppression of pro-inflammatory cytokines and autoantibody production, and induction of regulatory T cells.

Molecular cloning, expression and characterization of albolamin: a type P-IIa snake venom metalloproteinase from green pit viper (Cryptelytrops albolabris).

PubMed

Jangprasert, Panchalee; Rojnuckarin, Ponlapat

2014-03-01

Snake venom metalloproteinases (SVMPs) can damage vessel wall, degrade clotting factors, inhibit integrins and block platelet functions. Studying them not only gives us deeper insights in pathogenesis of snakebites, but also potentially yields novel therapeutic agents. Here, we discovered a clone of an RGD-containing SVMP from the green pit viper (Cryptelytrops albolabris) venom gland cDNA library. Sequence analysis revealed that it belonged to the P-IIa subclass of SVMP comprising signal peptide, prodomain, metalloproteinase and disintegrin. Compared with other P-II SVMPs, it contained 2 additional conserved cysteines that were predicted to prevent the release of disintegrin from the metalloproteinase domain in the mature protein. The N-terminal histidine-tagged construct of metalloproteinase and disintegrin domains of albolamin was inserted into the pPICZαA vector and expressed in Pichia pastoris. The recombinant protein molecular weight was approximately 35 kDa on Western blot probed with anti-polyhistidine antibody. The recombinant albolamin could digest human type IV collagen starting within 15 min after incubation. In addition, it dose-dependently inhibited collagen-induced platelet aggregation with the IC50 of 1.8 μM. However, there was no effect on ADP-induced platelet aggregation. Therefore, the inhibition mechanism is probably through blocking collagen receptor(s). Albolamin activities probably contributed to pathology of green pit viper bites. Its disintegrin domain deserves further studies for the potential to be a useful agent affecting platelet functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells*

PubMed Central

Lam, Vincent M.; Salahpour, Ali

2016-01-01

A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function. PMID:27555326

Novel mechanism of cardiac protection by valsartan: synergetic roles of TGF-β1 and HIF-1α in Ang II-mediated fibrosis after myocardial infarction.

PubMed

Sui, Xizhong; Wei, Hongchao; Wang, Dacheng

2015-08-01

Transforming growth factor (TGF)-β1 is a known factor in angiotensin II (Ang II)-mediated cardiac fibrosis after myocardial infarction (MI). Hypoxia inducible factor-1 (Hif-1α) was recently demonstrated to involve in the tissue fibrosis and influenced by Ang II. However, whether Hif-1α contributed to the Ang II-mediated cardiac fibrosis after MI, and whether interaction or synergetic roles between Hif-1α and TGF-β pathways existed in the process was unclear. In vitro, cardiac cells were incubated under hypoxia or Ang II to mimic ischaemia. In vivo, valsartan was intravenously injected into Sprague-Dawley rats with MI daily for 1 week; saline and hydralazine (another anti-hypertensive agent like valsartan) was used as control. The fibrosis-related proteins were detected by Western blotting. Cardiac structure and function were assessed with multimodality methods. We demonstrated in vitro that hypoxia would induce the up-regulation of Ang II, TGF-β/Smad and Hif-1α, which further induced collagen accumulation. By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up-regulation of TGF-β/Smad and Hif-1α was through the Ang II-mediated pathway. By administering TGF-β or dimethyloxalylglycine, we determined that both TGF-β/Smad and Hif-1α contributed to Ang II-mediated collagen accumulation and a synergetic effect between them was observed. Consistent with in vitro results, valsartan significantly attenuated the expression of TGF-β/Smad, Hif-1α and fibrosis-related protein in rats after MI. Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine. Our study may provide novel insights into the mechanisms of Ang II-induced cardiac fibrosis as well as into the cardiac protection of valsartan. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Critical Role of Hepatic Cyp450s in the Testis-Specific Toxicity of (5R)-5-Hydroxytriptolide in C57BL/6 Mice

