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Kinds of Lies Terms modified by Lies Selected AbstractsPIOUS LIES: THE JUSTIFICATION OF STATES AND WELFARE STATESECONOMIC AFFAIRS, Issue 2 2004Anthony de Jasay Institutions, customs, laws are often, and sometimes implausibly, credited with efficiency. They serve a good purpose and if they had not arisen, we would have invented them. The claim is reassuring, though it may be no more than a pious lie. The creation of the state by social contract, and the adoption of supposedly rational customs by primitive peoples, serve as examples. Interpreting the welfare state as a mutual insurance scheme from which all can expect to profit is a classic of the kind. [source] ASSESSING WHAT LIES BENEATH THE SPATIAL DISTRIBUTION OF A ZOOARCHAEOLOGICAL RECORD: THE USE OF GIS AND SPATIAL CORRELATIONS AT EL MIRÓN CAVE (SPAIN)*ARCHAEOMETRY, Issue 3 2009A. B. MARÍN ARROYO Geographical Information Systems (GIS) are being incorporated into archaeology as a technique to improve the understanding of spatial organization and the relationships among finds within specific areas. Although their use as a basic tool in predicting the location of archaeological sites or in assessing the extent of their catchment areas is relatively common, in general, they have less often been applied to the study of the spatial distribution of archaeological remains within individual deposits, and in particular to faunal assemblages. Despite this, they can prove essential to understanding dispersion and grouping patterns within deposits fully, and, together with various correlation analytical techniques, they provide valuable information about the economic organization of settlements and inhabitant lifeways. To demonstrate the potential of this methodology, a zooarchaeological GIS has been prepared for the Middle and Late Magdalenian and Azilian layers in El Mirón Cave (eastern Cantabria, Spain), and the spatial distribution patterns of various attributes of the archaeological record have been analysed. Significant conclusions in terms of type and duration of human occupation have been drawn. [source] Gap junctional coupling between progenitor cells at the retinal margin of adult goldfishDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Fuminobu Tamalu Abstract We prepared living slice preparations of the peripheral retina of adult goldfish to examine electrical membrane properties of progenitor cells at the retinal margin. Cells were voltage-clamped near resting potential and then stepped to either hyperpolarizing or depolarizing test potentials using whole-cell voltage-clamp recordings. Electrophysiologically examined cells were morphologically identified by injecting both Lucifer Yellow (LY) and biocytin. All progenitor cells examined (n = 37) showed a large amount of passively flowing currents of either sign under suppression of the nonjunctional currents flowing through K+ and Ca2+ channels in the cell membrane. They did not exhibit any voltage-gated Na+ currents. Cells identified by LY fills were typically slender. As the difference between the test potential and the resting potential increased, 13 out of 37 cells exhibited symmetrically voltage- and time-dependent current decline on either sign at the resting potential. The symmetric current profile suggests that the current may be driven and modulated by the junctional potential difference between the clamping cell and its neighbors. The remaining 24 cells did not exhibit voltage dependency. A gap junction channel blocker, halothane, suppressed the currents. A decrease in extracellular pH reduced coupling currents and its increase enhanced them. Dopamine, cAMP, and retinoic acid did not influence coupling currents. Injection of biocytin into single progenitor cells revealed strong tracer coupling, which was restricted in the marginal region. Immature ganglion cells closely located to the retinal margin exhibited voltage-gated Na+ currents. They did not reveal apparent tracer coupling. These results demonstrate that the marginal progenitor cells couple with each other via gap junctions, and communicate biochemical molecules, which may subserve or interfere with cellular differentiation. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 204,214, 2001 [source] Early neural activity and dendritic growth in turtle retinal ganglion cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Vandana Mehta Abstract Early neural activity, both prenatal spontaneous bursts and early visual experience, is believed to be important for dendritic proliferation and for the maturation of neural circuitry in the developing retina. In this study, we have investigated the possible role of early neural activity in shaping developing turtle retinal ganglion cell (RGC) dendritic arbors. RGCs were back-labelled from the optic nerve with horseradish peroxidase (HRP). Changes in dendritic growth patterns were examined across development and following chronic blockade or modification of spontaneous activity and/or visual experience. Dendrites reach peak proliferation at embryonic stage 25 (S25, one week before hatching), followed by pruning in large field RGCs around the time of hatching. When spontaneous activity is chronically blocked in vivo from early embryonic stages (S22) with curare, a cholinergic nicotinic antagonist, RGC dendritic growth is inhibited. On the other hand, enhancement of spontaneous activity by dark-rearing (Sernagor & Grzywacz (1996)Curr. Biol., 6, 1503,1508) promotes dendritic proliferation in large-field RGCs, an effect that is counteracted by exposure to curare from hatching. We also recorded spontaneous activity from individual RGCs labelled with lucifer yellow (LY). We found a tendency of RGCs with large dendritic fields to be spontaneously more active than small-field cells. From all these observations, we conclude that immature spontaneous activity promotes dendritic growth in developing RGCs. [source] Pfkfb3 is transcriptionally upregulated in diabetic mouse liver through proliferative signalsFEBS JOURNAL, Issue 16 2009Joan Duran The ubiquitous isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (uPFK-2), a product of the Pfkfb3 gene, plays a crucial role in the control of glycolytic flux. In this study, we demonstrate that Pfkfb3 gene expression is increased in streptozotocin-induced diabetic mouse liver. The Pfkfb3/-3566 promoter construct linked to the luciferase reporter gene was delivered to the liver via hydrodynamic gene transfer. This promoter was upregulated