WorldWideScience

Sample records for inositol lipid turnover

  1. Inositol lipid turnover and compartmentation in canine trachealis smooth muscle

    International Nuclear Information System (INIS)

    Baron, C.B.; Pring, M.; Coburn, R.F.

    1989-01-01

    We established conditions for the study of metabolism and compartmentation of inositol phospholipids in canine trachealis muscle. Unstimulated muscle was incubated with myo-[3H]inositol for 30 min at 37 degrees C which resulted in labeling of the tissue free myo-inositol pool, whereas only a small amount of radioactivity was incorporated into inositol phospholipids or inositol phosphates. After addition of 5.5 microM carbachol, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2), specific radioactivities increased exponentially, reaching apparent constant values in 180-240 min. Initial rates of increases in PI, PIP, and PIP2 specific radioactivities were 39, 32, and 66 times that measured in unstimulated muscle. Metabolic flux rates (nmol.100 nmol total lipid Pi-1.min-1) during development of force averaged 0.42 +/- 0.09 and during force maintenance averaged 0.14 +/- 0.01. Fractions of total PI, PIP, and PIP2 pools that were linked to muscarinic cholinergic activation were estimated to be 0.97, 0.85, and 0.65, respectively. Initial rates of increase in specific radioactivities and specific radioactivities during carbachol activation were similar in PI, PIP, and PIP2 fast active compartments, suggesting metabolic flux from PI to PIP to PIP2 was in near chemical equilibrium. Turnover times for PI, PIP, and PIP2 fast active compartments were estimated to be 21, 1.6, and 4.0 min, respectively

  2. Carbamoylcholine and gastrin induce inositol lipid turnover in canine gastric parietal cells

    International Nuclear Information System (INIS)

    Chiba, T.; Fisher, S.K.; Park, J.; Seguin, E.B.; Agranoff, B.W.; Yamada, Tadataka

    1988-01-01

    The potential role of inositol phospholipid turnover in mediating acid secretion was examined in a preparation enriched for isolated canine gastric parietal cells. The stimulatory effects of carbamoylcholine (carbachol) and gastrin on parietal cell uptake of [ 14 C]aminopyrine were linked to dose- and time-dependent selective reduction in cellular phosphatidylinositol content, although the specific fatty acid composition of the phosphoinositides was not altered. Analysis of [ 3 H]inositol phosphates accumulated in cells prelabeled with [ 3 H]inositol revealed an increase in labeled inositol trisphosphate by 5 min of incubation with either carbachol or gastrin. Furthermore, after preincubation of parietal cells in medium containing [ 32 P]orthophosphate, the two secretagogues elicited a time-dependent decrease in 32 P labeling of phosphatidylinositol 4,5-bisphosphate and concomitant increase in labeling of phosphatidic acid. These data demonstrate that the acid secretagogue actions of carbachol and gastrin are correlated with turnover of cellular inositol phospholipids in a preparation consisting predominantly of parietal cells

  3. Effects of inositol starvation on the levels of inositol phosphates and inositol lipids in Neurospora crassa.

    OpenAIRE

    Lakin-Thomas, P L

    1993-01-01

    An inositol-requiring strain of Neurospora crassa was labelled during growth in liquid medium with [3H]inositol, and the levels of inositol phosphates and phosphoinositides were determined under inositol-sufficient and inositol-starved conditions. Because the mutant has an absolute requirement for inositol, the total mass of inositol-containing compounds could be determined. Inositol-containing lipids were identified by deacylation and co-migration with standards on h.p.l.c.; PtdIns3P, PtdIns...

  4. A short history of inositol lipids

    Science.gov (United States)

    Irvine, Robin F.

    2016-01-01

    The diverse family of inositol lipids is now known to be central to many aspects of cell biology. The route from the first discovery of inositol to our present day knowledge of inositol lipids spans more than 150 years and is long and complex. This is a brief account of some of the most important stages along that route. PMID:27623846

  5. Early effects of Escherichia coli endotoxin infusion on vasopressin-stimulated breakdown and metabolism of inositol lipids in rat hepatocytes

    International Nuclear Information System (INIS)

    Rodriguez de Turco, E.B.; Spitzer, J.A.

    1988-01-01

    The turnover of vasopressin-stimulated 32P-phosphoinositides and 32P-phosphatidic acid and accumulation of [2-3H]-inositol phosphates were examined in hepatocytes from rats infused i.v. with saline and E. coli endotoxin for 3 hrs. Within 60s of VP stimulation the decrease in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate labeling as well as the increased uptake of 32P into phosphatidic acid were similar in both groups. However, at a later time (300s) the 32P-phosphatidylinositol turnover was greatly decreased concomitantly with a higher labeling of phosphatidic acid. The accumulation of [2-3H]-inositol phosphates in ET-cells was significantly decreased both at 30s and 600s after VP addition. The distribution of [2-3H]-inositol labeling accumulated in the different inositol phosphate fractions over the first 30s of VP stimulation showed a tendency to lower accumulation of inositol trisphosphate, and a significantly lower accumulation of inositol bisphosphate simultaneously with a higher labeling of the inositol tetrakisphosphate fraction. These observations reflect an early effect of ET-infusion on VP-stimulated inositol lipid turnover and on the subsequent metabolism of the released inositol phosphates

  6. Inositol lipid metabolism in vasopressin stimulated hepatocytes from rats infused with tumor necrosis factor

    International Nuclear Information System (INIS)

    Spitzer, J.A.; Rodriguez de Turco, E.B.

    1989-01-01

    We studied the effect of i.v. infusion of human recombinant tumor necrosis factor alpha (rHuTNF alpha, Cetus, 15 micrograms/100 g bw over 3 h) on vasopressin (VP)-stimulated 32 P-inositol lipid turnover and the release of 3 H-inositol phosphates in isolated rat hepatocytes. The early VP-induced decrease (within 30 s) in 32 P-phosphatidylinositol 4-phosphate and 32 P-phosphatidylinositol 4,5-bisphosphate labeling was significantly reduced (-40%) and at the same time the uptake of 32 P into phosphatidic acid was 50% lower than in saline-infused (matched control) rats. Within 5 min of VP-stimulation, lower 32 P phosphatidylinositol (-40%) and higher 32 P-phosphatidic acid (+30%) labeling were observed in rHuTNF alpha-infused rats. Infusion of rHuTNF alpha also affected the VP-induced release of 3 H-inositol phosphates. The accumulation of 3 H-inositol-labeled water soluble products was decreased by 25% and 17% at 30 s and 10 min, respectively. These data show that rHuTNF alpha mimics early perturbations induced by Escherichia coli endotoxin infusion in VP-stimulated inositol lipid metabolism in rat hepatocytes

  7. Serotonergic agonists stimulate inositol lipid metabolism in rabbit platelets

    International Nuclear Information System (INIS)

    Schaechter, M.; Godfrey, P.P.; Minchin, M.C.W.; McClue, S.J.; Young, M.M.

    1985-01-01

    The metabolism of inositol phospholipids in response to serotonergic agonists was investigated in rabbit platelets. In platelets prelabelled with [ 3 H]-inositol, in a medium containing 10 mM LiCl which blocks the enzyme inositol-1-phosphatase, 5-hydroxytryptamine (5-HT) caused a dose-dependent accumulation of inositol phosphates (IP). This suggests a phospholipase-C-mediated breakdown of phosphoinositides. Ketanserin, a selective 5-HT 2 antagonist, was a potent inhibitor of the 5-HT response, with a Ki of 28 nM, indicating that 5-HT is activating receptors of the 5-HT 2 type in the platelet. Lysergic acid diethylamide (LSD) and quipazine also caused dose-related increases in inositol phosphate levels, though these were considerably less than those produced by 5-HT. These results show that relatively small changes in phosphoinositide metabolism induced by serotonergic agonists can be investigated in the rabbit platelet, and this cell may therefore be a useful model for the study of some 5-HT receptors. 30 references, 4 figures

  8. No turnover in lens lipids for the entire human lifespan.

    Science.gov (United States)

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger J W

    2015-03-11

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

  9. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders.

    Directory of Open Access Journals (Sweden)

    Eva C Schulte

    Full Text Available Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS and Parkinson`s disease (PD represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases.456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls.After stringent quality control, we identified decreased levels of long-chain (polyunsaturated fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9 and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32. In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7. The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD.A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention.

  10. Cyclic nucleotide regulation of inositol lipid metabolism in rat cerebral cortex

    International Nuclear Information System (INIS)

    Nicchitta, C.V.; Williamson, J.R.

    1986-01-01

    The authors have investigated the effects of compounds known to elevate cAMP levels and/or activate the cAMP dependent protein kinase on resting and stimulated inositol lipid metabolism in rat cortical slices and synaptosomes. In [ 3 H]-myo-inositol-labeled brain slices, carbamylcholine-stimulated accumulation of [ 3 H]-myo-inositol 1-phosphate (IP 1 ) was decreased 50% by forskolin (150μM) isobutylmethylxantihine (IBMX) (1mM), 8-bromo cAMP (5mM) or 8-(4-chlorophenylthio) cAMP (5mM). In studies with synaptosomes, the incorporation of [ 32 Pi] into phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and phosphatidic acid (PA) was also reduced in the presence of forskolin or the cAMP phosphodiesterase inhibitors IBMX and RO20-1724 (+/-)-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone. In the presence of maximally effective concentrations of these agents, steady state PIP levels were reduced by 50% and PIP 2 and PA levels by 40%. The effects of these compounds on [ 32 Pi] labeling of the phosphoinositides and PA are consistent with an inhibition of flux through the inositide cycle, presumably through the action of cAMP. Such an inhibition may account for the reduction in carbamylcholine sensitive IP 1 accumulation observed in brain slices. These studies indicate that in rat brain, β-adrenergic stimulation may be involved in modulating the activity of muscarinic cholinergic agonists. This regulation appears to be at the level of inositol lipid metabolism

  11. Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation of Blebbing.

    Directory of Open Access Journals (Sweden)

    Tatsuroh Sugiyama

    Full Text Available Cells migrate by extending pseudopods such as lamellipodia and blebs. Although the signals leading to lamellipodia extension have been extensively investigated, those for bleb extension remain unclear. Here, we investigated signals for blebbing in Dictyostelium cells using a newly developed assay to induce blebbing. When cells were cut into two pieces with a microneedle, the anucleate fragments vigorously extended blebs. This assay enabled us to induce blebbing reproducibly, and analyses of knockout mutants and specific inhibitors identified candidate molecules that regulate blebbing. Blebs were also induced in anucleate fragments of leukocytes, indicating that this assay is generally applicable to animal cells. After cutting, microtubules in the anucleate fragments promptly depolymerized, followed by the extension of blebs. Furthermore, when intact cells were treated with a microtubule inhibitor, they frequently extended blebs. The depolymerization of microtubules induced the delocalization of inositol lipid phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs. From these observations, we propose a model in which microtubules play a critical role in bleb regulation via inositol lipid metabolism.

  12. Hepatitis C Virus Core Protein Decreases Lipid Droplet Turnover

    Science.gov (United States)

    Harris, Charles; Herker, Eva; Farese, Robert V.; Ott, Melanie

    2011-01-01

    Steatosis is a frequent complication of hepatitis C virus infection. In mice, this condition is recapitulated by the expression of a single viral protein, the nucleocapsid core. Core localizes to the surface of lipid droplets (LDs) in infected liver cells through a process dependent on host diacylglycerol acyltransferase 1 (DGAT1), an enzyme that synthesizes triglycerides in the endoplasmic reticulum. Whether DGAT1 also plays a role in core-induced steatosis is uncertain. Here, we show that mouse embryonic fibroblasts isolated from DGAT1−/− mice are protected from core-induced steatosis, as are livers of DGAT1−/− mice expressing core, demonstrating that the steatosis is DGAT1-dependent. Surprisingly, core expression did not increase DGAT1 activity or triglyceride synthesis, thus excluding the possibility that core activates DGAT1 to cause steatosis. Instead, we find that DGAT1-dependent localization of core to LDs is a prerequisite for the steatogenic properties of the core. Using biochemical and immunofluorescence microscopy techniques, we show that the turnover of lipids in core-coated droplets is decreased, providing a physiological mechanism for core-induced steatosis. Our results support a bipartite model in which core first requires DGAT1 to gain access to LDs, and then LD-localized core interferes with triglyceride turnover, thus stabilizing lipid droplets and leading to steatosis. PMID:21984835

  13. Retinoic acid-induced granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by downregulation of autonomous generation of inositol lipid-derived second messengers

    International Nuclear Information System (INIS)

    Porfiri, E.; Hoffbrand, A.V.; Wickremasinghe, R.G.

    1991-01-01

    Inositol phosphates (InsPs) and diacyglycerol (DAG) are second messengers derived via the breakdown of inositol phospholipids, and which play important signalling roles in the regulation of proliferation of some cell types. The authors have studied the operation of this pathway during the early stages of retionic acid (RA)-induced granulocytic differentiation of HL60 myeloid leukemia cells. The autonomous breakdown of inositol lipids that occurred in HL60 cells labeled with [3H] inositol was completely abolished following 48 hours of RA treatment. The rate of influx of 45Ca2+ was also significantly decreased at 48 hours, consistent with the role of inositol lipid-derived second messengers in regulating Ca2+ entry into cells. The downregulation of inositol lipid metabolism clearly preceded the onset of reduced proliferation induced by RA treatment, and was therefore not a consequence of decreased cell growth. The generation of InsPs in RA-treated cells was reactivated by the fluoroaluminate ion, a direct activator of guanine nucleotide-binding protein(s) (G proteins) that regulate the inositol lipid signalling pathway. Subtle alterations to a regulatory mechanism may therefore mediate the RA-induced downregulation of this pathway. The data are consistent with the hypothesis that the autonomous generation of inositol lipid-derived second messengers may contribute to the continuous proliferation of HL60 cells, and that the RA-induced downregulation of this pathway may, in turn, play a role in signalling the cessation of proliferation that preceedes granulocytic differentiation

  14. Inhibition of polyphosphoinositide turnover in rat cerebral cortex by clonidine

    International Nuclear Information System (INIS)

    Dyck, L.E.

    1989-01-01

    In the rat brain, a number of receptors are linked to phospholipase C which catalyzes the hydrolysis of membrane inositol phospholipids; stimulation of α 1 -adrenergic receptors, for example, increases polyphosphoinositide turnover, but stimulation of α 2 -receptors does not. The hydrolysis of inositol phospholipids in rat cortical slices was investigated using a direct assay involving prelabeling these lipids with 3 H-inositol and then measuring the formation of 3 H-inositol phosphates in the presence of lithium ions. As expected, clonidine, an α 2 -agonist, did not stimulate the formation of 3 H-inositol phosphates; however, clonidine antagonized the ability of noradrenaline to stimulate 3 H-inositol phosphate formation. This effect was not blocked by antagonists of α 2 , 5HT 2 , H 2 , or muscarinic receptors. Clonidine did not affect carbachol-stimulated 3 H-inositol phosphate formation

  15. Regulation of lipid droplet turnover by ubiquitin ligases

    Directory of Open Access Journals (Sweden)

    Rotin Daniela

    2010-07-01

    Full Text Available Abstract Mutation of the protein spartin is a cause of one form of spastic paraplegia. Spartin interacts with ubiquitin ligases of the Nedd4 family, and a recent report in BMC Biology now shows that it acts as an adaptor to recruit and activate the ubiquitin ligase AIP4 onto lipid droplets, leading to the ubiquitination and degradation of droplet-associated proteins. A deficiency of spartin apparently causes lipid droplets to accumulate. See research article: http://www.biomedcentral.com/1741-7007/8/72/

  16. Turnover of lipids labeled by I-123 phenylpentadecanoic acid (IP) compared to C-14 palmitic acid (P)

    International Nuclear Information System (INIS)

    Reske, S.N.; Sauer, W.; Breull, W.; Machulla, H.J.; Winkler, C.