PubMed Central

Yu, Cunzhi; Li, Yu; Liu, Mingxia; Gao, Man; Li, Chenggang; Yan, Hong; Li, Chunzhu; Sun, Lihan; Mo, Liying; Wu, Chunyong; Qi, Xinming; Ren, Jin

2017-01-01

Low solubility, tissue accumulation, and toxicity are chief obstacles to developing triptolide derivatives, so a better understanding of the pharmacokinetics and toxicity of triptolide derivatives will help with these limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative immunosuppressant in a conditional knockout (KO) mouse model with liver-specific deletion of CYP450 reductase. Compared to wild type (WT) mice, after LLDT-8 treatment, KO mice suffered severe testicular toxicity (decreased testicular weight, spermatocytes apoptosis) unlike WT mice. Moreover, KO mice had greater LLDT-8 exposure as confirmed with elevated AUC and Cmax, increased drug half-life, and greater tissue distribution. γ-H2AX, a marker of meiosis process, its localization and protein level in testis showed a distinct meiosis block induced by LLDT-8. RNA polymerase II (Pol II), an essential factor for RNA storage and synapsis in spermatogenesis, decreased in testes of KO mice after LLDT-8 treatment. Germ-cell line based assays confirmed that LLDT-8 selectively inhibited Pol II in spermatocyte-like cells. Importantly, the analysis of androgen receptor (AR) related genes showed that LLDT-8 did not change AR-related signaling in testes. Thus, hepatic CYP450s were responsible for in vivo metabolism and clearance of LLDT-8 and aggravated testicular injury may be due to increased LLDT-8 exposure in testis and subsequent Pol II reduction. PMID:29209210

Inhibitory effect of auranofin (I) and chloroquine (II) on bone degradation induced by the interleukin 1-like (IL-1-like) factor released from rheumatoid synovial tissue (RAST) in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodges, Y.; Maser, M.R.; Britton, M.C.

1986-03-01

RAST, maintained in organ culture, releases two distinct types of bone resorptive factors and one co-resorptive factor. The first is prostaglandin E/sub 2/ (PGE/sub 2/), while the second is a protein with properties of IL-1. The co-resorptive factor collagenase, cannot induce bone resorption by itself, but augments the bone resorptive activity initiated by either PGE/sub 2/ or the IL-l-like factor. Bone resorptive activity was assessed by measuring the release of /sup 45/Ca from prelabelled rat fetal bones. We investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) and two disease-modifying anti-rheumatic drugs (DMARDs), (I) and (II), on bone degradation mediatedmore » by the IL-l-like factor. None of the NSAIDs tested inhibited bone degradation at 5 x 10/sup -5/ M. On the other hand, both (I) and (II) inhibited bone degradation 60 to 100% at 1 x 10/sup -6/ M and 8 x 10/sup -6/ M respectively. They can inhibit the action of IL-l-like factor on bone at therapeutically attainable concentrations. Additionally, both (I) and (II) block the release of collagenase from the organ culture of RAST with IC/sub 50/s of 5 x 10/sup -6/ M. This unique ability to inhibit collagenase release may contribute to their effectiveness is preventing bone loss in this test model.« less

Commencement Bay Study. Volume II. Land and Water Use.

DTIC Science & Technology

1981-12-31

DISTRISUTION STATEMENT (of We Report) Approved for public release, distribution unlimited 17. DISTRIBUTION STATEMENT (e1 the obearle nteed he Block ...the study area boundaries. With the exception of commercially zoned (C-1) lands extending for one-half block on the west side of Pearl Street from...ASARCO to cool slag and as noncontact cooling water in plant processes. While ASARCO uses more marine water than potable water, most other local

Geodynamic settings of microcontinents, non-volcanic islands and submerged continental marginal plateau formation

NASA Astrophysics Data System (ADS)