in streptozotocin-induced diabetic mouse liver compared with transfected healthy cohorts. In addition, increases were observed in Pfkfb3 mRNA and uPFK-2 protein levels, and intrahepatic fructose-2,6-bisphosphate concentration. During streptozotocin-induced diabetes, phosphorylation of both p38 mitogen-activated protein kinase and Akt was detected, together with the overexpression of the proliferative markers cyclin D and E2F. These findings indicate that uPFK-2 induction is coupled to enhanced hepatocyte proliferation in streptozotocin-induced diabetic mouse liver. Expression decreased when hepatocytes were treated with either rapamycin or LY 294002. This shows that uPFK-2 regulation is phosphoinositide 3-kinase,Akt,mammalian target of rapamycin dependent. These results indicate that fructose-2,6-bisphosphate is essential to the maintenance of the glycolytic flux necessary for providing energy and biosynthetic precursors to dividing cells. [source] Pharmacological "cross-inhibition" of connexin hemichannels and swelling activated anion channelsGLIA, Issue 3 2009Zu-Cheng Ye Abstract The study of ion channels has relied heavily on the use of pharmacological blocking agents. However, many of these agents have multiple effects, which may compromise interpretation of results when the affected mechanisms/pathways mediate similar functions. Volume regulated anion channels (VRAC) and connexin hemichannels can both mediate the release of glutamate and taurine, although these channels have distinct activation stimuli and hemichannels, but not VRAC, are permeable to Lucifer Yellow (LY). It has been reported that some anion channel blockers may inhibit connexin hemichannels. We further examined the effects of classic gap junction/hemichannel blockers and anion channel blockers on these channels. The typical VRAC blockers, NPPB, IAA-94, and tamoxifen blocked low divalent cation-induced glutamate and taurine release and LY loading, presumed due to hemichannel opening. The blocking action of these compounds on hemichannels was concentration dependent and fell within the same range where the drugs classically block VRACs. Conversely, carbenoxolone (CBX), the most widely used gap junction/hemichannel blocker, was an effective blocker of VRAC-mediated glutamate and taurine release, and blocked these channels at similar concentrations at which it blocked hemichannels. The CBX effect on VRACs was verified using astrocytes from connexin 43 knock out (Cx43 KO) animals. In these cells, the hypotonic induced amino acid flux was retained whereas the low divalent cation solution-induced flux was lost. These results extend our knowledge about "cross-inhibition" of VRACs and gap junctions/hemichannels by certain pharmacological agents. Given the overlap in function of these two types of channels, great care must be exerted in using pharmacological blockers to identify one channel from the other. © 2008 Wiley-Liss, Inc. [source] DEC-205lo Langerinlo neonatal Langerhans' cells preferentially utilize a wortmannin-sensitive, fluid-phase pathway to internalize exogenous antigenIMMUNOLOGY, Issue 4 2003Bernadette M. Bellette Summary Antigen treatment of neonatal epidermis results in antigen-specific immune suppression. Compared with adult counterparts, neonatal Langerhans' cells (LC) demonstrate an impaired ability to transport antigen to the lymph node (LN). As it is possible that neonatal LC have a reduced ability to endocytose antigen, we evaluated the acquisition of endocytic function, the expression of uptake receptors and the internalization of soluble and small particulate antigens in neonatal, juvenile and adult mice. Although LC from 4-day-old mice were weakly positive for the mannose-type receptor, Langerin, they were capable of internalizing fluorescein isothiocyanate (FITC)-dextran, but to a lesser extent than LC from 6-week-old mice. However, when ratio data were calculated to account for variations in fluorescence intensity at 4°, it was demonstrated that neonatal LC continued to internalize antigen over a longer period of time than adult mice and, as the ratios were much higher, that neonatal cells were also relatively more efficient in antigen uptake. When receptors for mannan and mannose were competitively blocked, LC from neonatal mice, but not adult mice, could still efficiently internalize FITC,dextran. Consequently, the uptake of FITC,dextran, in part, occurred via alternative receptors or a receptor-independent fluid-phase pathway. A feasible pathway is macropinocytosis, as LC from 4-day-old mice demonstrated a reduction in FITC,dextran internalization by the macropinocytosis inhibitor, wortmannin. Evidence of a functional macropinocytosis pathway in neonatal LC was further supported by internalization of the soluble tracer Lucifer Yellow (LY). We conclude that neonatal LC preferentially utilize a wortmannin-sensitive, fluid-phase pathway, rather than receptor-mediated endocytosis, to internalize antigen. As neonatal LC are capable of sampling their environment without inducing immunity, this may serve to avoid inappropriate immune responses during the neonatal period. [source] Phosphorylation by COP9 Signalosome-Associated CK2 Promotes Degradation of p27 during the G1 Cell Cycle PhaseISRAEL JOURNAL OF CHEMISTRY, Issue 2 2006Xiaohua Huang The cell cycle regulator p27Kip1 (p27) is controlled by 26S proteasome-mediated proteolysis by two different pathways. From the S till the G2 phase of the cell cycle, degradation of p27 takes place in the nucleus and is initiated by CDK2-dependent phosphorylation of threonine 187 with subsequent ubiquitination by the SCFSkp2 ubiquitin ligase. During the G1 cell cycle phase (G1), p27 breakdown is cytosolic and is initiated by nuclear export with subsequent ubiquitination by a RING finger ligase called kip1 ubiquitination complex. Here we show that the COP9 signalosome (CSN) is a regulator of p27 proteolysis during G1. The CSN interacts with p27 and the CSN-associated kinase CK2 phosphorylates p27 at two regions. One is central to the protein (amino acids 101,113), and the other was mapped near to the C-terminus (amino acids 170,189). Elimination of the putative C-terminal phosphorylation sites stabilizes ectopic p27 towards proteasomal degradation and abolishes CSN,p27 binding. Inhibition of CSN-associated kinase activity by curcumin attenuates loss of p27 upon cell cycle re-entry. Similar but not additive effects of the phosphoinositol-3-kinase blocker LY 290042 may point to a common pathway of CSN-associated