    1984-01-01

    IP has been proposed for evaluation of cardiac lipid metabolism. To elucidate the metabolic fate of IP in more detail, the authors compared its uptake and turnover to that of P in lipids extracted from heart, lung, liver, spleen and kidneys of fasted anaesthetized Wistar rats after simultaneous i.v. tracer injection. The animals were sacrificed at different time intervals until 30 min. p.i. The organs were removed and lipids were extracted with chloroform/methanol. Fractional radioactivity distribution in lipids was analyzed by TLC. I-123 and C-14 radioactivity was assayed in free fatty acid (FFFA)-, phospholipid (PL)-, diglyceride (DG)-, and triglyceride (TG)-fraction in a -spectrometer and 20 weeks later in a liquid scintillation counter. Uptake and turnover patterns of IP-and P-labeled lipids were nearly identical. The authors conclude that IP and P label essentially the same lipids and exhibit very similar lipid turnover characteristics, indicating the feasibility of metabolic studies by means of IP as tracer for lipid metabolism

  17. Turnover of microbial lipids in the deep biosphere and growth of benthic archaeal populations.

    Science.gov (United States)

    Xie, Sitan; Lipp, Julius S; Wegener, Gunter; Ferdelman, Timothy G; Hinrichs, Kai-Uwe

    2013-04-09

    Deep subseafloor sediments host a microbial biosphere with unknown impact on global biogeochemical cycles. This study tests previous evidence based on microbial intact polar lipids (IPLs) as proxies of live biomass, suggesting that Archaea dominate the marine sedimentary biosphere. We devised a sensitive radiotracer assay to measure the decay rate of ([(14)C]glucosyl)-diphytanylglyceroldiether (GlcDGD) as an analog of archaeal IPLs in continental margin sediments. The degradation kinetics were incorporated in model simulations that constrained the fossil fraction of subseafloor IPLs and rates of archaeal turnover. Simulating the top 1 km in a generic continental margin sediment column, we estimated degradation rate constants of GlcDGD being one to two orders of magnitude lower than those of bacterial IPLs, with half-lives of GlcDGD increasing with depth to 310 ky. Given estimated microbial community turnover times of 1.6-73 ky in sediments deeper than 1 m, 50-96% of archaeal IPLs represent fossil signals. Consequently, previous lipid-based estimates of global subseafloor biomass probably are too high, and the widely observed dominance of archaeal IPLs does not rule out a deep biosphere dominated by Bacteria. Reverse modeling of existing concentration profiles suggest that archaeal IPL synthesis rates decline from around 1,000 pg⋅mL(-1) sediment⋅y(-1) at the surface to 0.2 pg⋅mL(-1)⋅y(-1) at 1 km depth, equivalent to production of 7 × 10(5) to 140 archaeal cells⋅mL(-1) sediment⋅y(-1), respectively. These constraints on microbial growth are an important step toward understanding the relationship between the deep biosphere and the carbon cycle.

  18. Maternal obesity modulates intracellular lipid turnover in the human term placenta.

    Science.gov (United States)

    Hirschmugl, B; Desoye, G; Catalano, P; Klymiuk, I; Scharnagl, H; Payr, S; Kitzinger, E; Schliefsteiner, C; Lang, U; Wadsack, C; Hauguel-de Mouzon, S

    2017-02-01

    Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g -1 , Pwomen. Among target genes examined, six showed positive correlation (Pobese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, Ptreatment of cultured trophoblast cells. Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.

  19. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-123I-phenyl-)pentadecanoic and 1-14C-palmitic acid

    International Nuclear Information System (INIS)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C.; Machulla, H.J.; Knust, E.J.

    1984-01-01

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p- 123 I-phenyl-)pentadecanoic and 1- 14 C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. (author)

  20. Synaptotagmin 1 causes phosphatidyl inositol lipid-dependent actin remodeling in cultured non-neuronal and neuronal cells

    International Nuclear Information System (INIS)

    Johnsson, Anna-Karin; Karlsson, Roger

    2012-01-01

    Here we demonstrate that a dramatic actin polymerizing activity caused by ectopic expression of the synaptic vesicle protein synaptotagmin 1 that results in extensive filopodia formation is due to the presence of a lysine rich sequence motif immediately at the cytoplasmic side of the transmembrane domain of the protein. This polybasic sequence interacts with anionic phospholipids in vitro, and, consequently, the actin remodeling caused by this sequence is interfered with by expression of a phosphatidyl inositol (4,5)-bisphosphate (PIP2)-targeted phosphatase, suggesting that it intervenes with the function of PIP2-binding actin control proteins. The activity drastically alters the behavior of a range of cultured cells including the neuroblastoma cell line SH-SY5Y and primary cortical mouse neurons, and, since the sequence is conserved also in synaptotagmin 2, it may reflect an important fine-tuning role for these two proteins during synaptic vesicle fusion and neurotransmitter release.

  1. Structure-Based Design of an Organoruthenium Phosphatidyl-inositol-3-Kinase Inhibitor Reveals a Switch Governing Lipid Kinase Potency and Selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Xie,P.; Williams, D.; Atilla-Gokcumen, G.; Milk, L.; Xiao, M.; Smalley, K.; Herlyn, M.; Meggers, E.; Marmorstein, R.

    2008-01-01

    Mutations that constitutively activate the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, including alterations in PI3K, PTEN, and AKT, are found in a variety of human cancers, implicating the PI3K lipid kinase as an attractive target for the development of therapeutic agents to treat cancer and other related diseases. In this study, we report on the combination of a novel organometallic kinase inhibitor scaffold with structure-based design to develop a PI3K inhibitor, called E5E2, with an IC50 potency in the mid-low-nanomolar range and selectivity against a panel of protein kinases. We also show that E5E2 inhibits phospho-AKT in human melanoma cells and leads to growth inhibition. Consistent with a role for the PI3K pathway in tumor cell invasion, E5E2 treatment also inhibits the migration of melanoma cells in a 3D spheroid assay. The structure of the PI3K?/E5E2 complex reveals the molecular features that give rise to this potency and selectivity toward lipid kinases with implications for the design of a subsequent generation of PI3K-isoform-specific organometallic inhibitors.

  2. Rhizosphere bacterial carbon turnover is higher in nucleic acids than membrane lipids: implications for understanding soil carbon cycling

    Directory of Open Access Journals (Sweden)

    Ashish A. Malik

    2015-04-01

    Full Text Available Using a pulse-chase 13CO2 plant labeling experiment we compared the flow of plant carbon into macromolecular fractions of root-associated soil microorganisms. Time dependent 13C dilution patterns in microbial cellular fractions were used to calculate their turnover time. The turnover times of microbial biomolecules were found to vary: microbial RNA (19 h and DNA (30 h turned over fastest followed by chloroform fumigation extraction-derived soluble cell lysis products (14 d, while phospholipid fatty acids (PLFAs had the slowest turnover (42 d. PLFA/NLFA 13C analyses suggest that both mutualistic arbuscular mycorrhizal and saprophytic fungi are dominant in initial plant carbon uptake. In contrast, high initial 13C enrichment in RNA hints at bacterial importance in initial C uptake due to the dominance of bacterial derived RNA in total extracts of soil RNA. To explain this discrepancy, we observed low renewal rate of bacterial lipids, which may therefore bias lipid fatty acid based interpretations of the role of bacteria in soil microbial food webs. Based on our findings, we question current assumptions regarding plant-microbe carbon flux and suggest that the rhizosphere bacterial contribution to plant assimilate uptake could be higher. This highlights the need for more detailed quantitative investigations with nucleic acid biomarkers to further validate these findings.

  3. PAH1-encoded phosphatidate phosphatase plays a role in the growth phase- and inositol-mediated regulation of lipid synthesis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Pascual, Florencia; Soto-Cardalda, Aníbal; Carman, George M

    2013-12-13

    In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids in the exponential phase of growth occurs at the expense of the storage lipid triacylglycerol. As exponential phase cells progress into the stationary phase, the synthesis of triacylglycerol occurs at the expense of phospholipids. Early work indicates a role of the phosphatidate phosphatase (PAP) in this metabolism; the enzyme produces the diacylglycerol needed for the synthesis of triacylglycerol and simultaneously controls the level of phosphatidate for the synthesis of phospholipids. Four genes (APP1, DPP1, LPP1, and PAH1) encode PAP activity in yeast, and it has been unclear which gene is responsible for the synthesis of triacylglycerol throughout growth. An analysis of lipid synthesis and composition, as well as PAP activity in various PAP mutant strains, showed the essential role of PAH1 in triacylglycerol synthesis throughout growth. Pah1p is a phosphorylated enzyme whose in vivo function is dependent on its dephosphorylation by the Nem1p-Spo7p protein phosphatase complex. nem1Δ mutant cells exhibited defects in triacylglycerol synthesis and lipid metabolism that mirrored those imparted by the pah1Δ mutation, substantiating the importance of Pah1p dephosphorylation throughout growth. An analysis of cells bearing PPAH1-lacZ and PPAH1-DPP1 reporter genes showed that PAH1 expression was induced throughout growth and that the induction in the stationary phase was stimulated by inositol supplementation. A mutant analysis indicated that the Ino2p/Ino4p/Opi1p regulatory circuit and transcription factors Gis1p and Rph1p mediated this regulation.

  4. Role of inositol phospholipids in the action of calcemic hormones on bone

    International Nuclear Information System (INIS)

    Rappaport, M.S.

    1986-01-01

    Phosphatidylinositol (Ptdlns) and its metabolites are suspected of having a critical role in cellular signaling by hormonal agents. Parathyroid hormone (PTH) in particular has been shown to alter Ptdlns turnover in kidney preparations. In bone, PTH and other calcemic hormones affect the degree and extent of mineralization. The mechanism of bone resorption by these agents was studied in relation to the activity of the Ptdlns metabolic cycle. Inositol was transported into newborn mouse calvaria linearly over 5 to 120 minutes and was incorporated into three phospholipids: Ptdlns (95.1%), Ptdlns-4-P (2.8%), and Ptdlns-4,5-P 2 (2.2%). PTH (0.1 U/ml) increased Ptdlns labeling by 3 H-inositol after 2, 6, and 24 h of hormone treatment. PTH had no effect on 32 P labeling of lipids other than Ptdlns. In fetal rat limb bones, inositol transport was linear and unaltered by PTH of calcitonin (sCT); 3 H-inositol labeled Ptdlns, Ptdlns-4-P, and Ptdlns-4,5-P 2 in proportions similar to that found in mouse calvaria. PTH (0.1-100 nM) stimulated inositol incorporation into Ptdlns after 2 and 24 h treatment. This effect was dependent on functional molecule, since oxidized PTH did not stimulate Ptdins labeling. sCT alone (1-100 nM) inhibited labeling after 24 h and inhibited PTH-stimulated labeling at 2 and 24 h. The data suggest that the observed enhancement in Ptdlns metabolism has physiological significance. It is concluded that inositol-containing phospholipids have a functional role in the action of PTH and sCT on bone tissue

  5. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

    Directory of Open Access Journals (Sweden)

    L.B. Oliveros

    2004-03-01

    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  6. Inositol synthesis regulates the activation of GSK-3α in neuronal cells.

    Science.gov (United States)

    Ye, Cunqi; Greenberg, Miriam L

    2015-04-01

    The synthesis of inositol provides precursors of inositol lipids and inositol phosphates that are pivotal for cell signaling. Mood stabilizers lithium and valproic acid, used for treating bipolar disorder, cause cellular inositol depletion, which has been proposed as a therapeutic mechanism of action of both drugs. Despite the importance of inositol, the requirement for inositol synthesis in neuronal cells is not well understood. Here, we examined inositol effects on proliferation of SK-N-SH neuroblastoma cells. The essential role of inositol synthesis in proliferation is underscored by the findings that exogenous inositol was dispensable for proliferation, and inhibition of inositol synthesis decreased proliferation. Interestingly, the inhibition of inositol synthesis by knocking down INO1, which encodes inositol-3-phosphate synthase, the rate-limiting enzyme of inositol synthesis, led to the inactivation of GSK-3α by increasing the inhibitory phosphorylation of this kinase. Similarly, the mood stabilizer valproic acid effected transient decreases in intracellular inositol, leading to inactivation of GSK-3α. As GSK-3 inhibition has been proposed as a likely therapeutic mechanism of action, the finding that inhibition of inositol synthesis results in the inactivation of GSK-3α suggests a unifying hypothesis for mechanism of mood-stabilizing drugs. Inositol is an essential metabolite that serves as a precursor for inositol lipids and inositol phosphates. We report that inhibition of the rate-limiting enzyme of inositol synthesis leads to the inactivation of glycogen synthase kinase (GSK) 3α by increasing inhibitory phosphorylation of this kinase. These findings have implications for the therapeutic mechanisms of mood stabilizers and suggest that inositol synthesis and GSK 3α activity are intrinsically related. © 2014 International Society for Neurochemistry.

  7. Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion

    DEFF Research Database (Denmark)

    Ferreira, Raphael; Teixeiraa, Paulo Goncalves; Siewers, Verena

    2018-01-01

    Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex...... and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid...

  8. Inositol synthesis regulates activation of GSK-3α in neuronal cells

    Science.gov (United States)

    Ye, Cunqi; Greenberg, Miriam L.

    2015-01-01

    The synthesis of inositol provides precursors of inositol lipids and inositol phosphates that are pivotal for cell signaling. Mood-stabilizers lithium and valproic acid (VPA), used for treating bipolar disorder, cause cellular inositol depletion, which has been proposed as a therapeutic mechanism of action of both drugs. Despite the importance of inositol, the requirement for inositol synthesis in neuronal cells is not well understood. Here, we examined inositol effects on proliferation of SK-N-SH neuroblastoma cells. The essential role of inositol synthesis in proliferation is underscored by the findings that exogenous inositol was dispensable for proliferation, and inhibition of inositol synthesis decreased proliferation. Interestingly, the inhibition of inositol synthesis by knocking down INO1, which encodes inositol-3-phosphate synthase, the rate-limiting enzyme of inositol synthesis, led to inactivation of GSK-3α by increasing the inhibitory phosphorylation of this kinase. Similarly, the mood-stabilizer VPA effected transient decreases in intracellular inositol, leading to inactivation of GSK-3α. As GSK-3 inhibition has been proposed as a likely therapeutic mechanism of action, the finding that inhibition of inositol synthesis results in inactivation of GSK-3α suggests a unifying hypothesis for mechanism of mood-stabilizing drugs. PMID:25345501

  9. Regulation of inositol phospholipid binding and signaling through syndecan-4

    DEFF Research Database (Denmark)

    Couchman, John R; Vogt, Susan; Lim, Ssang-Taek

    2002-01-01

    inositol phospholipids. In turn, lipid binding stabilizes the syndecan in oligomeric form, with subsequent binding and activation of protein kinase C. The specificity of phospholipid binding and its potential regulation are investigated here. Highest affinity of the syndecan-4 cytoplasmic domain was seen...... examined. Inositol hexakisphosphate, but not inositol tetrakisphosphate, also had high affinity for the syndecan-4 cytoplasmic domain and could compete effectively with PtdIns(4,5)P(2). Since inositol hexaphosphate binding to syndecan-4 does not promote oligomer formation, it is a potential down...

  10. A novel pathway for the synthesis of inositol phospholipids uses cytidine diphosphate (CDP)-inositol as donor of the polar head group.

    Science.gov (United States)

    Jorge, Carla D; Borges, Nuno; Santos, Helena

    2015-07-01

    We describe a novel biosynthetic pathway for glycerophosphoinositides in Rhodothermus marinus in which inositol is activated by cytidine triphosphate (CTP); this is unlike all known pathways that involve activation of the lipid group instead. This work was motivated by the detection in the R. marinus genome of a gene with high similarity to CTP:L-myo-inositol-1-phosphate cytidylyltransferase, the enzyme that synthesizes cytidine diphosphate (CDP)-inositol, a metabolite only known in the synthesis of di-myo-inositol phosphate. However, this solute is absent in R. marinus. The fate of radiolabelled CDP-inositol was investigated in cell extracts to reveal that radioactive inositol was incorporated into the chloroform-soluble fraction. Mass spectrometry showed that the major lipid product has a molecular mass of 810 Da and contains inositol phosphate and alkyl chains attached to glycerol by ether bonds. The occurrence of ether-linked lipids is rare in bacteria and has not been described previously in R. marinus. The relevant synthase was identified by functional expression of the candidate gene in Escherichia coli. The enzyme catalyses the transfer of L-myo-inositol-1-phosphate from CDP-inositol to dialkylether glycerol yielding dialkylether glycerophosphoinositol. Database searching showed homologous proteins in two bacterial classes, Sphingobacteria and Alphaproteobacteria. This is the first report of the involvement of CDP-inositol in phospholipid synthesis. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Inositol transport proteins.

    Science.gov (United States)

    Schneider, Sabine

    2015-04-28

    The cyclic polyol myo-inositol is a key molecule in many different metabolic pathways among all organisms; in addition, it is fundamental for osmotic balance in the mammalian brain. This review sums up inositol transporters from eukaryotic organisms, elucidating their vital role in regulating the intracellular distribution and uptake of inositol. They can be divided into two groups according to their transport mechanisms: (1) sodium ion coupled inositol transporters that belong to the Solute Carrier Families 5 and 6-like Superfamily and, (2) proton coupled inositol symporters that are members of the Major Facilitator Superfamily. Intriguingly members of both families offer promising targets for medical treatment of a variety of diseases. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. Inositol depletion restores vesicle transport in yeast phospholipid flippase mutants.