Dubinin, Evgeny; Grokholsky, Andrey; Makushkina, Anna

2016-04-01

Complex process of continental lithosphere breakup is often accompanied by full or semi isolation of small continental blocks from the parent continent such as microcontinents or submerged marginal plateaus. We present different types of continental blocks formed in various geodynamic settings. The process depends on thermo-mechanical properties of rifting. 1) The continental blocks fully isolated from the parent continent. This kind of blocks exist in submerged form (Elan Bank, the Jan-Mayen Ridge, Zenith Plateau, Gulden Draak Knoll, Batavia Knoll) and in non-submerged form in case of large block size. Most of listed submerged blocks are formed in proximity of hot-spot or plume. 2) The continental blocks semi-isolated from the parent continent. Exmouth Plateau, Vøring, Agulhas, Naturaliste are submerged continental plateaus of the indicated category; Sri Lanka, Tasmania, Socotra are islands adjacent to continent here. Nowadays illustration of this setting is the Sinai block located between the two continental rifts. 3) The submerged linear continental blocks formed by the continental rifting along margin (the Lomonosov Ridge). Suggested evolution of this paragraph is the rift propagation along existing transtensional (or another type) transform fault. Future example of this type might be the California Peninsula block, detached from the North American plate by the rifting within San-Andreas fault. 4) The submerged continental blocks formed by extensional processes as the result of asthenosphere flow and shear deformations. Examples are submerged blocks in the central and southern Scotia Sea (Terror Bank, Protector Basin, Discovery Bank, Bruce Bank etc.). 5) The continental blocks formed in the transform fault systems originated in setting of contradict rifts propagation in presence of structure barriers, rifts are shifted by several hundreds kilometers from each other. Examples of this geodynamic setting are Equatorial Atlantic at the initial development stage, and the transitional zone between Mohns and Gakkel Ridges. The research funded by RFBR, project № 15-05-03486.

Genetics Home Reference: distal hereditary motor neuropathy, type II

MedlinePlus

... hereditary motor neuropathy, type II Distal hereditary motor neuropathy, type II Printable PDF Open All Close All ... the expand/collapse boxes. Description Distal hereditary motor neuropathy, type II is a progressive disorder that affects ...

Serum agonistic autoantibodies against type-1 angiotensin II receptor titer in patients with epithelial ovarian cancer: a potential role in tumor cell migration and angiogenesis

PubMed Central

2013-01-01

Background Although agonistic autoantibodies against type-1 angiotensin-II receptor (AT1-AA) are frequently detected in women with preeclampsia, the clinical significance of AT1-AA in association with epithelial ovarian cancer (EOC) has not been identified. Methods In an attempt to clarify this issue, we measured serum AT1-AA titer from EOC patients (n = 89) and healthy normal subjects (n = 55), correlated AT1-AA titer with EOC stage and grade, and demonstrated the effects of purified AT1-AA on migration of ovarian cancer cells and angiogenesis of chick embryo chorioallantoic membrane. Results We found that the AT1-AA titer was significantly higher in EOC patients compared with healthy control subjects (1.77 ± 0.28 vs. 0.35 ± 0.05, P < 0.01). The positive rate was averaged by 72.1±2.5% in EOC patients and 15.5 ±1.5% in control (P < 0.01). Increased AT1-AA titer in EOC patients was associated with advanced stages and grades of EOC, and positively correlated with level of vascular endothelial growth factor (r = 0.855, P < 0.01). Furthermore, AT1-AA directly stimulated migration of ovarian cancer cells and enhanced microvascular density of chick embryo chorioallantoic membrane. These AT1-AA-mediated effects were significantly blocked either by an autoantibody-neutralizing peptide or an angiotensin II type I receptor antagonist, losartan. Conclusion Taken together, we found that a higher serum AT1-AA titer may be associated with advanced progression of EOC in patients and play an important role in development of EOC by promoting cancer cell migration and angiogenesis. These findings implicate that AT1-AA might be selected as a detectable biomarker and potential therapeutic target in diagnosis and treatment of EOC patients. PMID:23561060