CK2 and protein kinase B/Akt (Akt) in regulating p27 abundance. Akt is found in Flag pulldowns of lysates obtained from cells permanently expressing Flag-tagged CSN2, indicating that Akt is a novel kinase associated with the CSN. Thus, the CSN seems to regulate p27 proteolysis at G1 downstream of Ras-mediated signal pathways. [source] Comparison of total tract digestibility, development of visceral organs and digestive tract of Mong cai and Yorkshire × Landrace piglets fed diets with different fibre sourcesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2009N. T. Len Summary The aim of the study was to evaluate the effects of piglet age and dietary fibre source on the development of visceral organs and the gastrointestinal tract (GIT), and on growth performance and total tract apparent digestibility (TTAD) in local [pure-breed Mong cai (MC)] and exotic [Landrace × Yorkshire (LY)] piglets. The experimental diets contained different fibre sources: C (basal diet), RB (basal diet + rice bran), SPVM (basal diet + sweet potato vine meal) and CReM (basal diet + cassava residue meal). The neutral detergent fibre (NDF) content in diet C and the fibrous diets was 8.8% and 17.1%,17.7% respectively (dry matter basis). Collection of faecal samples to determine TTAD was carried out for five consecutive days before the experiment was finished (63 days). The piglets were killed at the age of 10 days (before being given the same solid feed), 30 days (weaning, 20 days after solid feed introduced) and 63 days (33 days after being given the different fibrous diets) when the length of intestinal segments, weight of organs (liver, heart, kidneys) and empty weight of the GIT (stomach, small intestine, caecum and colon + rectum) were measured. As the age of animals increased, the relative weight of organs and the length of intestines (expressed on a mass-specific basis) decreased (p < 0.05), and the weight of GIT increased (p < 0.001). The piglets fed fibrous diets had heavier GIT than those fed diet C with the highest values in CReM (p < 0.05). The colon + rectum length was not significantly different among C, RB and SPVM, but was shorter than in CReM (p < 0.05). Coefficient of total tract apparent digestibility (CTTAD) of nutrients in the fibrous diets was lower than in C (p < 0.01). Average daily gain (ADG) and feed conversion ratio (FCR) in C, RB and CReM were not different and were better than in SPVM (p < 0.01). There were no significant differences in the weights of organs between the two breeds at day 10, 30 and 63 (p > 0.05). The weight and length of GIT were not significantly different between the two breeds at day 10 and day 30, but were greater for MC at day 63. The caecum and colon + rectum at 10 and 30 days were longer in MC than in LY (p < 0.001). The relative development of GIT post-weaning was higher than pre-weaning, the difference being most apparent in MC. As a result at 63 days, MC had heavier visceral organs and GIT, and longer intestines on fibrous diets than LY (p < 0.05). The MC at 63 days had higher CTTAD of organic matter, gross energy, crude fibre and NDF (p < 0.001) and ether extract and crude protein (p < 0.05), but lower ADG and poorer FCR than LY (p < 0.001). It can be concluded that the GIT of the MC piglets developed more rapidly than LY when they were introduced to solid feed, and that the difference was more marked on the fibrous diets and after weaning, which resulted in higher total tract digestibility of nutrients in MC compared with LY. Cassava residue meal was better digested than RB and SPVM, and supported higher live weight gains. [source] Digestibility and nitrogen retention of diets containing different levels of fibre in local (Mong Cai), F1 (Mong Cai × Yorkshire) and exotic (Landrace × Yorkshire) growing pigs in VietnamJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 7-8 2007N. T. Len Summary Total tract digestibility and nitrogen retention of three diets containing different levels of fibre [200, 260 and 320 g/kg neutral detergent fibre (NDF) in dry matter] were determined in three breeds of growing pig at an initial age of approximately 3.5 months. The breeds were local (Mong Cai, MC), F1 crossbred (MC × Yorkshire) and exotic (Landrace × Yorkshire, LY), allocated at random within breed (block) to double 3 × 3 Latin squares. The main fibrous ingredients of the experimental diets were rice bran, cassava residue meal and non-dehulled groundnut cake meal. Digestibility of organic matter (OM), crude protein (CP), NDF, crude fibre, gross energy (GE) and ether extract (EE) decreased as the level of dietary NDF increased (p < 0.001). The r2 values for the relationship between NDF level and digestibility of OM, CP, GE and EE were 83%, 83%, 80% and 82% respectively. On average, an increase in NDF content of 1% unit resulted in a decrease in OM, CP, GE and EE digestibility of 0.67%, 0.75%, 0.50% and 0.42% units respectively. Digestibility of energy and nutrients was the highest for MC and the lowest for LY (p < 0.01), with intermediate values for F1. There was a negative effect of NDF level on nitrogen (N) retained as a proportion of intake (p < 0.05). Nitrogen retention and utilization were significantly higher (p < 0.001) for LY than for MC and F1 pigs. [source] Oxysterol-induced osteogenic differentiation of marrow stromal cells is regulated by Dkk-1 inhibitable and PI3-kinase mediated signalingJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Christopher M. Amantea Abstract Osteoporosis and its complications cause morbidity and mortality in the aging population, and result from increased bone resorption by osteoclasts in parallel with decreased bone formation by osteoblasts. A widely accepted strategy for improving bone health is targeting osteoprogenitor cells in order to stimulate their osteogenic differentiation and bone forming properties through the use of osteoinductive/anabolic factors. We previously reported that specific naturally occurring oxysterols have potent osteoinductive properties, mediated in part through activation of hedgehog signaling in osteoprogenitor cells. In the present report, we further demonstrate the molecular mechanism(s) by which oxysterols induce osteogenesis. In addition to activating the hedgehog signaling pathway, oxysterol-induced osteogenic differentiation is mediated through a Wnt signaling-related, Dkk-1-inhibitable mechanism. Bone marrow stromal cells (MSC) treated with oxysterols demonstrated increased expression of osteogenic differentiation markers, along with selective induced expression of Wnt target genes. These oxysterol effects, which occurred in the absence of ,-catenin accumulation or TCF/Lef activation, were inhibited by the hedgehog pathway inhibitor, cyclopamine, and/or by the Wnt pathway inhibitor, Dkk-1. Furthermore, the inhibitors of PI3-Kinase signaling, LY 294002 and wortmanin, inhibited oxysterol-induced osteogenic differentiation and induction of Wnt signaling target genes. Finally, activators of canonical Wnt signaling, Wnt3a and Wnt1, inhibited spontaneous, oxysterol-, and Shh-induced osteogenic differentiation of bone marrow stromal cells, suggesting the involvement of a non-canonical Wnt pathway in pro-osteogenic differentiation events. Osteogenic oxysterols are, therefore, important small molecule modulators of critical signaling pathways in pluripotent mesenchymal cells that regulate numerous developmental and post-developmental processes. J. Cell. Biochem. 