    Science.gov (United States)

    Yamagami, Kanako; Yamamoto, Takaharu; Sakai, Shota; Mioka, Tetsuo; Sano, Takamitsu; Igarashi, Yasuyuki; Tanaka, Kazuma

    2015-01-01

    In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer. Flippases function in the formation of transport vesicles, but the mechanism remains unknown. Here, we isolate an arrestin-related trafficking adaptor, ART5, as a multicopy suppressor of the growth and endocytic recycling defects of flippase mutants in budding yeast. Consistent with a previous report that Art5p downregulates the inositol transporter Itr1p by endocytosis, we found that flippase mutations were also suppressed by the disruption of ITR1, as well as by depletion of inositol from the culture medium. Interestingly, inositol depletion suppressed the defects in all five flippase mutants. Inositol depletion also partially restored the formation of secretory vesicles in a flippase mutant. Inositol depletion caused changes in lipid composition, including a decrease in phosphatidylinositol and an increase in phosphatidylserine. A reduction in phosphatidylinositol levels caused by partially depleting the phosphatidylinositol synthase Pis1p also suppressed a flippase mutation. These results suggest that inositol depletion changes the lipid composition of the endosomal/TGN membranes, which results in vesicle formation from these membranes in the absence of flippases.

  13. Effects of light on inositol phospholipid metabolism in Dunaliella salina

    International Nuclear Information System (INIS)

    Peeler, T.C.; Thompson, G.A. Jr.

    1989-01-01

    Previous work in our laboratory has shown that inositol phospholipids in Dunaliella salina respond to changes in the osmotic environment. These results and other supporting evidence indicate that an inositol phospholipid signal transduction pathway is functioning in this single-celled alga. We wanted to determine if the metabolism of inositol phospholipids was also affected by changes in the light environment. 32 P orthophosphate was used to label cells under normal growth conditions. Pulse-labeled cells rapidly incorporated 32 P into the inositol phospholipids. PIP and PIP 2 accounted for approx. 20% of the label after a 10 min pulse, although they were only 1.5% of the total phospholipid. When cells were labeled for 10 min in the dark, more than 50% of the 32 P was incorporated into PIP and PIP 2 , showing that rapid PIP and PIP 2 turnover was maintained in the dark, while labeling of other phospholipids was reduced. Photoinhibition had little effect on phospholipid metabolism, even though the rate of O 2 evolution was completely inhibited. The rapid rates of metabolism of inositol phospholipids in D. Salina, even in the dark, further substantiate the hypothesis that inositol phospholipids participate in a signal transduction pathway in this organism

  14. Involvement of inositol in reproduction.

    NARCIS (Netherlands)

    Beemster, P.; Groenen, P.; Steegers-Theunissen, R.P.M.

    2002-01-01

    Inositol is involved in several aspects of reproduction. It affects overall embryogenesis, may prevent neural tube defects, and stimulates the production of lung surfactant. This article will review the involvement of inositol in reproduction. After describing the biologic function of inositol and

  15. The novel synthetic ether lipid inositol-C2-PAF inhibits phosphorylation of the tyrosine kinases Src and FAK independent of integrin activation in transformed skin cells.

    Science.gov (United States)

    Semini, Geo; Hildmann, Annette; Reissig, Hans-Ulrich; Reutter, Werner; Danker, Kerstin

    2011-04-15

    New alkyl-phospholipids that are structurally derived from platelet-activating factor are promising candidates for anticancer treatment. The mechanism of action of derivatives of the platelet-activating factor is distinctly different from that of known DNA- or tubulin-targeting anticancer agents because they are incorporated into cell membranes, where they accumulate and interfere with a wide variety of key enzymes. We recently presented evidence of a novel group of alkyl-phospholipids, glycosidated phospholipids that efficiently inhibit cell proliferation. One member of this group, inositol-C2-PAF (Ino-C2-PAF), displays high efficacy and low cytotoxicity in HaCaT-cells, an immortalized non-tumorigenic skin keratinocyte cell line. Here, we show that Ino-C2-PAF also inhibits the motility of the skin-derived transformed cell lines HaCaT and squamous cell carcinoma (SCC)-25. This decrease in motility is accompanied by an altered F-actin cytoskeleton, increased clustering of integrins, and increased cell-matrix adhesion. Despite enhanced integrin clustering and matrix adhesion, we observed less phosphorylation of the cytoplasmic tyrosine kinases focal adhesion kinase (FAK) and Src, key regulators of cellular motility, at focal adhesion sites. Transient transfection of constitutively active variants of FAK and Src could at least in part bybass this inhibitory effect of Ino-C2-PAF. This fact indicates that Ino-C2-PAF interferes with the fine-tuned balance between adhesion and migration. Ino-C2-PAF at least partially uncouples integrin-mediated attachment from subsequent integrin-dependent signaling steps, which inhibits migration in transformed keratinocyte cell lines. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Source of 3H-labeled inositol bis- and monophosphates in agonist-activated rat parotid acinar cells

    International Nuclear Information System (INIS)

    Hughes, A.R.; Putney, J.W. Jr.

    1989-01-01

    The kinetics of [3H]inositol phosphate metabolism in agonist-activated rat parotid acinar cells were characterized in order to determine the sources of [3H]inositol monophosphates and [3H]inositol bisphosphates. The turnover rates of D-myo-inositol 1,4,5-trisphosphate and its metabolites, D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,3,4-trisphosphate, were examined following the addition of the muscarinic receptor antagonist, atropine, to cholinergically stimulated parotid cells. D-myo-Inositol 1,4,5-trisphosphate declined with a t1/2 of 7.6 +/- 0.7 s, D-myo-inositol 1,3,4-trisphosphate declined with a t1/2 of 8.6 +/- 1.2 min, and D-myo-inositol 1,4-bisphosphate was metabolized with a t1/2 of 6.0 +/- 0.7 min. The sum of the rates of flux through D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,3,4-trisphosphate (2.54% phosphatidylinositol/min) did not exceed the calculated rate of breakdown of D-myo-inositol 1,4,5-trisphosphate (2.76% phosphatidylinositol/min). Thus, there is no evidence for the direct hydrolysis of phosphatidylinositol 4-phosphate in intact cells since D-myo-inositol 1,4-bisphosphate formation can be attributed to the dephosphorylation of D-myo-inositol 1,4,5-trisphosphate. The source of the [3H]inositol monophosphates also was examined in cholinergically stimulated parotid cells. When parotid cells were stimulated with methacholine, D-myo-inositol 1,4,5-trisphosphate, D-myo-inositol 1,3,4,5-tetrakisphosphate, D-myo-inositol 1,4-bisphosphate, and D-myo-inositol 4-monophosphate levels increased within 2 s, whereas D-myo-inositol 1-monophosphate accumulation was delayed by several seconds. Rates of [3H]inositol monophosphate accumulation also were examined by the addition of LiCl to cells stimulated to steady state levels of [3H]inositol phosphates

  17. Phytic acid and myo-inositol support adipocyte differentiation and improve insulin sensitivity in 3T3-L1 cells.

    Science.gov (United States)

    Kim, Jin Nam; Han, Sung Nim; Kim, Hye-Kyeong

    2014-08-01

    Phytic acid, also known as myo-inositol hexaphosphate, has been shown to lower blood glucose levels and to improve insulin sensitivity in rodents. We investigated the effects of phytic acid and myo-inositol on differentiation, insulin-stimulated glucose uptake, and lipolysis of adipocytes to test the hypothesis that the antidiabetic properties of phytic acid and myo-inositol are mediated directly through adipocytes. 3T3-L1 cells were treated with 10, 50, or 200 μmol/L of phytic acid or myo-inositol. Oil Red O staining and an intracellular triacylglycerol assay were used to determine lipid accumulation during adipocyte differentiation. Immunoblotting and real-time polymerase chain reaction (PCR) were performed to evaluate expression of transcription factors, a target protein, and insulin signaling molecules. Phytic acid and myo-inositol exposures increased lipid accumulation in a dose-dependent manner (P inositol (P inositol treatments (P inositol treatments. In fully differentiated adipocytes, phytic acid and myo-inositol reduced basal lipolysis dose dependently (P inositol increase insulin sensitivity in adipocytes by increasing lipid storage capacity, improving glucose uptake, and inhibiting lipolysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The response to inositol: regulation of glycerolipid metabolism and stress response signaling in yeast

    Science.gov (United States)

    Henry, Susan A.; Gaspar, Maria L.; Jesch, Stephen A.

    2014-01-01

    This article focuses on discoveries of the mechanisms governing the regulation of glycerolipid metabolism and stress response signaling in response to the phospholipid precursor, inositol. The regulation of glycerolipid lipid metabolism in yeast in response to inositol is highly complex, but increasingly well understood, and the roles of individual lipids in stress response are also increasingly well characterized. Discoveries that have emerged over several decades of genetic, molecular and biochemical analyses of metabolic, regulatory and signaling responses of yeast cells, both mutant and wild type, to the availability of the phospholipid precursor, inositol are discussed. PMID:24418527

  19. Inositol metabolism in WRK-1 cells. Relationship of hormone-sensitive to -insensitive pools of phosphoinositides

    International Nuclear Information System (INIS)

    Monaco, M.E.

    1987-01-01

    Previous studies have indicated the existence of two separate pools of phosphoinositides in WRK-1 cells; one is labile and hormone-sensitive with respect to turnover, while the other is stable. Hormonal stimulation results in a rapid increase in 32 Pi incorporation into the sensitive pool, while in the absence of hormone, incorporation of 32 Pi into this pool is slow. Results are quite different when [ 3 H]inositol is the precursor utilized. Incorporation of [ 3 H]inositol into hormone-sensitive phosphoinositides is not stimulated in the presence of hormone, suggesting entry of this exogenous precursor into the cycle by a route other than the resynthetic phase of the cycle. Furthermore, failure of hormone to induce loss of [ 3 H]phosphoinositide in pulse-chase experiments in the absence of lithium suggests reutilization of the [ 3 H]inositol moiety generated by phosphodiesteratic cleavage of hormone-sensitive phosphoinositide. Time course studies indicate that the relative rates of incorporation of [ 3 H]inositol into sensitive and insensitive phosphoinositide remain constant from 2 to 24 h. Several factors are capable of increasing [ 3 H]inositol incorporation into hormone-insensitive phosphoinositide including vasopressin, calcium ionophores, and manganese. On the other hand, vasopressin treatment appears to decrease incorporation of [ 3 H]inositol into the hormone-sensitive pool, probably by shifting the equilibrium between phosphoinositides and inositol phosphates, since the decrease in radioactivity observed in the phosphoinositides is equaled by the increase observed in that in the inositol phosphates

  20. Two inositol hexakisphosphate kinases drive inositol pyrophosphate synthesis in plants

    Science.gov (United States)

    Inositol pyrophosphates are novel cellular signaling molecules with newly discovered roles in energy sensing and metabolic control. Studies in eukaryotes have revealed that these compounds turn over rapidly, and thus only small amounts accumulate. Inositol pyrophosphates have not been the subject of...

  1. Inositol-phosphodihydroceramides in the periodontal pathogen Tannerella forsythia: Structural analysis and incorporation of exogenous myo-inositol.

    Science.gov (United States)

    Megson, Zoë Anne; Pittenauer, Ernst; Duda, Katarzyna Anna; Engel, Regina; Ortmayr, Karin; Koellensperger, Gunda; Mach, Lukas; Allmaier, Günter; Holst, Otto; Messner, Paul; Schäffer, Christina

    2015-11-01

    Unique phosphodihydroceramides containing phosphoethanolamine and glycerol have been previously described in Porphyromonas gingivalis. Importantly, they were shown to possess pro-inflammatory properties. Other common human bacteria were screened for the presence of these lipids, and they were found, amongst others, in the oral pathogen Tannerella forsythia. To date, no detailed study into the lipids of this organism has been performed. Lipids were extracted, separated and purified by HPTLC, and analyzed using GC-MS, ESI-MS and NMR. Of special interest was how T. forsythia acquires the metabolic precursors for the lipids studied here. This was assayed by radioactive and stable isotope incorporation using carbon-14 and deuterium labeled myo-inositol, added to the growth medium. T. forsythia synthesizes two phosphodihydroceramides (Tf GL1, Tf GL2) which are constituted by phospho-myo-inositol linked to either a 17-, 18-, or 19-carbon sphinganine, N-linked to either a branched 17:0(3-OH) or a linear 16:0(3-OH) fatty acid which, in Tf GL2, is, in turn, ester-substituted with a branched 15:0 fatty acid. T. forsythia lacks the enzymatic machinery required for myo-inositol synthesis but was found to internalize inositol from the medium for the synthesis of both Tf GL1 and Tf GL2. The study describes two novel glycolipids in T. forsythia which could be essential in this organism. Their synthesis could be reliant on an external source of myo-inositol. The effects of these unique lipids on the immune system and their role in bacterial virulence could be relevant in the search for new drug targets. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Lack of 13C-label incorporation suggests low turnover rates of thaumarchaeal intact polar tetraether lipids in sediments from the Iceland shelf

    Science.gov (United States)

    Lengger, S. K.; Lipsewers, Y. A.; de Haas, H.; Sinninghe Damsté, J. S.; Schouten, S.

    2014-01-01

    Thaumarchaeota are amongst the most abundant microorganisms in aquatic environments, however, their metabolism in marine sediments is still debated. Labeling studies in marine sediments have previously been undertaken, but focused on complex organic carbon substrates which Thaumarchaeota have not yet been shown to take up. In this study, we investigated the activity of Thaumarchaeota in sediments by supplying different 13C-labeled substrates which have previously been shown to be incorporated into archaeal cells in water incubations and/or enrichment cultures. We determined the incorporation of 13C-label from bicarbonate, pyruvate, glucose and amino acids into thaumarchaeal intact polar lipid-glycerol dibiphytanyl glycerol tetraethers (IPL-GDGTs) during 4-6 day incubations of marine sediment cores from three sites on the Iceland shelf. Thaumarchaeal intact polar lipids, in particular crenarchaeol, were detected at all stations and concentrations remained constant or decreased slightly upon incubation. No 13C incorporation in any IPL-GDGT was observed at stations 2 (clay-rich sediment) and 3 (organic-rich sediment). In bacterial/eukaryotic IPL-derived fatty acids at station 3, contrastingly, a large uptake of 13C label (up to + 80‰ ) was found. 13C was also respired during the experiment as shown by a substantial increase in the 13C content of the dissolved inorganic carbon. In IPL-GDGTs recovered from the sandy sediments at station 1, however, some enrichment in δ13C (1-4‰ ) was detected after incubation with bicarbonate and pyruvate. The low incorporation rates suggest a low activity of Thaumarchaeota in marine sediments and/or a low turnover rate of thaumarchaeal IPL-GDGTs due to their low degradation rates. Cell numbers and activity of sedimentary Thaumarchaeota based on IPL-GDGT measurements may thus have previously been overestimated.

  3. New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer.

    Science.gov (United States)

    Erneux, Christophe; Ghosh, Somadri; Ramos, Ana Raquel; Edimo, William's Elong

    2016-01-01

    Inositol polyphosphate 5-phosphatases act on inositol phosphates and phosphoinositides as substrates. They are 10 different isoenzymes and several splice variants in the human genome that are involved in a series of human pathologies such as the Lowe syndrome, the Joubert and MORM syndromes, breast cancer, glioblastoma, gastric cancer and several other type of cancers. Inositol 5-phosphatases can be amplified in human cancer cells, whereas the 3- and 4- phosphatase tumor suppressor PTEN and INPP4B, repectively are often repressed or deleted. The inositol 5-phosphatases are critically involved in a complex network of higly regulated phosphoinositides, affecting the lipid content of PI(3, 4, 5)P3, PI(4, 5)P2 and PI(3, 4)P2. This has an impact on the normal behavior of many intracellular target proteins e.g. protein kinase B (PKB/Akt) or actin binding proteins and final biological responses. The production of PI(3, 4P)2 by dephosphorylation of the substrate PI(3, 4, 5)P3 is particularly important as it produces a new signal messenger in the control of cell migration, invasion and endocytosis. New inhibitors/activators of inositol 5- phosphatases have recently been identified for the possible control of their activity in several human pathologies such as inflamation and cancer.

  4. Membrane depolarization and carbamoylcholine stimulate phosphatidylinositol turnover in intact nerve terminals

    International Nuclear Information System (INIS)

    Audigier, S.M.P.; Wang, J.K.T.; Greengard, P.