105: 424,436, 2008. © 2008 Wiley-Liss, Inc. [source] High glucose increase cell cycle regulatory proteins level of mouse embryonic stem cells via PI3-K/Akt and MAPKs signal pathwaysJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2006Yun Hee Kim This study examined the effects of high glucose on cell proliferation and its related signal pathways using mouse embryonic stem (ES) cells. Here, we showed that high glucose level significantly increased [3H]thymidine incorporation, BrdU incorporation, the number of cells, [3H]leucine, and [3H]proline incorporation in a time-(>3 hr) and dose-(>25 mM) dependent manner. Moreover, high glucose level increased the cellular reactive oxygen species (ROS), Akt, and mitogen-activated protein kinases (MAPKs) phosphorylation. Subsequently, these signaling molecules involved in high glucose-induced increase of [3H]thymidine incorporation. High glucose level also increased cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4 protein levels, which is cell cycle regulatory proteins acting in G1,S phase of cell cycle. Inhibition of phosphatidylinositol 3-kinase (PI3-K) (LY 294002: PI3-kinase inhibitor, 10,6 M), Akt (Akt inhibitor, 10,5 M), and p44/42 MAPKs (PD 98059: MEK inhibitor, 10,5 M) decreased these proteins. High glucose level phosphorylated the RB protein, which was decreased by inhibition of PI3-K and Akt. In conclusion, high glucose level stimulates mouse ES cell proliferation via the PI3-K/Akt and MAPKs pathways. J. Cell. Physiol. 209: 94,102, 2006. © 2006 Wiley-Liss, Inc. [source] Reactivity of Tyr,Leu and Leu,Tyr dipeptides: identification of oxidation products by liquid chromatography,tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 5 2009Conceiçăo Fonseca Abstract The exposure of peptides and proteins to reactive hydroxyl radicals results in covalent modifications of amino acid side-chains and protein backbone. In this study we have investigated the oxidation the isomeric peptides tyrosine,leucine (YL) and leucine,tyrosine (LY), by the hydroxyl radical formed under Fenton reaction (Fe2+/H2O2). Through mass spectrometry (MS), high-performance liquid chromatography (HPLC-MS) and electrospray tandem mass spectrometry (HPLC-MSn) measurements, we have identified and characterized the oxidation products of these two dipeptides. This approach allowed observing and identifying a wide variety of oxidation products, including isomeric forms of the oxidized dipeptides. We detected oxidation products with 1, 2, 3 and 4 oxygen atoms for both peptides; however, oxidation products with 5 oxygen atoms were only present in LY. LY dipeptide oxidation leads to more isomers with 1 and 2 oxygen atoms than YL (3 vs 5 and 4 vs 5, respectively). Formation of the peroxy group occurred preferentially in the C -terminal residue. We have also detected oxidation products with double bonds or keto groups, dimers (YL,YL and LY,LY) and other products as a result of cross-linking. Both amino acids in the dipeptides were oxidized although the peptides showed different oxidation products. Also, amino acid residues have shown different oxidation products depending on the relative position on the dipeptide. Results suggest that amino acids in the C -terminal position are more prone to oxidation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Reduced gap junctional intercellular communication and altered biological effects in mouse osteoblast and rat liver oval cell lines transfected with dominant-negative connexin 43MOLECULAR CARCINOGENESIS, Issue 4 2003Brad L. Upham Abstract Gap junctional intercellular communication (GJIC) maintains normal growth and differentiation of cells in a tissue. The intercellular molecules traversing gap junctions are largely unknown, but the molecular weight (MW) cutoff is normally 1200 Da. No differences in dye transfer were observed in normal or vector controls of WB-F344 rat liver epithelial or mouse osteoblastic MC3T3-E1 cells with either Lucifer Yellow (LY) with a MW of 457 Da (LY-457) or LY with a MW of 649 Da (LY-649). Transfection of a dominant negative-connexin 43 (Cx43) gene decreased GJIC (>50%) when LY-649 was used, however, normal GJIC was observed in both cell lines when LY-457 was used. Therefore, the MW cut off in these clones was considerably less than the wild type. The dominant negative clones of the MC3T3-E1 cells exhibited over 90% less alkaline phosphatase (ALPase) activity and calcium deposition after the induction of differentiation. Similarly, dominant negative Cx43 inhibited gene expression of ALPase and bone sialoprotein but not osteocalcin in MC3T3-E1. WB-F344 cells normally exhibit a biphasic response to 12- O -tetradecanoylphorbol-13-acetate (TPA) where inhibition of GJIC recovers after 2 h, but the dominant negative clones showed no recovery from inhibition of GJIC by TPA. Dominant negative Cx43 also inhibited the formation of network-like structures by WB-F344 cells on Matrigel. These results demonstrate that the dominant negative gene transfected into cell types containing the wild-type connexins result in diminished channel sizes, thus allowing the determination of whether distinct biological endpoints, i.e., differentiation, are dependent upon either small or high MW intercellular signals. © 2003 Wiley-Liss, Inc. [source] Endothelin A receptors mediate relaxation of guinea pig internal anal sphincter through cGMP pathwayNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2010S.-c. Huang Abstract Background, Endothelin (ET) modulates motility of the internal anal sphincter through unclear receptor subtypes. Methods, We measured relaxation of guinea pig internal anal sphincter strips caused by ET-related peptides and binding of 125I-ET-1 to cell membranes prepared from the internal anal sphincter muscle. Visualization of 125I-ET-1 binding sites in tissue was performed by autoradiography. Key Results , In the guinea pig internal anal sphincter, ET-1 caused a marked relaxation insensitive to tetrodotoxin, atropine, or ,-conotoxin GVIA. ET-2 was as potent as ET-1. ET-3 caused a mild relaxation. The relative potencies for ETs to cause relaxation were ET-1 = ET-2 > ET-3. The ET-1-induced relaxation was inhibited by BQ-123, an ETA antagonist, but not by BQ-788, an ETB antagonist. These indicate that ETA receptors mediate the relaxation. The relaxant response of ET-1 was attenuated by LY 83583, KT 5823, Rp-8CPT-cGMPS, tetraethyl ammonium, 4-aminopyridine and N(omega)-nitro-l-arginine, but not significantly affected by NG -nitro-l-arginine methyl ester, NG -methyl-l-arginine, charybdotoxin, apamin, KT 5720, and Rp-cAMPS. These suggest the involvement of cyclic guanosine 3,,5,-cyclic monophosphate (cGMP), and potassium channels. Autoradiography localized 125I-ET-1 binding to the internal anal sphincter. Binding of 125I-ET-1 to the cell membranes prepared from the internal anal sphincter revealed the presence of two subtypes of ET receptors, ETA and ETB receptors. Conclusions & Inferences, Taken together, these results demonstrate that ETA receptors mediate relaxation of guinea pig internal anal sphincter through the cGMP pathway. [source] Shear properties of epoxy under high strain rate loadingPOLYMER ENGINEERING & SCIENCE, Issue 4 2010Niranjan K. Naik Shear properties of epoxy LY 556 under high strain rate loading are presented. Torsional Split Hopkinson Bar apparatus was used for the studies in the shear strain rate range of 385,880 per sec. Experimental details, specimen configuration and development, data acquisition, and processing are presented. Shear strength, shear modulus, and ultimate shear strain are presented as a function of shear strain rate. For comparison, studies are presented at quasi-static loading. It is observed that the shear strength at high strain rate is enhanced up to 45% compared with that at quasi-static loading in the range of parameters considered. Further, it is observed that, in the range of parameters considered, the change in shear properties with the change in shear strain rate is not significant. Comparison of torque versus time behavior derived from signals obtained from strain gauges mounted on incident bar and transmitter bar is also presented. POLYM. ENG. SCI., 2010. © 2010 Society of Plastics Engineers [source] Number of Spermatozoa in the Crypts of the Sperm Reservoir at About 24 h After a Low-Dose Intrauterine and Deep Intrauterine Insemination in SowsREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2010P Tummaruk Contents The aim of this study was to investigate the number of spermatozoa in the crypts of the utero-tubal junction (UTJ) and the oviduct of sows approximately 24 h after intrauterine insemination (IUI) and deep intrauterine insemination (DIUI) and compared with that of conventional artificial insemination (AI). Fifteen crossbred Landrace × Yorkshire (LY) multiparous sows were used in the experiment. Transrectal ultrasonography was performed every 4 h to examine the time of ovulation in relation to oestrous behaviour. The sows were inseminated with a single dose of diluted fresh semen by the AI (n = 5), IUI (n = 5) and DIUI (n = 5) at approximately 6,8 h prior to the expected time of ovulation, during the second oestrus after weaning. The sperm dose contained 3000 × 106 spermatozoa in 100 ml for AI, 1,000 × 106 spermatozoa in 50 ml for IUI and 150 × 106 spermatozoa in 5 ml for DIUI. The sows were anaesthetized and ovario-hysterectomized approximately 24 h after insemination. The oviducts and the proximal part of the uterine horns (1 cm) on each side of the reproductive tracts were collected. The section was divided into four parts, i.e. UTJ, caudal isthmus, cranial isthmus and ampulla. The spermatozoa in the lumen in each part were flushed several times with phosphate buffer solution. After flushing, the UTJ and all parts of the oviducts were immersed in a 10% neutral buffered formalin solution. The UTJ and each part of the oviducts were cut into four equal parts and embedded in a paraffin block. The tissue sections were transversely sectioned to a thickness of 5 ,m. Every fifth serial section was mounted and stained with haematoxylin and eosin. The total number of spermatozoa from 32 sections in each parts of the tissue (16 sections from the left side and 16 sections from the right side) was determined under light microscope. The results reveal that most of the spermatozoa in the histological section were located in groups in the epithelial crypts. The means of the total number of spermatozoa in the sperm reservoir (UTJ and caudal isthmus) were 2296, 729 and 22 cells in AI, IUI and DIUI groups, respectively (p < 0.01). The spermatozoa were found on both sides of the sperm reservoir in all sows in the AI and the IUI groups. For the DIUI group, spermatozoa were not found on any side of the sperm reservoir in three out of five sows, found in unilateral side of the sperm reservoir in one sow and found in both sides of the sperm reservoir in one sow. No spermatozoa were found in the cranial isthmus, while only one spermatozoon was found in the ampulla part of a sow in the IUI group. In conclusion, DIUI resulted in a significantly lower number of spermatozoa in the sperm reservoir approximately 24 h after insemination compared with AI and IUI. Spermatozoa could be obtained from both sides of the sperm reservoir after AI and IUI but in one out of five sows inseminated by DIUI. [source] Laminin acts via focal adhesion kinase/phosphatidylinositol-3, kinase/protein kinase B to down-regulate ,1 -adrenergic receptor signalling in cat atrial myocytesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2009Y. G. Wang We previously reported that short-term (2 h) plating of cat atrial myocytes on the extracellular matrix protein, laminin (LMN) decreases adenylate cyclase activity and ,1 -adrenergic receptor (,1 -AR) stimulation of L-type Ca2+ current (ICa,L). The present study sought to determine whether LMN-mediated down-regulation of ,1 signalling is due to down-regulation of adenylate cyclase and to gain insight into the signalling mechanisms responsible. ,1 -AR stimulation was achieved by 0.01 ,m isoproterenol (isoprenaline) plus 0.1 ,m ICI 118551, a selective ,2 -AR antagonist. Atrial myocytes were plated for at least 2 h on uncoated cover-slips (,LMN) or cover-slips coated with LMN (+LMN). As previously reported, ,1 -AR stimulation of ICa,L was significantly smaller in +LMN compared to ,LMN atrial myocytes. In ,LMN myocytes, 10 ,m LY294002 (LY), a specific inhibitor of PI-(3)K, had no effect on ,1 -AR stimulation of ICa,L. In +LMN myocytes, however, LY significantly increased ,1 -AR stimulation of ICa,L. Western blots revealed that compared with ,LMN myocytes, +LMN myocytes showed a significant increase in Akt phosphorylation at Ser-473, which was prevented by LY. In another approach, +LMN myocytes were infected (multiplicity of infection (MOI), 100; 24 h) with replication-defective adenoviruses (Adv) expressing dominant-negative inhibitors of focal adhesion kinase (FAK) (Adv-FRNK or Adv-Y397F-FAK) or Akt (Adv-dnAkt). Compared with control cells infected with Adv-,-galactosidase, cells infected with Adv-FRNK, Adv-Y397F-FAK or Adv-dnAkt each exhibited a significantly greater ,1 -AR stimulation of ICa,L. In ,LMN myocytes LY had no effect on forskolin (FSK)-stimulated ICa,L. However, in +LMN myocytes LY significantly increased FSK-stimulated ICa,L. Similar results were obtained in +LMN atrial myocytes infected with Adv-FRNK. We conclude that LMN binding to ,1 -integrin receptors acts via FAK/PI-(3)K/Akt to inhibit adenylate cyclase activity and thereby down-regulates ,1 -AR-mediated stimulation of ICa,L. These findings provide new insight into the cellular mechanisms by which the extracellular matrix can modulate atrial ,-AR signalling. [source] Silage preparation and nutritive value of Chinese yam by-productANIMAL SCIENCE JOURNAL, Issue 4 2009Chuncheng XU ABSTRACT The objective of this experiment was to determine the ensiling characteristics, nutrient composition and nutritive value of Chinese yam by-product (CYBP) silage treated without additive (Control), with lactic acid bacteria (LY), with dried beet pulp (BY), or with mixtures of lactic acid bacteria and dried beet pulp (LBY) for a fermentation period of 150 days. The nutritive value of CYBP silage was studied in an in vivo digestibility trial using wethers in a 4 × 4 Latin square design. Addition of lactic acid bacteria and/or dried beet pulp greatly improved fermentation quality of CYBP silage. The pH was reduced to below 4.0 and lactic acid was produced at above 4.6% on dry matter basis. There were no statistical differences among treatments in the digestibilities of dry matter, organic matter, crude protein and energy in the silages, but neutral detergent fiber and acid detergent fiber digestibility were higher (P < 0.001) in wethers fed BY and LBY silages compared to the control and LY silages. It was estimated that total digestible nutrient and digestible energy in the CYBP silage averaged 79.1% and 14.3 MJ/kg on dry matter basis. The study suggests that CYBP can be well preserved by making a silage and it is a good potential energy source for ruminant diets. [source] 900 MHz modulated electromagnetic fields accelerate the clathrin-mediated endocytosis pathwayBIOELECTROMAGNETICS, Issue 3 2009Mihaela G. Moisescu Abstract We report new data regarding the molecular mechanisms of GSM-induced increase of cell endocytosis rate. Even though endocytosis represents an important physical and biological event for cell physiology, studies on modulated electromagnetic fields (EMF) effects on this process are scarce. In a previous article, we showed that fluid phase endocytosis rate increases when cultured cells are exposed to 900 MHz EMF similar to mobile phones' modulated GSM signals (217 Hz repetition frequency, 576 µs pulse width) and to electric pulses similar to the GSM electrical component. Trying to distinguish the mechanisms sustaining this endocytosis stimulation, we exposed murine melanoma cells to Lucifer Yellow (LY) or to GSM,EMF/electric pulses in the presence of drugs inhibiting the clathrin- or the caveolin-dependent endocytosis. Experiments were performed at a specific absorption rate (SAR) of 3.2 W/kg in a wire patch cell under homogeneously distributed EMF field and controlled temperature (in the range of 28.5,29.5 °C). Thus, the observed increase in LY uptake was not a thermal effect. Chlorpromazine and ethanol, but not Filipin, inhibited this increase. Therefore, the clathrin-dependent endocytosis is stimulated by the GSM,EMF, suggesting that the cellular mechanism affected by the modulated EMF involves vesicles that detach from the cell membrane, mainly clathrin-coated vesicles. Bioelectromagnetics 30:222,230, 2009. © 2008 Wiley-Liss, Inc. [source] Activation of protein kinase B by the A1 -adenosine receptor in DDT1MF-2 cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000Renée Germack In this study the effect of insulin and A1 -adenosine receptor stimulation on protein kinase B (PKB) activation has been investigated in the hamster vas deferens smooth muscle cell line DDT1MF-2. Increases in PKB phosphorylation were determined by Western blotting using an antibody that detects PKB phosphorylation at Ser473. Insulin, a recognized activator of PKB, stimulated a concentration-dependent increase in PKB phosphorylation in DDT1MF-2 cells (EC50 5±1 pM). The selective A1 -adenosine receptor agonist N6 -cyclopentyladenosine (CPA) stimulated time and concentration-dependent increases in PKB phosphorylation in DDT1MF-2 cells (EC50 1.3±0.5 nM). CPA-mediated increases in PKB phosphorylation were antagonized by the A1 -adenosine receptor selective antagonist 1,3-dipropylcyclopentylxanthine (DPCPX) yielding an apparent KD value of 2.3 nM. Pre-treatment of DDT1MF-2 cells with pertussis toxin (PTX, 100 ng ml,1 for 16 h), to block Gi/Go -dependent pathways, abolished CPA (1 ,M) induced phosphorylation of PKB. In contrast, responses to insulin (100 nM) were resistant to PTX pre-treatment. The phosphatidylinositol 3-kinase (PI-3K) inhibitors wortmannin (IC50 10.3±0.6 nM) and LY 294002 (IC50 10.3±1.2 ,M) attenuated the phosphorylation of PKB elicited by CPA (1 ,M) in a concentration-dependent manner. Wortmannin (30 nM) and LY 294002 (30 ,M) also blocked responses to insulin (100 nM). Removal of extracellular Ca2+ and chelation of intracellular Ca2+ with BAPTA had no significant effect on CPA-induced PKB phosphorylation. Similarly, pretreatment (30 min) with inhibitors of protein kinase C (Ro 31-8220; 10 ,M), tyrosine kinase (genistein; 100 ,M), mitogen-activated protein (MAP) kinase kinase (PD 98059; 50 ,M) and p38 MAPK (SB 203580; 20 ,M) had no significant effect on CPA-induced PKB phosphorylation. In conclusion, these data demonstrate that A1 -adenosine receptor stimulation in DDT1MF-2 cells increases PKB phosphorylation through a PTX and PI-3K-sensitive pathway. British Journal of Pharmacology (2000) 130, 867,874; doi:10.1038/sj.bjp.0703396 [source] The value of medical interventions for lung cancer in the elderly,CANCER, Issue 11 2007Results from SEER-CMHSF Abstract BACKGROUND. Lung cancer is the leading source of cancer mortality and spending. However, the value of spending on the treatment of lung cancer has not been conclusively demonstrated. The authors evaluated the value of medical care between 1983 and 1997 for nonsmall cell lung cancer in the elderly US population. METHODS. The authors used Surveillance, Epidemiology, and End Results (SEER) data to calculate life expectancy after diagnosis over the period 1983 to 1997. Direct costs for nonsmall cell lung cancer detection and treatment were determined by using Part A and Part B reimbursements from the Continuous Medicare History Sample File (CMHSF) data. The CMHSF and SEER data were linked to calculate lifetime treatment costs over the time period of interest. RESULTS. Life expectancy improved minimally, with an average increase of approximately 0.60 months. Total lifetime lung cancer spending rose by approximately $20,157 per patient in real, ie, adjusted for inflation, 2000 dollars from the early 1980s to the mid-1990s, for a cost-effectiveness ratio of $403,142 per life year (LY). The cost-effectiveness ratio was $143,614 for localized cancer, $145,861 for regional cancer, and $1,190,322 for metastatic cancer. CONCLUSIONS. The cost-effectiveness ratio for nonsmall cell lung cancer was higher than traditional thresholds used to define cost-effective care. The most favorable results were for persons diagnosed with early stage cancer. These results suggested caution when encouraging more intensive care for lung cancer patients without first considering the tradeoffs with the costs of this therapy and its potential effects on mortality and/or quality of life. Cancer 2007. © 2007 American Cancer Society. [source] Exercise prevents the effects of experimental arthritis on the metabolism and function of immune cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2010Francisco Navarro Abstract Active lymphocytes (LY) and macrophages (M,) are involved in the pathophysiology of rheumatoid arthritis (RA). Due to its anti-inflammatory effect, physical exercise may be beneficial in RA by acting on the immune system (IS). Thus, female Wistar rats with type II collagen-induced arthritis (CIA) were submitted to swimming training (6 weeks, 5 days/week, 60,min/day) and some biochemical and immune parameters, such as the metabolism of glucose and glutamine and function of LY and M,, were evaluated. In addition, plasma levels of some hormones and of interleukin-2 (IL-2) were also determined. Results demonstrate that CIA increased lymphocyte proliferation (1.9- and 1.7-fold, respectively, in response to concanavalin A (ConA) and lipopolysaccharide (LPS)), as well as macrophage H2O2 production (1.6-fold), in comparison to control. Exercise training prevented the activation of immune cells, induced by CIA, and established a pattern of substrate utilization similar to that described as normal for these cells. Exercise also promoted an elevation of plasma levels of corticosterone (22.2%), progesterone (1.7-fold) and IL-2 (2.6-fold). Our data suggest that chronic exercise is able to counterbalance the effects of CIA on cells of the IS, reinforcing the proposal that the benefits of exercise may not be restricted to aerobic capacity and/or strength improvement. Copyright © 2010 John Wiley & Sons, Ltd. [source] NBD-cholesterol incorporation by rat macrophages and lymphocytes: a process dependent on the activation state of the cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2004Érica P. Portioli Silva Abstract The time-course of incorporation of NBD-cholesterol by macrophages (Ma) and lymphocytes (LY) obtained from untreated and thioglycollate-injected (thio) rats was investigated. NBD-cholesterol incorporation was also examined in Ma obtained from untreated rats and stimulated in vitro by lipopolysaccharide (LPS) and phorbol-myristate acetate (PMA). The same measurement was performed in LY from untreated rats stimulated by addition of LPS and concanavalin A (Con A) into the culture medium. Thio-treated Ma showed high fluorescence intensity after 1,h of incubation with NBD-cholesterol. Ma submitted concomitant to LPS and NBD-cholesterol showed low fluorescence intensity, as well as Ma stimulated with PMA. Ma from untreated and LPS pre-treated rats showed a similar time-course of incorporation. LY from thio-treated rats showed lower incorporation of NBD-cholesterol in comparison to LY from untreated rats. Incorporation was reduced when LPS was added concomitantly with NBD-cholesterol. On the other hand, LY pre-treated with LPS for 48,h showed a very high incorporation of NBD-cholesterol. Con A treatment did not cause a significant effect on NBD-cholesterol incorporation. The findings presented herein led us to conclude that the uptake of NBD-cholesterol by Ma and LY is markedly affected by the activation state of the cells. Copyright © 2003 John Wiley & Sons, Ltd. [source] Evidence that macrophages transfer arachidonic acid and cholesterol to tissues in vivoCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2003C. M. Peres Abstract Our previous studies have shown that [14C]-labelled cholesterol (CHOL) and arachidonic acid (AA) are transferred from macrophages (M,) to lymphocytes (LY) when these cells are co-cultured. In this study, we investigated whether these lipids can be transferred from control and thioglycollate-elicited M, (THIO-elicited M,) to various tissues and organs in vivo. For this purpose, control and THIO-elicited M, were pre-treated with [14C]-AA and [3H]-CHOL and then injected into the jugular vein of adult rats. More than 75% of the radioactivity injected was found in the liver of rats treated with [14C]-AA labelled-M, either control and THIO-stimulated. The radioactivity of [3H]-CHOL labelled M, was transferred mainly to the liver (51% in the control M, and 23% in the thioglycollate M,7) but it was also found in the kidney, lung and spleen. These results support the proposition that the transfer of lipids between cells also occurs in vivo. The full significance of this phenomenon however remains to be elucidated. Copyright © 2003 John Wiley & Sons, Ltd. [source] Cysteinyl leukotrienes and leukotriene B4 mediate vasoconstriction to arginine vasopressin in rat basilar arteryCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2005Cristina C Trandafir Summary 1.,Arginine vasopressin (AVP) has been reported to be involved in the development of cerebral vasospasm after haemorrhage and cerebral oedema following ischaemia. Endogenously produced 5-lipoxygenase metabolites are able to contract isolated endothelium-preserved arterial strips and modulate vascular permeability. The present study addresses the role of 5-lipoxygenase and its products, namely cysteinyl leukotrienes (CysLTs) and leukotriene (LT) B4, in the contraction induced by AVP in rat basilar artery. 