    1988-01-01

    Synaptosomes, purified from rat cerebral cortex, were prelabeled with [ 3 H]inositol to study phosphatidylinositol turnover in nerve terminals. Labeled synaptosomes were either depolarized with 40 mM K + or exposed to carbamoylcholine (carbachol). K + depolarization increased the level of inositol phosphates in a time-dependent manner. The inositol bisphosphate level also increased rapidly, but its elevated level was sustained during continued depolarization. The elevated level of inositol bisphosphate was reversed upon repolarization of the synaptosomes. The level of inositol monophosphate increased slowly to 120-130% of control. These effects of K + depolarization depended on the presence of Ca 2+ in the incubation medium. Carbachol stimulated the turnover of phosphatidylinositol in a dose- and time-dependent manner. The level of inositol bisphosphate increased to 210% of control, and this maximal response was seen from 15 to 60 min. Accumulation of inositol monophosphate was larger than that of inositol bisphosphate, but its time course was slower. Atropine and pirenzepine inhibited the carbachol effect with high affinities. These data show that both Ca 2+ influx and M 1 muscarinic receptor activation stimulate phospholipase C activity in synaptosomes, suggesting that phosphatidylinositol turnover may be involved in regulating neurotransmitter release from nerve terminals

  5. Inositol uptake in rat aorta

    International Nuclear Information System (INIS)

    Rapoport, R.M.; Van Gorp, C.; Chang, Ki-Churl

    1990-01-01

    3 H-inositol uptake into deendothelialized aorta was linear for at least 2 h and was composed of both a saturable, Na + -dependent, and a nonsaturable, Na + -independent component. The Na + -dependent component of inositol uptake had a K m of 50 μM and a V max of 289 pmol/mg prot/h. Exposure to LiCl, ouabain, or Ca 2+ - free Krebs-Ringer bicarbonate solution inhibited uptake. Metabolic poisoning with dinitrophenol, as well as incubation with phloretin, an inhibitor of carrier-mediated hexose transport, also inhibited uptake. Exposure to norepinephrine decreased inositol uptake, while phorbol myristate acetate was without effect. Isobutylmethylxanthine significantly increased inositol uptake, while the increased uptake due to dibutyryl cyclic AMP and forskolin were not statistically significant. Sodium nitroprusside, and activator of guanylate cyclase, and 8-bromo cyclic GMP, were without effect on uptake, as was methylene blue, an inhibitor of guanylate cyclase. Inositol uptake into the aorta was increased when the endothelium was allowed to remain intact, although this effect was likely due to uptake in both the endothelial and smooth muscle cells

  6. Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells

    International Nuclear Information System (INIS)

    Sesko, A.; Mossman, B.; Cabot, M.

    1990-01-01

    Metabolism of inositol phospholipids and phosphatidylcholine was investigated in tracheobronchial epithelial cells exposed to mitogenic concentrations of crocidolite asbestos. Alterations in levels of diacylglycerol, the endogenous activator of protein kinase C, and inositol polyphosphates, presumed mobilizers of intracellular calcium, were examined. Cultures labeled with [ 3 H]diacylglycerol. In contrast, crocidolite-exposed cells labeled with [ 3 H]myristic acid or [ 3 H]choline did not display elevated production of [ 3 H]diacylglycerol or release of [ 3 H]choline metabolites (i.e., evidence of phosphatidylcholine hydrolysis). The soluble tumor promoter phorbol 12-myristate 13-acetate catalyzed both of these changes. myo-[ 3 H]Inositol-labeled cells exposed as briefly as 10 min to mitogenic concentrations of crocidolite demonstrated elevations in [ 3 H]inositol mono-, tris-, and terakisphosphates, phenomena indicating turnover of inositol phospholipids. The detection of diacylglycerol and inositol phosphates in crocidolite asbestos-exposed cells suggests that this fibrous tumor promoter activates phospholipase C as it stimulates cellular proliferation

  7. 21 CFR 184.1370 - Inositol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Inositol. 184.1370 Section 184.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1370 Inositol. (a) Inositol, or myo-inositol (C6H12O6, CAS Reg. No. 87-89-8...

  8. 21 CFR 582.5370 - Inositol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Inositol. 582.5370 Section 582.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... § 582.5370 Inositol. (a) Product. Inositol. (b) Conditions of use. This substance is generally...

  9. Inositol Hexakisphosphate Kinase 1 (IP6K1) Regulates Inositol Synthesis in Mammalian Cells*♦

    Science.gov (United States)

    Yu, Wenxi; Ye, Cunqi; Greenberg, Miriam L.

    2016-01-01

    myo-Inositol, the precursor of all inositol compounds, has pivotal roles in cell metabolism and signaling pathways. Although physiological studies indicate a strong correlation between abnormal intracellular inositol levels and neurological disorders, very little is known about the regulation of inositol synthesis in mammalian cells. In this study, we report that IP6K1, an inositol hexakisphosphate kinase that catalyzes the synthesis of inositol pyrophosphate, regulates inositol synthesis in mammalian cells. Ip6k1 ablation led to profound changes in DNA methylation and expression of Isyna1 (designated mIno1), which encodes the rate-limiting enzyme inositol-3-phosphate synthase. Interestingly, IP6K1 preferentially bound to the phospholipid phosphatidic acid, and this binding was required for IP6K1 nuclear localization and the regulation of mIno1 transcription. This is the first demonstration of IP6K1 as a novel negative regulator of inositol synthesis in mammalian cells. PMID:26953345

  10. Inositol-Limited Growth, Repair, and Translocation in an Inositol-Requiring Mutant of Neurospora crassa

    OpenAIRE

    Hanson, Barbara A.

    1980-01-01

    The biochemical consequences of inositol limitation in an inositol auxotroph of Neurospora crassa have been examined as a means of disclosing the cellular role of inositol. The cellular levels of inositol in the inl mutant were proportional to the concentration of inositol in the growth medium whereas inositol phosphate levels remained relatively constant at about 0.1 μmol/g (dry weight). After 72 h of growth, about 57-fold more protein per milligram (dry weight) was released by the mutant gr...

  11. A Mnemonic for the Inositols

    Science.gov (United States)

    Painter, Terence J.

    1996-10-01

    The mnemonic derives from the mythical tale of Scylla and Charybdis in Homer's Odyssey (chapter 12). It takes the form of an imaginary headline in a newspaper: SCYLLA MEETS CHARYBDIS - EPIC NEWS MUCH ALARMS SICILY. The first two or three letters in each of these eight words remind the user that the nine configurational prefixes are scyllo-, meso-, (or myo-), chiro- [(+) and (-)], epi-, neo-, muco-, allo-, and cis-, respectively. The mnemonic also arranges the prefixes in an order that allows the configurations to be derived in a logical manner by performing a defined sequence of imaginary configurational inversions (epimerizations) around a cyclohexane ring. The all-equatorial, chair conformation of scyllo-inositol is selected as the starting point, and the sequence of inversions is defined by a systematic permutation of possibilities for performing one, two or three inversions in succession (1; 1 and 2; 1 and 3; 1 and 4; 1, 2 and 3; 1, 2 and 4; and finally 1, 3 and 5). In the case of the two chiro-inositols, the enantiomeric form is determined simply by the direction (clockwise or counterclockwise) around the ring in which the imaginary inversions are performed. This also applies formally to allo-inositol, but in that case the two optical enantiomers are isoenergetic chair conformers in rapid equilibrium.

  12. Abnormalities in myo-inositol metabolism associated with type 2 diabetes in mice fed a high-fat diet: benefits of a dietary myo-inositol supplementation.

    Science.gov (United States)

    Croze, Marine L; Géloën, Alain; Soulage, Christophe O

    2015-06-28

    We previously reported that a chronic supplementation with myo-inositol (MI) improved insulin sensitivity and reduced fat accretion in mice. We then tested the potency of such dietary intervention in the prevention of insulin resistance in C57BL/6 male mouse fed a high-fat diet (HFD). In addition, some abnormalities in inositol metabolism were reported to be associated with insulin resistance in several animal and human studies. We then investigated the presence of such anomalies (i.e. inosituria and an inositol intra-tissue depletion) in this diet-induced obesity (DIO) mouse model, as well as the potential benefit of a MI supplementation for inositol intra-tissue deficiency correction. HFD (60 % energy from fat) feeding was associated with inosituria and inositol intra-tissue depletion in the liver and kidneys. MI supplementation (0·58 mg/g per d) restored inositol pools in kidneys (partially) and liver (fully). HFD feeding for 4 months induced ectopic lipid redistribution to liver and muscles, fasting hyperglycaemia and hyperinsulinaemia, insulin resistance and obesity that were not prevented by MI supplementation, despite a significant improvement in insulin sensitivity parameter K insulin tolerance test and a reduction in white adipose tissue (WAT) mass ( - 17 %, Pinositol metabolism in association with a diabetic phenotype (i.e. insulin resistance and fasting hyperglycaemia) in a DIO mouse model. Dietary MI supplementation was efficient in the prevention of inositol intra-tissue depletion, but did not prevent insulin resistance or obesity efficiently in this mouse model.

  13. Osmotic stress-induced phosphoinositide and inositol phosphate signalling in plants

    NARCIS (Netherlands)

    Munnik, T.; Vermeer, J.E.M.

    2010-01-01

    Polyphosphoinositides (PPIs) became famous for their role in inositol-1,4,5-trisphosphate (InsP3) mediated-Ca2+ signalling in mammalian cells, generated through signal-activated phospholipase C (PLC) hydrolysis of the minor membrane lipid, phosphatidylinositol-4,5-bisphosphate. For many years, the

  14. Effects of combined inositol hexakisphosphate and inositol supplement on antioxidant activity and metabolic enzymes in the liver of streptozotocin-induced type 2 diabetic rats.

    Science.gov (United States)

    Foster, Shadae R; Dilworth, Lowell L; Thompson, Rory K; Alexander-Lindo, Ruby L; Omoruyi, Felix O

    2017-09-25

    Diabetes mellitus is associated with elevated reactive oxygen species, lipid abnormalities, reduced antioxidant activity and organ damage. This study examines the effects of combined inositol hexakisphosphate (IP6) and inositol supplement on antioxidant levels and other biochemical parameters in the liver of type 2 diabetic rats. Five groups of Sprague-Dawley rats were studied. Six rats were fed normal diet (non-diabetic control), while 24 rats were fed high-fat diet (HFD) for 4 weeks. Diabetes was induced in 18 of the rats fed HFD by intraperitoneal administration of streptozotocin. The diabetic rats were separated into three groups namely: combined IP6 and inositol, glibenclamide and diabetic control. The non-diabetic group fed high-fat diet was classified as a high-fat control group. For the final four weeks of the experiment, all rats were fed normal diet and given their respective treatment regimes. Hepatic antioxidant status, metabolic enzyme activity, lipid profile, peroxidative damage and liver histology, as well as, serum aminotransferase and alkaline phosphatase activities, and total bilirubin concentration were assessed. Treatment with combined IP6 and inositol supplement significantly increased liver reduced glutathione and high-density lipoprotein levels while liver triglyceride levels and serum alkaline phosphatase activity were significantly reduced by 27%, 50%, 38.5%, and 69.2% respectively compared to the diabetic control. Hepatic superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase activities were significantly upregulated by 55%, 26% and 53% respectively in the diabetic rats treated with combined IP6 and inositol compared to the diabetic control. Combined IP6 and inositol treatment resulted in the preservation of liver cell integrity and improved antioxidant status in type 2 diabetic rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Phosphoinositide turnover in cell growth and transformation

    International Nuclear Information System (INIS)

    Fleischman, L.F.

    1987-01-01

    Interaction of cells with various stimuli triggers a common signal transduction pathway involving breakdown and resynthesis of the minor membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP 2 ). Hydrolysis of PIP 2 by phospholipase C generates two key catabolites-inositol-1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DAG)-which mediate and amplify cellular responses. These studies provide evidence for potential involvement of this pathway in oncogenic transformation and cell cycle progression. Altered levels of PIP 2 and its breakdown products were found in cells transformed by ras oncogenes, in contrast to untransformed counterparts. Steady-state levels of PIP 2 , DAG and inositol phosphates were measured in NIH 3T3 and NRK cells metabolically labelled with 3 H-glycerol and 3 H-inositol. DAG and inositol phosphate levels were significantly elevated by 2.5-3 fold in the transformed cells while levels of PIP 2 were decreased. These findings suggest that the ras protein may activate phospholipase C. Elevated DAG content in the transformed cells was also measured by phosphorylation of DAG using a partially purified DAG kinase, indicating that the differences seen could not be attributed to differences in labelling between the cell lines

  16. 3H-labelling of myo-inositol at L-C1 minimizes aberrant 3H in nucleotides

    DEFF Research Database (Denmark)

    Christensen, Søren; Jensen, Annelie Kolbjørn; Simonsen, L.O.

    2002-01-01

    aberrant K3H-labelling, inositol phosphate signalling, (3H)myo-inositol labelling, myo-inositol metabolism......aberrant K3H-labelling, inositol phosphate signalling, (3H)myo-inositol labelling, myo-inositol metabolism...

  17. Inositol as putative integrative treatment for PCOS.

    Science.gov (United States)

    Genazzani, Alessandro D

    2016-12-01

    Studies over the last decade have demonstrated that some polycystic ovary syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently from being overweight or obese. This induces the risk of developing type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments. As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols. Such compounds are mainly represented in humans by two inositol stereoisomers: myo-inositol (MYO) and d-chiro-inositol (DCI). MYO is the precursor of inositol triphosphate, a second messenger that regulates thyroid-stimulating hormone (TSH) and FSH as well as insulin. DCI derives from the conversion of myo-inositol via an insulin-dependent pathway. Several preliminary studies have indicated possible benefits of inositol therapy in PCOS patients, but to date no meta-analysis has been performed. This review aims to give clinical insights for the clinical use of inositol in PCOS. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

    Directory of Open Access Journals (Sweden)

    Antonio Simone Laganà

    2016-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI and D-chiro-inositol (DCI, the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

  19. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

    Science.gov (United States)

    Rossetti, Paola; Buscema, Massimo; Condorelli, Rosita Angela; Gullo, Giuseppe; Triolo, Onofrio

    2016-01-01

    Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS. PMID:27579037

  20. Activity of Escherichia coli, Aspergillus niger, and Rye Phytase toward Partially Phosphorylated myo-Inositol Phosphates.

    Science.gov (United States)

    Greiner, Ralf

    2017-11-08

    Kinetic parameters for the dephosphorylation of sodium phytate and a series of partially phosphorylated myo-inositol phosphates were determined at pH 3.0 and pH 5.0 for three phytase preparations (Aspergillus niger, Escherichia coli, rye). The enzymes showed lower affinity and turnover numbers at pH 3 compared to pH 5 toward all myo-inositol phosphates included in the study. The number and distribution of phosphate groups on the myo-inositol ring affected the kinetic parameters. Representatives of the individual phytate dephosphorylation pathways were identified as the best substrates of the phytases. Within the individual phytate dephosphorylation pathways, the pentakisphosphates were better substrates compared to the tetrakisphosphates or phytate itself. E. coli and rye phytase showed comparable activities at both pH values toward the tetrakis- and trisphosphate, whereas A. niger phytase exhibited a higher activity toward the tetrakisphosphate. A myo-inositol phosphate with alternate phosphate groups was shown to be not significantly dephosphorylated by the phytases.

  1. Turnover among healthcare professionals.

    Science.gov (United States)

    Wood, Ben D

    2009-01-01

    Turnover among healthcare professionals is a costly consequence. The existing body of knowledge on healthcare professional turnover is correlated with job satisfaction levels. A landmark study differentiated 2 areas of job satisfaction categories: satisfiers and dissatisfiers (intrinsic and extrinsic motivators). The aim of this article is to examine existing research on precursors of turnover, such as burnout behaviors experienced by healthcare professionals, job satisfaction levels, employee organizational commitment, health complications which precede turnover, some current strategies to reduce turnover, and some effects CEO turnover has on employee turnover intentions.

  2. Effect of atropine and gammahydroxybutyrate on ischemically induced changes in the level of radioactivity in [3H]inositol phosphates in gerbil brain in vivo

    International Nuclear Information System (INIS)

    Wikiel, H.; Halat, G.; Strosznajder, J.

    1988-01-01

    Brain ischemia in gerbils was induced by ligation of both common carotid arteries for 1 min or 10 min. Sham-operated animals served as controls. Intracerebral injection of [3H]inositol into gerbil brain 16 hr before ischemic insult resulted in equilibration of the label between inositol lipids and water-soluble inositol phosphate. A short ischemic period (1 min) resulted in a statistically significant increase in the radioactivity of inositol triphosphate (IP3) and inositol monophosphate (IP), by about 48% and 79%, respectively, with little change in that of the intermediate inositol biphosphate (IP2), which increased by about 16%. When the ischemic period was prolonged (10 min), an increase in the radioactivity of inositol monophosphate exclusively, by about 84%, was observed. The level of radioactivity in inositol phosphates IP2 and IP3 decreased by about 50%, probably as a consequence of phosphatase activation by the ischemic insult. The agonist of the cholinergic receptor, carbachol, injected intracerebrally (40 micrograms per animal) increased accumulation of radioactivity in all inositol phosphates. The level of radioactivity in IP3, IP2, and IP was elevated by about 40, 23, and 147%, respectively. The muscarinic cholinergic antagonist, atropine, injected intraperitoneally in doses of 100 mg/kg body wt. depressed phosphoinositide metabolism in control animals. The level of radioactivity in water-soluble inositol metabolites in the brain of animals pretreated with atropine was evidently about 32% lower than in untreated animals. Pretreatment with atropine decreased the radioactivity of all inositol phosphates in the brain of animals subjected to 1-min ischemia and the radioactivity of IP in the case of 10-min brain ischemia

  3. Inositol Hexakisphosphate Kinase 1 (IP6K1) Regulates Inositol Synthesis in Mammalian Cells.

    Science.gov (United States)

    Yu, Wenxi; Ye, Cunqi; Greenberg, Miriam L

    2016-05-13

    myo-Inositol, the precursor of all inositol compounds, has pivotal roles in cell metabolism and signaling pathways. Although physiological studies indicate a strong correlation between abnormal intracellular inositol levels and neurological disorders, very little is known about the regulation of inositol synthesis in mammalian cells. In this study, we report that IP6K1, an inositol hexakisphosphate kinase that catalyzes the synthesis of inositol pyrophosphate, regulates inositol synthesis in mammalian cells. Ip6k1 ablation led to profound changes in DNA methylation and expression of Isyna1 (designated mIno1), which encodes the rate-limiting enzyme inositol-3-phosphate synthase. Interestingly, IP6K1 preferentially bound to the phospholipid phosphatidic acid, and this binding was required for IP6K1 nuclear localization and the regulation of mIno1 transcription. This is the first demonstration of IP6K1 as a novel negative regulator of inositol synthesis in mammalian cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels.

    Science.gov (United States)

    Dai, Gucan; Yu, Haijie; Kruse, Martin; Traynor-Kaplan, Alexis; Hille, Bertil

    2016-06-07

    Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na(+)/myo-inositol cotransporter (SMIT1) and myo-inositol supplementation enlarged intracellular PI(4,5)P2 pools, modulated several PI(4,5)P2-dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycin-recruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myo-inositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several "physiological" manipulations that alter the PI(4,5)P2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells.

  5. An analysis of myo-[3H]inositol trisphosphates found in myo-[3H]inositol prelabelled avian erythrocytes.

    OpenAIRE

    Stephens, L R; Hawkins, P T; Downes, C P

    1989-01-01

    Evidence is presented to show that acid extracts of avian erythrocytes prelabelled for 24-48 h with myo-[3H]inositol contain the following myo-[3H]inositol trisphosphates (expressed as a percentage of total myo-[3H]inositol trisphosphates extracted): 36% myo-[3H]inositol 1,4,5-trisphosphate; 33.7% myo-[3H]inositol 1,3,4-trisphosphate; 13% myo-[3H]inositol 3,4,5-trisphosphate; 9.7% myo-[3H]inositol 3,4,6-trisphosphate; 4.4% myo-[3H]inositol 1,4,6-trisphosphate and 3.3% myo-[3H]inositol 1,3,6-t...

  6. Pathway for inositol 1,3,4-trisphosphate and 1,4-bisphosphate metabolism.

    OpenAIRE

    Inhorn, R C; Bansal, V S; Majerus, P W

    1987-01-01

    We prepared [3H]inositol-,3-[32P]phosphate-and 4-[32P]phosphate-labeled inositol phosphate substrates to investigate the metabolism of inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate. In crude extracts of calf brain, inositol 1,3,4-trisphosphate is first converted to inositol 3,4-bisphosphate, then the inositol 3,4-bisphosphate intermediate is further converted to inositol 3-phosphate. Similarly, inositol 1,4-bisphosphate is converted to inositol 4-phosphate, and no inositol 1-phos...

  7. Finding the best therapeutic approach for PCOS: the importance of inositol(s) bioavailability.

    Science.gov (United States)

    Orrù, B; Circo, R; Logoteta, P; Petousis, S; Carlomagno, G

    2017-06-01

    Broadening clinical evidence has markedly designated inositol(s) as a common and effective therapeutic approach for PCOS and infertility. Although considerable research has been focused on the use in clinical practice of myo-inositol (myo-ins) and D-chiro-inositol (D-chiro-ins), the two major inositol stereoisomers, less attention has been paid to their bioavailability. Therefore, the aim of this paper is to gather and analyze information on inositol(s) bioavailability, to better delineate its optimal concentration for scientific and clinical purposes. Throughout the search in PubMed, Google Scholar, and ResearchGate we identified only two studies that investigated the pharmacokinetic (PK) profile of different myo-ins administrations. This analysis found no advantage in terms of PK for single 4 g dosing of myo-ins compared to 2 g twice a day, which allowed to get a 24-hour coverage, contrary to the singular dose. Indeed, the differences regarding the area under the curve (AUC) between the two PK profiles are linked only to the maximum concentration (Cmax) but not to the time variable. In conclusion, splitting the therapeutic dosage of 4 g myo-ins in two distinct administrations seems to be the best approach for a full-day coverage.

  8. Myo-inositol vs. D-chiro inositol in PCOS treatment.

    Science.gov (United States)

    Formuso, C; Stracquadanio, M; Ciotta, L

    2015-08-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women in fertile age. It is an endocrine and metabolic disorder characterized by oligo-anovulation, hyperandrogenism and insulin-resistance. Various therapeutic approaches have been attempted in PCOS, including diet and the use of pharmacological agents such as oral contraceptives (OCs) or anti-androgens. Recently, the introduction of inositol in the treatment plan has proved to be as reasonable as useful in countering the endocrine-metabolic disorders of this syndrome. The aim of our study was to compare the clinical, endocrine and metabolic response after 6 months of therapy in 137 PCOS women characterized by oligomenorrhea and/or acne and/or mild hirsutism and insulin-resistance. The patients were treated with myo-inositol or with D-chiro-inositol or with placebo. Our study showed that both myo-inositol (MI-PG) and D-chiro inositol (DCI-PG) treatments are able to significantly improve the regularity of the menstrual cycle, the Acne Score, the endocrine and metabolic parameters and the insulin-resistence in young, overweight, PCOS patients. Definitely, we assumed that both treatments with myo-inositol and with D-chiro inositol could be proposed as a potential valid therapeutic approach for the treatment of patients with PCOS. Additionally, further examination and for a longer period of treatment are needed.

  9. Biochemistry and genetics of inositol phosphate metabolism in Dictyostelium

    NARCIS (Netherlands)

    Van Haastert, PJM; Van Dijken, P.; Thiery, JP

    1999-01-01

    Biochemical and genetic data on the metabolism of inositol phosphates in the micro-organism Dictyostelium are combined in a scheme composed of in five subroutes. The first subroute is the inositol cycle as found in other organisms: inositol is incorporated into phospholipids that are hydrolysed by

  10. Biochemistry and genetics of inositol phosphate metabolism in Dictyostelium

    NARCIS (Netherlands)

    vanHaastert, PJM; van Dijken, P.

    1997-01-01

    Biochemical and genetic data on the metabolism of inositol phosphates in the microorganism Dictyostelium are combined in a scheme composed of in five subroutes. The first subroute is the inositol cycle as found in other organisms:inositol is incorporated into phospholipids that are hydrolysed by PLC

  11. myo-Inositol Uptake Is Essential for Bulk Inositol Phospholipid but Not Glycosylphosphatidylinositol Synthesis in Trypanosoma brucei*

    Science.gov (United States)

    Gonzalez-Salgado, Amaia; Steinmann, Michael E.; Greganova, Eva; Rauch, Monika; Mäser, Pascal; Sigel, Erwin; Bütikofer, Peter

    2012-01-01

    myo-Inositol is an essential precursor for the production of inositol phosphates and inositol phospholipids in all eukaryotes. Intracellular myo-inositol is generated by de novo synthesis from glucose 6-phosphate or is provided from the environment via myo-inositol symporters. We show that in Trypanosoma brucei, the causative pathogen of human African sleeping sickness and nagana in domestic animals, myo-inositol is taken up via a specific proton-coupled electrogenic symport and that this transport is essential for parasite survival in culture. Down-regulation of the myo-inositol transporter using RNA interference inhibited uptake of myo-inositol and blocked the synthesis of the myo-inositol-containing phospholipids, phosphatidylinositol and inositol phosphorylceramide; in contrast, it had no effect on glycosylphosphatidylinositol production. This together with the unexpected localization of the myo-inositol transporter in both the plasma membrane and the Golgi demonstrate that metabolism of endogenous and exogenous myo-inositol in T. brucei is strictly segregated. PMID:22351763

  12. Myo-Inositol content determined by myo-inositol biosynthesis and oxidation in blueberry fruit.

    Science.gov (United States)

    Song, Fangyuan; Su, Hongyan; Yang, Nan; Zhu, Luying; Cheng, Jieshan; Wang, Lei; Cheng, Xianhao

    2016-11-01

    Myo-inositol metabolism in plant edible organs has become the focus of many recent studies because of its benefits to human health and unique functions in plant development. In this study, myo-inositol contents were analyzed during the development of two blueberry cultivars, cv 'Berkeley' and cv 'Bluecrop'. Furthermore, two VcMIPS 1/2 (Vaccinium corymbosum MIPS) genes, one VcIMP (Vaccinium corymbosum IMP) gene and one VcMIOX (Vaccinium corymbosum MIOX) gene were isolated for the first time from blueberry. The expression patterns of VcMIPS2, VcIMP and VcMIOX genes showed a relationship with the change profiles of myo-inositol content during fruit ripening. The results were further confirmed by the analyses of the enzyme activity. Results indicated that both myo-inositol biosynthesis and oxidation played important roles in determining of myo-inositol levels during the development of blueberry. To our knowledge, this report is the first to discuss myo-inositol levels in fruits in terms of biosynthesis and catabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Mitogenic stimuli and phosphatidylinositol (PI) turnover in cultured 3T3 fibroblasts

    International Nuclear Information System (INIS)

    Kohler, C.; Petersen, R.

    1986-01-01

    The hydrolysis of PI and polyphosphoinositides by phopholipase C is an early and rapid response to cell activation by a variety of neurotransmitters, hormones, growth factors and pharmacological agonists. The authors have examined the role of PI turnover and the generation of second messengers (diacylglycerol and inositol trisphosphate) in the mitogenic response of cultured Balb/c and Swiss 3T3 cells to polypeptide growth factors. Cells were prelabelled with 3 H inositol for 18-20 hours, washed and suspended in Herpes + Li + buffer, and stimulated with platelet-derived growth factor (PDGF), vasopressin, insulin, and other growth factors. PI turnover was measured as the increase in total inositol phosphate (IP) production. IP1, IP2, and IP3 were characterized by sequential elution from a Dowex column. Partially purified PDGF produced a 2-4 fold stimulation of total IP production. This was seen as early as 30 seconds after stimulation and increased for up to 1-2 hours. Balb/c cells were more sensitive than Swiss cells to the mitogenic and PI effects of PDGF. Other mitogenic stimuli had differential effects on PI turnover. Vasopressin (4-400 ng/ml) markedly stimulated PI turnover (3-6 fold) in Swiss, but not Balb/c cells. Insulin (100 ng/ml - 10 μg/ml) increased total IP to a greater degree in Balb/c cells. Epidermal growth factor (10 ng/ml - 10 μg/ml) had no effect on PI turnover and fibroblast growth factor (10 ng/ml - 10 μg/ml) only stimulated at the higher concentrations in Swiss cells. Thrombin (1U/ml - 10 U/ml) produced a 1.5 - 2 fold stimulation in Balb/c cells. Thus, various polypeptide growth factors have differential effects on PI turnover depending on their mitogenic potential and the effector cell type

  14. A cell factory of Bacillus subtilis engineered for the simple bioconversion of myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Takenaka Shinji

    2011-09-01

    Full Text Available Abstract Background A stereoisomer of inositol, scyllo-inositol, is known as a promising therapeutic agent for Alzheimer's disease, since it prevents the accumulation of beta-amyloid deposits, a hallmark of the disease. However, this compound is relatively rare in nature, whereas another stereoisomer of inositol, myo-inositol, is abundantly available. Results Bacillus subtilis possesses a unique inositol metabolism involving both stereoisomers. We manipulated the inositol metabolism in B. subtilis to permit the possible bioconversion from myo-inositol to scyllo-inositol. Within 48 h of cultivation, the engineered strain was able to convert almost half of 10 g/L myo-inositol to scyllo-inositol that accumulated in the culture medium. Conclusions The engineered B. subtilis serves as a prototype of cell factory enabling a novel and inexpensive supply of scyllo-inositol.

  15. A cell factory of Bacillus subtilis engineered for the simple bioconversion of myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer's disease

    Science.gov (United States)

    2011-01-01

    Background A stereoisomer of inositol, scyllo-inositol, is known as a promising therapeutic agent for Alzheimer's disease, since it prevents the accumulation of beta-amyloid deposits, a hallmark of the disease. However, this compound is relatively rare in nature, whereas another stereoisomer of inositol, myo-inositol, is abundantly available. Results Bacillus subtilis possesses a unique inositol metabolism involving both stereoisomers. We manipulated the inositol metabolism in B. subtilis to permit the possible bioconversion from myo-inositol to scyllo-inositol. Within 48 h of cultivation, the engineered strain was able to convert almost half of 10 g/L myo-inositol to scyllo-inositol that accumulated in the culture medium. Conclusions The engineered B. subtilis serves as a prototype of cell factory enabling a novel and inexpensive supply of scyllo-inositol. PMID:21896210

  16. Carbachol-induced phosphoinositide turnover in NCB-20 cells

    International Nuclear Information System (INIS)

    Chuang, D.M.; Dillon-Carter, O.

    1986-01-01

    NCB-20 cells (fetal Chinese hamster brain cell x neuroblastoma hybrids) have been shown to contain a variety of neurotransmitter receptors. The authors now report that this cloned cell line also contains acetylcholne receptors which are linked to phospholipase C. Confluent cell cultures were preincubated with 3 H-myo-inositol to label endogenous phosphoinositide (PI) and the accumulation of a PI metabolite, inositol monophosphate (IP 1 ), was measured in the presence of LiCl. Carbachol increased IP 1 ), accumulation be more than 400% with a EC 50 of about 50 μM. Acetylcholine and muscarine were also effective, whereas oxotremorine and McN-A-343 were weak in both potency and efficacy. The carbachol-induced IP 1 accumulation was completely blocked by atropine (Ki approx. 0.6 nM) and pirenzepine (Ki approx. 15 nM). The presence of KCl was not required for the carbachol-induced effect. The formation of inositol bis- and triphosphate was also increased carbachol; these increases occurred earlier but were of much smaller magnitude. Pretreatment of cells with 4 β-phorbol dibutyrate or 4 β-phorbol myristate acetate was found to attenuate the carbachol-induced formation of IP 1 (IC 50 in the low nanomolar concentration ranges), however 4 β-phorbol, the biologically inactive phorbol ester, was ineffective in causing this attenuation. These results suggest a feedback inhibition of PI turnover in NCB-20 cells through the action of protein kinase C

  17. Liquid Crystal Gel Reduces Age Spots by Promoting Skin Turnover

    OpenAIRE

    Mina Musashi; Ariella Coler-Reilly; Teruaki Nagasawa; Yoshiki Kubota; Satomi Kato; Yoko Yamaguchi

    2014-01-01

    Studies have shown that liquid crystals structurally resembling the intercellular lipids in the stratum corneum can beneficially affect the skin when applied topically by stimulating the skin’s natural regenerative functions and accelerating epidermal turnover. In the present study, the effects of applying low concentrations of a liquid crystal gel of our own creation were evaluated using epidermal thickening in mouse skin as an assay for effective stimulation of epidermal turnover. A liquid ...