2.,Contractile responses to LTD4, LTC4, LTB4 or AVP were assessed in spiral preparations of rat endothelium-intact basilar artery. Contractions to AVP were determined in the absence or presence of 5-lipoxygenase inhibitors or CysLT1 or BLT receptor antagonists. Contractile responses to leukotrienes and AVP are expressed as a percentage of the contraction induced by 80 mmol/L KCl. 3.,Leukotriene D4, LTC4 and LTB4 acted as vasoconstrictor agents in rat basilar artery, causing contractions (all at concentrations of 1 µmol/L) of 42 ± 13, 54 ± 15 and 25 ± 6% of the response to 80 mmol/L KCl, respectively. A concentration,response curve was constructed for AVP over the range 1 pmol/L to 10 nmol/L and an EC50 value of 0.19 ± 0.02 nmol/L (n = 30) was determinted. The presence of the 5-lipoxygenase inhibitors ZM 230487 (10 nmol/L and 0.1 and 1 µmol/L) and AA 861 (1, 3, 10, and 30 µmol/L), the CysLT1 receptor antagonist MK 571 (3, 10 and 30 µmol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30 µmol/L for both) in the organ bath significantly attenuated the contractions induced by AVP in rat basilar artery (P < 0.05). 4.,The experimental results of the present study provide the first evidence for the involvement of CysLTs and LTB4 in the in vitro constriction induced by AVP in rat basilar artery. In the context of previously reported involvement of AVP in the development of cerebral vasospasm and oedema, the present study draws attention to the potential role played by the 5-lipoxygenase pathway in these pathological processes. [source] Rapid detection of six common Mediterranean and three non-Mediterranean ,-thalassemia point mutations by reverse dot blot analysisAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2003Enrica Foglietta Abstract We describe the implementation of reverse dot blot (RDB) hybridization as a rapid nonradioactive method for the identification of six frequent globin gene point mutations in the Mediterranean population: ,Hph,: ,2 IVS I donor site GGTGAGG , GG-----; ,NcoI,: ,2 initiation codon ATG , ACG; ,TSaudi,: ,2Poly A signal AATAA , AATAAG; ,Icaria,: ,2 termination codon TAA , AAA (Ter , LYS); ,CS,: ,2 termination codon TAA , CAA (Ter , gly); ,,NcoI: ,1 initiation codon ATG , GTG; and three ,2 globin gene point mutations found in immigrants in Italy: ,T-Quongsze,: ,2 codon 12 CTG , CCG (Leu , Pro); ,Seal Rock,: ,2 termination codon TAA , GAA (TER , GLU); and ,Koyadora,: ,2 termination codon TAA , TCA (TER , SER). The method uses the principle of allele-specific oligonucleotide (ASO) hybridization, but it is a nonradioactive method and permits rapid and simultaneous typing of point mutations and small deletions. Am. J. Hematol. 74:191,195, 2003. © 2003 Wiley-Liss, Inc. [source] RNA Grooves Can Accommodate Disulfide-Bridged Bundles of ,-Helical PeptidesCHEMBIOCHEM, Issue 6 2010Soonsil Hyun Dr. Feelin' groovy: A strategy for chemical stapling increases structural as well as chemical stability of helical peptides. Using an amphiphilic peptide with Leu/Lys, two Leu residues were replaced by Cys. Helical bundle peptides were generated by oxidative disulfide bond formation. One of these has a Kd as low as 21 pM against hairpin targets. This observation demonstrates that the groove in small hairpin RNA has sufficient room to contain a helical bundle peptide. [source] What Lies Behind Income Mobility?ECONOMICA, Issue 282 2004Distributional Change in Belgium, Reranking, Western Germany, the USA The paper presents a decomposition of income mobility indices into two basic sources: mobility induced by a change of the income distribution shape, and mobility induced by a reordering of individuals in the income pecking order. The decomposition procedure, based on counterfactual distributions, results in a decomposition that is applicable to a broad class of mobility measures. Application to income ,movement' indices with data for Belgium, Western Germany and the USA indicates that reranking has been the major force behind income mobility. [source] Telling More: Lies, Secrets, and HistoryHISTORY AND THEORY, Issue 4 2000Luise White This essay argues that secrets and lies are not forms of withholding information but forms by which information is valorized. Lies are constructed: what is to be lied about, what a lie is to consist of, how it is to be told, and whom it is to be told to, all reveal a social imaginary about who thinks what and what constitutes credibility. Secrets are negotiated: continual decisions about whom to tell, how much to tell, and whom not to tell describe social worlds, and the shape and weight of interactions therein. All of this makes lies and secrets extraordinarily rich historical sources. We might not see the truth distorted by a lie or the truth hidden by a secret, but we see the ideas andimaginings by which people disclose what should not be made public, and how they should carry out concealing one narrative with another. Such insights involve a step back from the project of social history, in which an inclusive social narrative is based on experience and individuals' ability to report it with some reliability, and suggests that historians need to look at social imaginings as ways to understand the ideas and concerns about which people lie and with which people construct new narratives that are not true. The study of secrets, however, links the study of social imaginings with the project of social history, as the valorization of information that results in the continual negotiation and renegotiation of secrets shows individuals and publics imagining the experiences labeled as secret because of the imagined power of a specific version of events. [source] | |||||||||||||||||||||||||||||||||||||||||||