  18. The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry).

    Science.gov (United States)

    Thomas, Mark P; Mills, Stephen J; Potter, Barry V L

    2016-01-26

    Cell signaling via inositol phosphates, in particular via the second messenger myo-inositol 1,4,5-trisphosphate, and phosphoinositides comprises a huge field of biology. Of the nine 1,2,3,4,5,6-cyclohexanehexol isomers, myo-inositol is pre-eminent, with "other" inositols (cis-, epi-, allo-, muco-, neo-, L-chiro-, D-chiro-, and scyllo-) and derivatives rarer or thought not to exist in nature. However, neo- and d-chiro-inositol hexakisphosphates were recently revealed in both terrestrial and aquatic ecosystems, thus highlighting the paucity of knowledge of the origins and potential biological functions of such stereoisomers, a prevalent group of environmental organic phosphates, and their parent inositols. Some "other" inositols are medically relevant, for example, scyllo-inositol (neurodegenerative diseases) and d-chiro-inositol (diabetes). It is timely to consider exploration of the roles and applications of the "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo series. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Role of Inositol Phosphosphingolipid Phospholipase C1, the Yeast Homolog of Neutral Sphingomyelinases in DNA Damage Response and Diseases

    Directory of Open Access Journals (Sweden)

    Kaushlendra Tripathi

    2015-01-01

    Full Text Available Sphingolipids play a very crucial role in many diseases and are well-known as signaling mediators in many pathways. Sphingolipids are produced during the de novo process in the ER (endoplasmic reticulum from the nonsphingolipid precursor and comprise both structural and bioactive lipids. Ceramide is the central core of the sphingolipid pathway, and its production has been observed following various treatments that can induce several different cellular effects including growth arrest, DNA damage, apoptosis, differentiation, and senescence. Ceramides are generally produced through the sphingomyelin hydrolysis and catalyzed by the enzyme sphingomyelinase (SMase in mammals. Presently, there are many known SMases and they are categorized into three groups acid SMases (aSMases, alkaline SMases (alk-SMASES, and neutral SMases (nSMases. The yeast homolog of mammalians neutral SMases is inositol phosphosphingolipid phospholipase C. Yeasts generally have inositol phosphosphingolipids instead of sphingomyelin, which may act as a homolog of mammalian sphingomyelin. In this review, we shall explain the structure and function of inositol phosphosphingolipid phospholipase C1, its localization inside the cells, mechanisms, and its roles in various cell responses during replication stresses and diseases. This review will also give a new basis for our understanding for the mechanisms and nature of the inositol phosphosphingolipid phospholipase C1/nSMase.

  20. Spectroscopic and chemical reactivity analysis of D-Myo-Inositol ...

    Indian Academy of Sciences (India)

    Devendra P Mishra

    2017-06-20

    Jun 20, 2017 ... and leguminosae plants, has been reported to pos- sess insulin-like properties. Although the hypoglycemic activity of D-Myo-Inositol was recognized in recent years, the molecular mechanism of D-Myo-Inositol in the treatment of diabetes mellitus remains unclear. Diabetes mellitus is a complex disease that ...

  1. The emerging roles of inositol pyrophosphates in eukaryotic cell ...

    Indian Academy of Sciences (India)

    2015-08-13

    Aug 13, 2015 ... Inositol phosphate metabolism is well conserved from yeast to humans (Irvine and Schell 2001) ... simple metabolic pathway with a single enzyme for each step of inositol phosphate synthesis, whereas ..... response to UV stress, mammalian IP6K1 synthesizes IP7 that further activates the E3 ubiquitin ligase ...

  2. Characterization of inositol phosphates in carrot (Daucus carota L.) cells

    International Nuclear Information System (INIS)

    Rincon, M.; Chen, Q.; Boss, W.F.

    1989-01-01

    We have shown previously that inositol-1,4,5-trisphosphate (IP 3 ) stimulates an efflux of 45 Ca 2+ from fusogenic carrot protoplasts. In light of these results, we suggested that IP 3 might serve as a second messenger for the mobilization of intracellular Ca 2+ in higher plant cells. To determine whether or not IP 3 and other inositol phosphates were present in the carrot cells, the cells were labeled with myo-[2- 3 H]inositol for 18 hours and extracted with ice-cold 10% trichloroacetic acid. The inositol metabolites were separated by anion exchange chromatography and by paper electrophoresis. We found that [ 3 H]inositol metabolites coeluted with inositol bisphosphate (IP 2 ) and IP 3 when separated by anion exchange chromatography. However, we could not detect IP 2 or IP 3 when the inositol metabolites were analyzed by paper electrophoresis even though the polyphosphoinositides, which are the source of IP 2 and IP 3 , were present in these cells. Thus, [ 3 H]inositol metabolites other than IP 2 and IP 3 had coeluted on the anion exchange columns. The data indicate that either IP 3 is rapidly metabolized or that it is not present at a detectable level in the carrot cells

  3. Inositol and human reproduction. From cellular metabolism to clinical use.

    Science.gov (United States)

    Milewska, Ewa M; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Alessandro D

    2016-09-01

    Inositol is an organic compound of high biological importance that is widely distributed in nature. It belongs to the sugar family and is mainly represented by its two dominant stereoisomers: myo-inositol and D-chiro-inositol that are found in the organism in the physiological serum ratio 40:1. Inositol and its derivatives are important components of the structural phospholipids of the cell membranes and are precursors of the second messengers of many metabolic pathways. A high concentration of myoinositol is found in the follicular fluid and in semen. Inositol deficiency and the impairment of the inositol-dependent pathways may play an important role in the pathogenesis of insulin resistance and hypothyroidism. The results of the research also point out the potential beneficial role of inositol supplementation in polycystic ovarian syndrome and in the context of assisted reproduction technologies and in vitro fertilization. The main aim of the article is to overview the major inositol-dependent metabolic pathways and to discuss its importance for reproduction.

  4. G-proteins and the inositol cycle in Dictyostelium discoideum

    NARCIS (Netherlands)

    Bominaar, Anthony; van der Kaay, Jeroen; Kesbeke, F.; Snaarjagalska, BE.; van Haastert, Peter; MILLIGAN, G; WAKELAM, MJO; KAY, J

    1990-01-01

    The inositol cycle in Dictyostelium disocideum was studied both in vitro and in vivo. The results are compared to the inositol cycle as it is known from higher eukaryotes. Although there is a strong resemblance the cycles are different at some essential points. In comparison to higher eukaryotes, in

  5. Kinetic analysis of guanosine 5'-O-(3-thiotriphosphate) effects on phosphatidylinositol turnover in NRK cell homogenates

    International Nuclear Information System (INIS)

    Chahwala, S.B.; Fleischman, L.F.; Cantley, L.

    1987-01-01

    Addition of the guanine nucleotide analogue guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to [ 3 H]inositol-labeled NRK cell homogenates resulted in rapid breakdown of cellular polyphosphoinositides. GTP gamma S stimulated phospholipase C, resulting in a more than 4-fold increase in the hydrolysis rates of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bis(phosphate) (PIP2). No significant effect of GTP gamma S on direct phosphatidylinositol (PI) hydrolysis was detected. There was an increase in water-soluble inositols, with inositol tris(phosphate) (IP3) levels increasing at least 10 times over the decrease seen in PIP2, indicating that PIP kinase activity was also accelerated following GTP gamma S addition. Inositol 1,4,5-tris(phosphate) peaked rapidly after GTP gamma S addition (less than 2 min) while inositol 1,3,4-tris-(phosphate) was produced more slowly and leveled off after approximately 10 min. The differential equations describing conversion between intermediates in the PI turnover pathway were solved and fitted to data obtained from both [ 3 H]inositol and [ 32 P]phosphate fluxes by nonlinear least-squares analysis. GTP gamma S effects on the pseudo-first-order rate constants for the lipase, kinase, and phosphatase steps were determined from the analysis. From these measurements it can be estimated that, in the presence of GTP gamma S and calcium buffered to 130 nM, hydrolysis of PIP2 accounts for at least 10 times as much diacylglycerol as direct PI breakdown despite the 100-fold excess of PI over PIP2. From the kinetic model it is predicted that small changes in the activities of PI and PIP kinases can have large but different effects on the level of IP3 and diacylglycerol following GTP gamma S addition. These results argue that regulation of PI and PIP kinases may be important for determining both cellular IP3 and diacylglycerol levels

  6. Avifauna: Turnover on Islands.

    Science.gov (United States)

    Mayr, E

    1965-12-17

    The percentage of endemic species of birds on islands increases with island area at a double logarithmic rate. This relation is apparently due to extinction, which is more rapid the smaller the island. The turnover resulting from extinction and replacement appears to be far more rapid than hitherto suspected.

  7. Managing teacher turnover

    African Journals Online (AJOL)

    Erna Kinsey

    tion and training costs as well as loss of productivity while the newly hired teacher comes up to speed (cf. Carrel et al., 1998:572; Special. Reports, 1999:1). Ingersoll (2002:4) postulates that staffing problems are created when employees leave the organisation and have to be replaced, especially since teacher turnover is ...

  8. Managing teacher turnover

    African Journals Online (AJOL)

    Erna Kinsey

    retention and thus attrition is a function of teachers' personal characte- ristics, educational preparation, initial commitment to teaching, quality of first teaching experience, social and professional integration into teaching and external influences. Khatri, Budhwar and Fern's study of employee turnover (1999) employs a model ...

  9. Predicting Turnover Intentions and Turnover Behavior: A Multivariate Analysis.

    Science.gov (United States)

    Parasuraman, Saroj

    1982-01-01

    Assessed the relative influence of personal, attitudinal, and behavioral variables on behavioral intentions and voluntary turnover among nonsupervisory plant workers. Results show that personal variables have little direct effect on turnover; rather, their influence on turnover is channeled through their effects on behavioral intentions. (Author)

  10. Desumoylation of the Endoplasmic Reticulum Membrane VAP Family Protein Scs2 by Ulp1 and SUMO Regulation of the Inositol Synthesis Pathway

    Science.gov (United States)

    Felberbaum, Rachael; Wilson, Nicole R.; Cheng, Dongmei; Peng, Junmin

    2012-01-01

    Posttranslational protein modification by the ubiquitin-like SUMO protein is critical to eukaryotic cell regulation, but much remains unknown regarding its operation and substrates. Here we report that specific mutations in the Saccharomyces cerevisiae Ulp1 SUMO protease, including its coiled-coil (CC) domain, lead to the accumulation of distinct sumoylated proteins in vivo. A prominent ∼50-kDa sumoylated protein accumulates in a Ulp1 CC mutant. The protein was identified as Scs2, an endoplasmic reticulum (ER) membrane protein that regulates phosphatidylinositol synthesis and lipid trafficking. Mutation of lysine 180 of Scs2 abolishes its sumoylation. Notably, impairment of either cellular sumoylation or cellular desumoylation mechanisms inhibits cell growth in the absence of inositol and exacerbates the inositol auxotrophy caused by deletion of SCS2. Mutants lacking the Ulp2 SUMO protease are the most severely affected, and this defect was traced to the mutants' impaired ability to induce transcription of INO1, which encodes the rate-limiting enzyme of inositol biosynthesis. Conversely, inositol starvation induces a striking change in the profiles of total cellular SUMO conjugates. These results provide the first evidence of cross-regulation between the SUMO and inositol pathways, including the sumoylation of an ER membrane protein central to phospholipid synthesis and phosphoinositide signaling. PMID:22025676

  11. Inositol-deficient food augments a behavioral effect of long-term lithium treatment mediated by inositol monophosphatase inhibition: an animal model with relevance for bipolar disorder.

    Science.gov (United States)

    Shtein, Liza; Agam, Galila; Belmaker, R H; Bersudsky, Yuly

    2015-04-01

    Lithium treatment in rodents markedly enhances cholinergic agonists such as pilocarpine. This effect can be reversed in a stereospecific manner by administration of inositol, suggesting that the effect of lithium is caused by inositol monophosphatase inhibition and consequent inositol depletion. If so, inositol-deficient food would be expected to enhance lithium effects. Inositol-deficient food was prepared from inositol-free ingredients. Mice with a homozygote knockout of the inositol monophosphatase 1 gene unable to synthesize inositol endogenously and mimicking lithium-treated animals were fed this diet or a control diet. Lithium-treated wild-type animals were also treated with the inositol-deficient diet or control diet. Pilocarpine was administered after 1 week of treatment, and behavior including seizures was assessed using rating scale. Inositol-deficient food-treated animals, both lithium treated and with inositol monophosphatase 1 knockout, had significantly elevated cholinergic behavior rating and significantly increased or earlier seizures compared with the controls. The effect of inositol-deficient food supports the role of inositol depletion in the effects of lithium on pilocarpine-induced behavior. However, the relevance of this behavior to other more mood-related effects of lithium is not clear.

  12. Determination of inositol phosphate ester in lake sediments

    International Nuclear Information System (INIS)

    Weimer, W.C.; Armstrong, D.E.

    1977-01-01

    A procedure for the determination of the total inositol polyphosphate content of lake sediments is presented and evaluated. This technique involves extraction with NaOH, cleanup of the extract, and isolation and identification of two groups of inositol phosphate esters by ion-exchange chromatography. Radioisotope dilution is employed to correct for losses during the extraction, cleanup and isolation steps. Recoveries of the radiotracer inositol phosphates have averaged 85% during the analysis of approximately 40 calcareous and non-calcareous sediment samples and more than 20 soil samples

  13. Primary Klebsiella identification with MacConkey-inositol-carbenicillin agar.

    Science.gov (United States)

    Bagley, S T; Seidler, R J

    1978-09-01

    MacConkey-inositol-carbenicillin agar has successfully been used as a primary selective medium for Klebsiella enumeration. With pure cultures, nearly 100% recovery of Klebsiella was observed by membrane filtration. With environmental samples using membrane filtration, 95% of typical pink- to red-colored colonies were verified as Klebsiella, as opposed to only 1% of yellow background colonies. Recovery of Klebsiella on MacConkey-inositol-carbenicillin agar was as good or better than on mEndo agar LES (Difco Laboratories). Recovery and percent colony confirmation with MacConkey-inositol-carbenicillin agar were greater than for other proposed Klebsiella selective media.

  14. Chemoattractant and guanosine 5'-[γ-thio]triphosphate induce the accumulation of inositol 1,4,5-trisphosphate in Dictyostelium cells that are labelled with [3H]inositol by electroporation

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Vries, Martinus J. de; Penning, Louis C.; Roovers, Edwin; Kaay, Jeroen van der; Erneux, Christophe; Lookeren Campagne, Michiel M. van

    1989-01-01

    The analysis of the inositol cycle in Dictyostelium discoideum cells is complicated by the limited uptake of [3H]inositol (0.2% of the applied radioactivity in 6 h), and by the conversion of [3H]inositol into water-soluble inositol metabolites that are eluted near the position of inositol

  15. Seasonal groundwater turnover

    OpenAIRE

    Nordell, Bo; Engström, Maria

    2006-01-01

      Seasonal air temperature variations and corresponding changes in groundwater temperature cause convective movements in groundwater similar to the seasonal turnover in lakes. Numerical simulations were performed to investigate the natural conditions for thermally driven groundwater convection to take place. Thermally driven convection could be triggered by a horizontal groundwater flow, Convection then starts at a considerably lower Rayleigh number (Ra) than the general critical Rayleigh ...

  16. Neurotransmitter-stimulated inositol phosphate accumulation in hippocampal slices

    International Nuclear Information System (INIS)

    Labarca, R.; Janowsky, A.; Paul, S.M.

    1987-01-01

    The agonist-induced accumulation of [ 3 H]IP in the presence of lithium represents a sensitive method for studying a number of receptor-mediated events in brain. In the presence of lithium, receptor-mediated [ 3 H]IP3 formation in brain is difficult to demonstrate. It is possible that lithium itself may prevent the formation if IP3 and, thus, the presence of lithium in the incubation may account for such a discrepancy. It is likely that the effects of lithium on the PI cascade are more complex then previously envisioned. The recent identification of the inositol polyphosphates, myo-inositol 1,3,4-trisphosphate and myo-inositol 1,3,4,5-tetrakisphosphate, indicates that other inositol phosphates need to be considered in future studies of receptor-mediated PI metabolism

  17. Has Inositol Played Any Role in the Origin of Life?

    OpenAIRE

    Saiardi, Adolfo

    2017-01-01

    Phosphorus, as phosphate, plays a paramount role in biology. Since phosphate transfer reactions are an integral part of contemporary life, phosphate may have been incorporated into the initial molecules at the very beginning. To facilitate the studies into early phosphate utilization, we should look retrospectively to phosphate-rich molecules present in today?s cells. Overlooked by origin of life studies until now, inositol and the inositol phosphates, of which some species possess more phosp...

  18. Is inositol (1,3,4,5)-tetrakisphosphate a new second messenger?

    International Nuclear Information System (INIS)

    Hansen, C.A.; Williamson, J.R.

    1986-01-01

    Hormone-stimulated hydrolysis of inositol (Ins) lipids results in the rapid formation of Ins(1,4,5)P 3 , the second messenger for intracellular Ca 2+ mobilization. Recently, a more polar inositol phosphate, Ins(1,3,4,5)P 4 as well as its probable hydrolysis product Ins(1,3,4)P 3 have been reported to accumulate in carbachol-stimulated brain slices. Vasopressin addition to hepatocytes prelabeled with [ 3 H]-Ins also showed a rapid increase of Ins(1,3,4,5)P 4 , which was similar to that of Ins(1,4,5)P 3 , while the accumulation of Ins(1,3,4)P 3 was slower. In order to examine whether Ins(1,3,4,5)P 4 has any functional effects on Ca 2+ homeostasis, it was synthesized enzymatically from [ 3 H]-Ins(1,4,5)P 3 using a partially purified phosphoinositol kinase activity from rat brain cortex. [ 3 H]-labeled inositol phosphates were separated by anion exchange chromatography and analyzed by HPLC using ammonium formate/phosphoric acid gradient elution. Preliminary experiments indicate that Ins(1,3,4,5)P 4 up to 10 μM does not release Ca 2+ from vesicular pools in saponin-permeabilized hepatocytes. It has a slight inhibitory effect on Ins(1,4,5)P 3 -induced Ca 2+ release. The effect of Ins(1,3,4,5)P 4 on plasma membrane Ca 2+ fluxes are presently being investigated

  19. The Inositol-3-Phosphate Synthase Biosynthetic Enzyme Has Distinct Catalytic and Metabolic Roles.

    Science.gov (United States)

    Frej, Anna D; Clark, Jonathan; Le Roy, Caroline I; Lilla, Sergio; Thomason, Peter A; Otto, Grant P; Churchill, Grant; Insall, Robert H; Claus, Sandrine P; Hawkins, Phillip; Stephens, Len; Williams, Robin S B

    2016-05-15

    Inositol levels, maintained by the biosynthetic enzyme inositol-3-phosphate synthase (Ino1), are altered in a range of disorders, including bipolar disorder and Alzheimer's disease. To date, most inositol studies have focused on the molecular and cellular effects of inositol depletion without considering Ino1 levels. Here we employ a simple eukaryote, Dictyostelium discoideum, to demonstrate distinct effects of loss of Ino1 and inositol depletion. We show that loss of Ino1 results in an inositol auxotrophy that can be rescued only partially by exogenous inositol. Removal of inositol supplementation from the ino1(-) mutant resulted in a rapid 56% reduction in inositol levels, triggering the induction of autophagy, reduced cytokinesis, and substrate adhesion. Inositol depletion also caused a dramatic generalized decrease in phosphoinositide levels that was rescued by inositol supplementation. However, loss of Ino1 triggered broad metabolic changes consistent with the induction of a catabolic state that was not rescued by inositol supplementation. These data suggest a metabolic role for Ino1 that is independent of inositol biosynthesis. To characterize this role, an Ino1 binding partner containing SEL1L1 domains (Q54IX5) and having homology to mammalian macromolecular complex adaptor proteins was identified. Our findings therefore identify a new role for Ino1, independent of inositol biosynthesis, with broad effects on cell metabolism. Copyright © 2016 Frej et al.

  20. myo-Inositol 1,3-acetals as early intermediates during the synthesis of cyclitol derivatives.

    Science.gov (United States)

    Gurale, Bharat P; Sardessai, Richa S; Shashidhar, Mysore S

    2014-11-18

    Synthetic sequences starting from commercially available myo-inositol necessarily involve protection-deprotection strategies of its six hydroxyl groups. Several strategies have been developed/attempted over the last several decades leading to the synthesis of naturally occurring phosphoinositols, their analogs, and cyclitol derivatives. Of late, myo-inositol 1,3-acetals, which can be obtained by the reductive cleavage of myo-inositol orthoesters have emerged as early intermediates for the synthesis of phosphorylated and other inositol derivatives. This mini-review is an attempt to illustrate the economy and convenience of using myo-inositol 1,3-acetals as early intermediates during syntheses from myo-inositol.

  1. Preparation of phosphatidyl[2-3H]inositol from yeast grown in medium containing myo[2-3H]inositol

    International Nuclear Information System (INIS)

    Graff, G.; Harlan, J.; Nahas, N.

    1982-01-01

    Phosphatidyl[2- 3 H]inositol was prepared from Saccharomyces cerevisiae (YSC-2), grown in synthetic medium containing myo[2- 3 H]inositol. Over 44 microCi (or 81%) of the radiolabeled inositol was taken up by the organism, with 34 microCi incorporated into phosphatidylinositol. Upon purification by silicic acid pressure liquid chromatography (MPLC), a final yield of 24 to 26 microCi of phosphatidyl[2- 3 H]inositol with a specific radioactivity of 40 X 10(3) dpm/nmole was obtained. The purified phosphatidyl[2- 3 H]inositol was found to be a suitable substrate for phospholipase C from human platelets

  2. How Employee Turnover Affects Productivity

    DEFF Research Database (Denmark)

    Eriksen, Bo

    Research on employee turnover suggests that turnover results in negative organization-level outcomes. This paper provides a firm-level analysis of the impact of the in- and outflows of human resources on productivity and how the presence of organizational slack resources moderates the effects...... of employee turnover. Drawing on a unique longitudinal dataset of 2,926 Danish manufacturing firms that combine individual-level data with firm-level data, the paper shows that job turnover has a substantial negative effect on total productivity but that the firm’s size, its capital intensity, and its age...

  3. Hypotonic Activation of the Myo-Inositol Transporter SLC5A3 in HEK293 Cells Probed by Cell Volumetry, Confocal and Super-Resolution Microscopy

    Science.gov (United States)

    Andronic, Joseph; Shirakashi, Ryo; Pickel, Simone U.; Westerling, Katherine M.; Klein, Teresa; Holm, Thorge; Sauer, Markus; Sukhorukov, Vladimir L.

    2015-01-01

    Swelling-activated pathways for myo-inositol, one of the most abundant organic osmolytes in mammalian cells, have not yet been identified. The present study explores the SLC5A3 protein as a possible transporter of myo-inositol in hyponically swollen HEK293 cells. To address this issue, we examined the relationship between the hypotonicity-induced changes in plasma membrane permeability to myo-inositol Pino [m/s] and expression/localization of SLC5A3. Pino values were determined by cell volumetry over a wide tonicity range (100–275 mOsm) in myo-inositol-substituted solutions. While being negligible under mild hypotonicity (200–275 mOsm), Pino grew rapidly at osmolalities below 200 mOsm to reach a maximum of ∼3 nm/s at 100–125 mOsm, as indicated by fast cell swelling due to myo-inositol influx. The increase in Pino resulted most likely from the hypotonicity-mediated incorporation of cytosolic SLC5A3 into the plasma membrane, as revealed by confocal fluorescence microscopy of cells expressing EGFP-tagged SLC5A3 and super-resolution imaging of immunostained SLC5A3 by direct stochastic optical reconstruction microscopy (dSTORM). dSTORM in hypotonic cells revealed a surface density of membrane-associated SLC5A3 proteins of 200–2000 localizations/μm2. Assuming SLC5A3 to be the major path for myo-inositol, a turnover rate of 80–800 myo-inositol molecules per second for a single transporter protein was estimated from combined volumetric and dSTORM data. Hypotonic stress also caused a significant upregulation of SLC5A3 gene expression as detected by semiquantitative RT-PCR and Western blot analysis. In summary, our data provide first evidence for swelling-mediated activation of SLC5A3 thus suggesting a functional role of this transporter in hypotonic volume regulation of mammalian cells. PMID:25756525

  4. Hypotonic activation of the myo-inositol transporter SLC5A3 in HEK293 cells probed by cell volumetry, confocal and super-resolution microscopy.

    Directory of Open Access Journals (Sweden)

    Joseph Andronic

    Full Text Available Swelling-activated pathways for myo-inositol, one of the most abundant organic osmolytes in mammalian cells, have not yet been identified. The present study explores the SLC5A3 protein as a possible transporter of myo-inositol in hyponically swollen HEK293 cells. To address this issue, we examined the relationship between the hypotonicity-induced changes in plasma membrane permeability to myo-inositol P ino [m/s] and expression/localization of SLC5A3. P ino values were determined by cell volumetry over a wide tonicity range (100-275 mOsm in myo-inositol-substituted solutions. While being negligible under mild hypotonicity (200-275 mOsm, P ino grew rapidly at osmolalities below 200 mOsm to reach a maximum of ∼ 3 nm/s at 100-125 mOsm, as indicated by fast cell swelling due to myo-inositol influx. The increase in P ino resulted most likely from the hypotonicity-mediated incorporation of cytosolic SLC5A3 into the plasma membrane, as revealed by confocal fluorescence microscopy of cells expressing EGFP-tagged SLC5A3 and super-resolution imaging of immunostained SLC5A3 by direct stochastic optical reconstruction microscopy (dSTORM. dSTORM in hypotonic cells revealed a surface density of membrane-associated SLC5A3 proteins of 200-2000 localizations/μm2. Assuming SLC5A3 to be the major path for myo-inositol, a turnover rate of 80-800 myo-inositol molecules per second for a single transporter protein was estimated from combined volumetric and dSTORM data. Hypotonic stress also caused a significant upregulation of SLC5A3 gene expression as detected by semiquantitative RT-PCR and Western blot analysis. In summary, our data provide first evidence for swelling-mediated activation of SLC5A3 thus suggesting a functional role of this transporter in hypotonic volume regulation of mammalian cells.

  5. Reflections on inositol(s) for PCOS therapy: steps toward success.

    Science.gov (United States)

    Nestler, John E; Unfer, Vittorio

    2015-07-01

    In polycystic ovary syndrome (PCOS) pathogenesis, both the insulin resistance and the related compensatory hyperinsulinemia are involved. Despite their similarities, Myo-inositol (MI) and d-chiro-inositol (DCI) play different roles in PCOS etiology and therapy. Indeed, in tissue such as the liver both molecules are involved in the insulin signaling, i.e. MI promotes glucose uptake and DCI glycogen synthesis. In reproductive tissue such as the ovary, MI regulates glucose uptake and follicle stimulating hormone (FSH) signaling, whereas DCI is devoted to the insulin-mediated androgen production. The new hypothesis on "DCI paradox" in the ovary has provided the key for a better understanding. Unlike other tissues, ovary is not insulin resistant, indeed because the epimerase enzyme, which converts MI to DCI, is insulin dependent, the "DCI paradox" hypothesis suggests that in the ovary of PCOS women, an increased epimerase activity leads to a DCI overproduction and MI depletion. This imbalance could be the cause of the poor oocyte quality and the impairment in the FSH signaling. Owing to this situation, the focal point is the administration of both MI and DCI in a proper ratio for treating PCOS. This topic, with several other "hot" issues, was the driving thread in the discussion between the two scientists.

  6. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

    Science.gov (United States)

    Sortino, Maria A.; Salomone, Salvatore; Carruba, Michele O.; Drago, Filippo

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios. PMID:28642705

  7. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

    Directory of Open Access Journals (Sweden)

    Maria A. Sortino

    2017-06-01

    Full Text Available Polycystic ovary syndrome (PCOS is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios.

  8. [The role of inositol deficiency in the etiology of polycystic ovary syndrome disorders].

    Science.gov (United States)

    Jakimiuk, Artur J; Szamatowicz, Jacek

    2014-01-01

    Inositol acts as a second messenger in insulin signaling pathway Literature data suggest inositol deficiency in insulin-resistant women with the polycystic ovary syndrome. Supplementation of myo-inisitol decreases insulin resistance as it works as an insulin sensitizing agent. The positive role of myo-inositol in the treatment of polycystic ovary syndrome has been of increased evidence recently The present review presents the effects of myo-inositol on the ovarian, hormonal and metabolic parameters in women with PCOS.

  9. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H

    1994-01-01

    Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture...... collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum...... after 2 weeks in the diaphyseal fractures and after 6 weeks in the condylar fractures. The degradation of type I collagen increased after 4 days and reached a maximum at 2 weeks in both groups. The interindividual variation was wide. On a group basis, the turnover of types I and III collagen had...

  10. Identification of Ononitol and O-methyl-scyllo-inositol in Pea Root Nodules

    DEFF Research Database (Denmark)

    Skøt, Leif; Egsgaard, Helge

    1984-01-01

    Ononitol (4-O-methyl-myo-inositol) and O-methyl-scyllo-inositol were identified in pea (Pisum sativum L.) root nodules formed by twoRhizobium leguminosarum strains. Ononitol was the major soluble carbohydrate in nodules formed by strain 1045 while O-methyl-scyllo-inositol and two unidentified com...

  11. Spina bifida and genetic factors related to myo-inositol, glucose, and zinc.

    NARCIS (Netherlands)

    Groenen, P.; Klootwijk, E.D.; Schijvenaars, M.M.V.A.P.; Straatman, H.M.P.M.; Mariman, E.C.M.; Franke, B.; Steegers-Theunissen, R.P.M.

    2004-01-01

    BACKGROUND: Myo-inositol, glucose and zinc and related genetic factors are suggested to be implicated in the etiology of spina bifida. We investigated the biochemical concentrations of these nutrients and polymorphisms in the myo-inositol transporter SLC5A11, myo-inositol synthase ISYNA1, and zinc

  12. Brain Inositol Is a Novel Stimulator for Promoting Cryptococcus Penetration of the Blood-Brain Barrier

    Science.gov (United States)

    Wang, Yina; Toffaletti, Dena L.; Eugenin, Eliseo; Perfect, John R.; Kim, Kee Jun; Xue, Chaoyang

    2013-01-01

    Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. The facts that human and animal brains contain abundant inositol and that Cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. In this study, we found that inositol plays an important role in Cryptococcus traversal across the blood-brain barrier (BBB) both in an in vitro human BBB model and in in vivo animal models. The capacity of inositol to stimulate BBB crossing was dependent upon fungal inositol transporters, indicated by a 70% reduction in transmigration efficiency in mutant strains lacking two major inositol transporters, Itr1a and Itr3c. Upregulation of genes involved in the inositol catabolic pathway was evident in a microarray analysis following inositol treatment. In addition, inositol increased the production of hyaluronic acid in Cryptococcus cells, which is a ligand known to binding host CD44 receptor for their invasion. These studies suggest an inositol-dependent Cryptococcus traversal of the BBB, and support our hypothesis that utilization of host-derived inositol by Cryptococcus contributes to CNS infection. PMID:23592982

  13. Kinetics of myo-inositol loading in women of reproductive age.

    NARCIS (Netherlands)

    Groenen, P.; Merkus, J.M.W.M.; Sweep, C.G.J.; Wevers, R.A.; Janssen, F.; Steegers-Theunissen, R.P.M.

    2003-01-01

    BACKGROUND: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age. METHODS: Five

  14. Inositol-P 6 induced structural changes in duck major haemoglobin ...

    African Journals Online (AJOL)

    The reactivities of 5,5'-Dithiobis (2-nitrobenzoate) with the sulphydryl groups of major haemoglobin of duck (Anas platyrhinchos) have been carried out in the presence of inositol hexakisphosphate, inositol-P6. The time course of the reaction is biphasic. The addition of inositol-P6 changed the pH dependence profile of the ...

  15. Analysis of myo-inositol hexakisphosphate hydrolysis by Bacillus phytase

    DEFF Research Database (Denmark)

    Kerovuo, J.; Rouvinen, J.; Hatzack, Frank-Andreas

    2000-01-01

    Phytic acid (myo-inositol hexakisphosphate, InsP(6)) hydrolysis by Bacillus phytase (PhyC) was studied. The enzyme hydrolyses only three phosphates from phytic acid. Moreover, the enzyme seems to prefer the hydrolysis of every second phosphate over that of adjacent ones. Furthermore, it is very...... likely that the enzyme has two alternative pathways for the hydrolysis of phytic acid, resulting in two different myo-inositol trisphosphate end products: Ins(2,4,6)P-8 and Ins(1,3,5)P-3. These results, together with inhibition studies with fluoride, vanadate, substrate and a substrate analogue, indicate...

  16. Radioautography of myo-inositol in cultured Fraxinus callus

    International Nuclear Information System (INIS)

    Wolter, K.E.; Murmanis, L.

    1977-01-01

    Radioautographs by light and electron microscopy of callus cells of green ash (Fraxinus pennsylvanica Marsh.) that had been fed low levels of the growth factor 3 H myo-inositol indicated an almost exclusive incorporation of the label into the cytoplasmic constituents. These results contrast with those from most other studies of incorporation in higher plants. The incorporation here of myo-inositol suggests that its prime function is the synthesis of cytoplasmic membrane systems of the cell rather than in the polysaccharide component of the primary wall. (author)

  17. Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives

    OpenAIRE

    Yap, Angeline; Nishiumi, Shin; Yoshida, Ken-ichi; Ashida, Hitoshi

    2007-01-01

    Some of inositol derivatives have been reported to help the action of insulin stimulating glucose uptake in skeletal muscle cells. Rat L6 myotubes were employed in an attempt to develop an in vitro model system for investigation of the possible insulin-like effect of eight inositol derivatives, namely allo-inositol, d-chiro-inositol l-chiro-inositol, epi-inositol, muco-inositol, myo-inositol, scyllo-inositol and d-pinitol. At a higher concentration of 1 mM seven inositol derivatives other tha...

  18. Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice.

    Science.gov (United States)

    Fu, Min; Song, Yang; Wen, Zhaoxia; Lu, Xingyi; Cui, Lianhua

    2016-05-12

    Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-β1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies.

  19. The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome.

    Science.gov (United States)

    Dinicola, Simona; Chiu, Tony T Y; Unfer, Vittorio; Carlomagno, Gianfranco; Bizzarri, Mariano

    2014-10-01

    PCOS is one of the most common endocrine disorders affecting women and it is characterized by a combination of hyper-androgenism, chronic anovulation, and insulin resistance. While a significant progress has recently been made in the diagnosis for PCOS, the optimal infertility treatment remains to be determined. Two inositol isomers, myo-inositol (MI) and D-chiro-inositol (DCI) have been proven to be effective in PCOS treatment, by improving insulin resistance, serum androgen levels and many features of the metabolic syndrome. However, DCI alone, mostly when it is administered at high dosage, negatively affects oocyte quality, whereas the association MI/DCI, in a combination reproducing the plasma physiological ratio (40:1), represents a promising alternative in achieving better clinical results, by counteracting PCOS at both systemic and ovary level. © 2014, The American College of Clinical Pharmacology.

  20. Dynamics of Adipocyte Turnover in Humans

    Energy Technology Data Exchange (ETDEWEB)

    Spalding, K; Arner, E; Westermark, P; Bernard, S; Buchholz, B; Bergmann, O; Blomqvist, L; Hoffstedt, J; Naslund, E; Britton, T; Concha, H; Hassan, M; Ryden, M; Frisen, J; Arner, P

    2007-07-16

    Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells is thought to be most important. We show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese and even under extreme conditions, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analyzing the integration of {sup 14}C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in obesity, suggesting a tight regulation of fat cell number that is independent of metabolic profile in adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.

  1. Perturbation of the Vacuolar ATPase: A NOVEL CONSEQUENCE OF INOSITOL DEPLETION.

    Science.gov (United States)

    Deranieh, Rania M; Shi, Yihui; Tarsio, Maureen; Chen, Yan; McCaffery, J Michael; Kane, Patricia M; Greenberg, Miriam L

    2015-11-13

    Depletion of inositol has profound effects on cell function and has been implicated in the therapeutic effects of drugs used to treat epilepsy and bipolar disorder. We have previously shown that the anticonvulsant drug valproate (VPA) depletes inositol by inhibiting myo-inositol-3-phosphate synthase, the enzyme that catalyzes the first and rate-limiting step of inositol biosynthesis. To elucidate the cellular consequences of inositol depletion, we screened the yeast deletion collection for VPA-sensitive mutants and identified mutants in vacuolar sorting and the vacuolar ATPase (V-ATPase). Inositol depletion caused by starvation of ino1Δ cells perturbed the vacuolar structure and decreased V-ATPase activity and proton pumping in isolated vacuolar vesicles. VPA compromised the dynamics of phosphatidylinositol 3,5-bisphosphate (PI3,5P2) and greatly reduced V-ATPase proton transport in inositol-deprived wild-type cells. Osmotic stress, known to increase PI3,5P2 levels, did not restore PI3,5P2 homeostasis nor did it induce vacuolar fragmentation in VPA-treated cells, suggesting that perturbation of the V-ATPase is a consequence of altered PI3,5P2 homeostasis under inositol-limiting conditions. This study is the first to demonstrate that inositol depletion caused by starvation of an inositol synthesis mutant or by the inositol-depleting drug VPA leads to perturbation of the V-ATPase. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Spectroscopic and chemical reactivity analysis of D-Myo-Inositol ...

    Indian Academy of Sciences (India)

    2017-06-20

    Jun 20, 2017 ... ... Pramana – Journal of Physics; Volume 89; Issue 1. Spectroscopic and chemical reactivity analysis of D-Myo-Inositol using quantum chemical approach and its experimental verification. DEVENDRA P MISHRA ANCHAL SRIVASTAVA R K SHUKLA. Special Issue Volume 89 Issue 1 July 2017 Article ID 12 ...

  3. Using inositol as a biocompatible ligand for efficient transgene expression

    Science.gov (United States)

    Zhang, Lei; Bellis, Susan L; Fan, Yiwen; Wu, Yunkun

    2015-01-01

    Transgene transfection techniques using cationic polymers such as polyethylenimines (PEIs) and PEI derivatives as gene vectors have shown efficacy, although they also have shortcomings. PEIs have decent DNA-binding capability and good cell internalization performance, but they cannot deliver gene payloads very efficiently to cell nuclei. In this study, three hyperbranched polyglycerol-polyethylenimine (PG6-PEI) polymers conjugated with myo-inositol (INO) molecules were developed. The three resulting PG6-PEI-INO polymers have an increased number of INO ligands per molecule. PG6-PEI-INO 1 had only 14 carboxymethyl INO (CMINO) units per molecule. PG6-PEI-INO 2 had approximately 130 CMINO units per molecule. PG6-PEI-INO 3 had as high as 415 CMINO units approximately. Mixing PG6-PEI-INO polymers with DNA produced compact nanocomposites. We then performed localization studies using fluorescent microscopy. As the number of conjugated inositol ligands increased in PG6-PEI-INO polymers, there was a corresponding increase in accumulation of the polymers within 293T cell nuclei. Transfection performed with spherical 293T cells yielded 82% of EGFP-positive cells when using PG6-PEI-INO 3 as the vehicle. Studies further revealed that extracellular adenosine triphosphate (eATP) can inhibit the transgene efficiency of PG6-PEI-INO polymers, as compared with PEI and PG6-PEI that were not conjugated with inositol. Our work unveiled the possibility of using inositol as an effective ligand for transgene expression. PMID:25926732

  4. The emerging roles of inositol pyrophosphates in eukaryotic cell ...

    Indian Academy of Sciences (India)

    2015-08-13

    Aug 13, 2015 ... results in synthesis of 5-IP7 from IP6, whereas a reduction in the ATP/ADP ratio ..... kinase activity under phosphate starved conditions to enable ..... weight gain. Cell 143 897–910. Chakraborty A, Kim S and Snyder SH 2011 Inositol pyrophos- phates as mammalian cell signals. Sci. Signal. 4 1–11. Choi K ...

  5. Spectroscopic and chemical reactivity analysis of D-Myo-Inositol ...

    Indian Academy of Sciences (India)

    Devendra P Mishra

    2017-06-20

    Jun 20, 2017 ... 'the silent killer' due to the number of patients and many chronic complications. Around 90% of the dia- ... favourable effect of D-Myo-Inositol on the treatment of disorders associated with insulin because of its ... holic fraction of anthocephalus chinensis leaves. It was purified over silica gel (flash 230–400 ...

  6. Metabolism of inositol 4-monophosphate in rat mammalian tissues

    International Nuclear Information System (INIS)

    Delvaux, A.; Dumont, J.E.; Erneux, C.

    1987-01-01

    Rat brain soluble fraction contains an enzymatic activity that dephosphorylates inositol 1,4-bisphosphate (Ins(1,4)P2). We have used anion exchange h.p.l.c. in order to identify the inositol monophosphate product of Ins(1,4)P2 hydrolysis (i.e. Ins(1)P1, Ins(4)P1 or both). When [ 3 H]Ins(1,4)P2 was used as substrate, we obtained an inositol monophosphate isomer that was separated from the co-injected standard [ 3 H]Ins(1)P1. This suggested an Ins(1,4)P21-phosphatase pathway leading to the production of the inositol 4-monophosphate isomer. The dephosphorylation of [ 32 P]Ins(4)P1 was measured in rat brain, liver and heart soluble fraction and was Li+-sensitive. Chromatography of the soluble fraction of a rat brain homogenate on DEAE-cellulose resolved a monophosphate phosphatase activity that hydrolyzed both [ 3 H]Ins(1)P1 and [4- 32 P]Ins(4)P1 isomers

  7. Using inositol as a biocompatible ligand for efficient transgene expression.

    Science.gov (United States)

    Zhang, Lei; Bellis, Susan L; Fan, Yiwen; Wu, Yunkun

    2015-01-01

    Transgene transfection techniques using cationic polymers such as polyethylenimines (PEIs) and PEI derivatives as gene vectors have shown efficacy, although they also have shortcomings. PEIs have decent DNA-binding capability and good cell internalization performance, but they cannot deliver gene payloads very efficiently to cell nuclei. In this study, three hyperbranched polyglycerol-polyethylenimine (PG6-PEI) polymers conjugated with myo-inositol (INO) molecules were developed. The three resulting PG6-PEI-INO polymers have an increased number of INO ligands per molecule. PG6-PEI-INO 1 had only 14 carboxymethyl INO (CMINO) units per molecule. PG6-PEI-INO 2 had approximately 130 CMINO units per molecule. PG6-PEI-INO 3 had as high as 415 CMINO units approximately. Mixing PG6-PEI-INO polymers with DNA produced compact nanocomposites. We then performed localization studies using fluorescent microscopy. As the number of conjugated inositol ligands increased in PG6-PEI-INO polymers, there was a corresponding increase in accumulation of the polymers within 293T cell nuclei. Transfection performed with spherical 293T cells yielded 82% of EGFP-positive cells when using PG6-PEI-INO 3 as the vehicle. Studies further revealed that extracellular adenosine triphosphate (eATP) can inhibit the transgene efficiency of PG6-PEI-INO polymers, as compared with PEI and PG6-PEI that were not conjugated with inositol. Our work unveiled the possibility of using inositol as an effective ligand for transgene expression.

  8. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H

    1994-01-01

    Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture....... The markers were the carboxy-terminal extension peptide of type I procollagen (PICP), the amino-terminal extension peptide of type III procollagen (PIIINP), and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP). The latter is a new serum marker of degradation of type I...... collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum...

  9. Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome.

    Science.gov (United States)

    Unfer, Vittorio; Porcaro, Giuseppina

    2014-09-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. It is characterized by chronic anovulation, hyperandrogenism, and insulin resistance. It is the main cause of infertility due to the menstrual dysfunction and metabolic disorders. Women with PCOS also have an increased cardiovascular risk because of dyslipidemia and insulin resistance. So far, we have a lot of information about the etiology of PCOS, and many steps forward have been made about the diagnosis of this syndrome, but there is still no certainty about the therapy. Myo-inositol (MI) and D-chiro-inositol, two inositol stereoisomers, have been proven to be effective in PCOS treatment. However, only MI has been shown to have beneficial effects on reproductive function, whereas the administration of MI/D-chiro-inositol, in the physiological plasma ratio (i.e., 40:1) ensures better clinical results, such as the reduction of insulin resistance, androgens' blood levels, cardiovascular risk and regularization of menstrual cycle with spontaneous ovulation.

  10. KECENDERUNGAN KEPUASAN KERJA SEBAGAI TRIGGER TURNOVER

    OpenAIRE

    Raditya Adi Saputra

    2017-01-01

    The purpose of this study are: (1) To determine the effect of job satisfaction on turnover intention; (2) To determine the effect of work stress on turnover intention; (3) To determine the effect of compensation on turnover intention; (4) To determine the effect of organizational climate on turnover intention; and (5) To determine the stress of work, compensation, organizational climate and job satisfaction effect on turnover intention. The population in this study are employees of the Coo...

  11. Effects of inositol, inositol-generating phytase B applied alone, and in combination with 6-phytase A to phosphorus-deficient diets on laying performance, eggshell quality, yolk cholesterol, and fatty acid deposition in laying hens.

    Science.gov (United States)

    Zyla, K; Mika, M; Duliński, R; Swiatkiewicz, S; Koreleski, J; Pustkowiak, H; Piironen, J

    2012-08-01

    Phytase B, a product of Aspergillus niger phyB gene expressed in Trichoderma reesei, which increased myo-inositol concentrations in 20 mM sodium phytate solution 7.5-fold during 120-min incubation, a combination of phytase B with 6-phytase A, and pure myo-inositol were tested as feed supplements in Bovans Brown laying hens. In the 2-factorial experiment (2×5), birds from wk 50 to 62 were fed 2 basal diets, corn-soybean (CSM) or wheat-soybean (WSM), using 12 one-hen cages per treatment. For both basal diets, the dietary treatments included negative control (0.08% nonphytate P in CSM, 0.13% nonphytate P in WSM; NC); internal control groups, NC+0.04% nonphytate P from monocalcium phosphate, MCP (IC); NC+0.1% of myo-inositol (Inos), NC+phytase B at 1,300 units of phytase B-acid phosphatase activity (AcPU)/kg (PhyB), NC+phytase B at 1,300 AcPU/kg+6-phytase A at 300 FTU/kg (PhyA+B). Feed intake, laying performance, and eggshell quality were determined. The total lipid and cholesterol contents as well as fatty acid profile were assessed in egg yolks collected from hens fed CSM diets, as was fatty acid profile. The hens fed the WSM diet consumed significantly more feed, laid a higher mass of eggs daily with higher mean weights, and had a higher hen-day egg production than the birds receiving the CSM diets. Similarly, higher values for yolk weights, shell weights, shell thickness, shell density, and breaking strengths were determined in the eggs laid by the hens fed the WSM diets. In hens fed either the CSM diets with phytase B alone, or in combination with 6-phytase A, enhanced feed intakes, egg mass, and hen-day egg production were recorded. Phytases also enhanced the eggshell quality parameters in the hens fed both variants of the diets. Phytase B alone, or in combination with 6-phytase A, reduced the total lipid and cholesterol concentrations in egg yolks collected from the hens fed the CSM diets, whereas the combination of both phytases improved the n-6:n-3

  12. Two Major Inositol Transporters and Their Role in Cryptococcal Virulence ▿ †

    Science.gov (United States)

    Wang, Yina; Liu, Tong-bao; Delmas, Guillaume; Park, Steven; Perlin, David; Xue, Chaoyang

    2011-01-01

    Cryptococcus neoformans is an AIDS-associated human fungal pathogen and the most common cause of fungal meningitis, with a mortality rate over 40% in AIDS patients. Significant advances have been achieved in understanding its disease mechanisms. Yet the underlying mechanism of a high frequency of cryptococcal meningitis remains unclear. The existence of high inositol concentrations in brain and our earlier discovery of a large inositol transporter (ITR) gene family in C. neoformans led us to investigate the potential role of inositol in Cryptococcus-host interactions. In this study, we focus on functional analyses of two major ITR genes to understand their role in virulence of C. neoformans. Our results show that ITR1A and ITR3C are the only two ITR genes among 10 candidates that can complement the growth defect of a Saccharomyces cerevisiae strain lacking inositol transporters. Both S. cerevisiae strains heterologously expressing ITR1A or ITR3C showed high inositol uptake activity, an indication that they are major inositol transporters. Significantly, itr1a itr3c double mutants showed significant virulence attenuation in murine infection models. Mutating both ITR1A and ITR3C in an ino1 mutant background activates the expression of several remaining ITR candidates and does not show more severe virulence attenuation, suggesting that both inositol uptake and biosynthetic pathways are important for inositol acquisition. Overall, our study provides evidence that host inositol and fungal inositol transporters are important for Cryptococcus pathogenicity. PMID:21398509

  13. Comparison of S. cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site

    Science.gov (United States)

    Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; Kenniston, Jon A.; Mendrola, Jeannine M.; Ferguson, Kathryn M.; Lemmon, Mark A.

    2015-01-01

    SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence. PMID:25620000

  14. Histone turnover within nonproliferating cells

    International Nuclear Information System (INIS)

    Commerford, S.L.; Carsten, A.L.; Cronkite, E.P.

    1982-01-01

    The turnover of DNA and histones in the livers and brains of mice has been determined. These mice had been exposed to constant levels of tritiated water from conception until they were 8 months old. At this point, exposure to tritium was discontinued, and the tritium remaining in DNA and histones was measured at various intervals afterward. The half-lives calculated for these components (with 95% confidence limits given in parentheses) were 117 (85 to 188) days for liver histone, 318 (241 to 466) days for liver DNA, 159 (129 to 208) days for brain histone and 593 (376 to 1406) days for brain DNA. The difference between histone and DNA turnover is statistically significant for both tissues and indicates that histone turnover within tissues cannot be solely accounted for by cell turnover within the tissue but also must include histone turnover within living cells. The half-life of histone within cells is estimated to be 117 (88 to 178) days in liver and 223 (187 to 277) days in brain

  15. Inositol hexa-phosphate: a potential chelating agent for uranium

    Energy Technology Data Exchange (ETDEWEB)

    Cebrian, D.; Tapia, A.; Real, A.; Morcillo, M.A. [Radiobiology Laboratory, Radiation Dosimetry Unit, Department of Environment, CIEMAT, Avda Complutense 22, 28040 Madrid (Spain)

    2007-07-01

    Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexa-phosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexa-phosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo. (authors)

  16. Inositol hexa-phosphate: a potential chelating agent for uranium

    International Nuclear Information System (INIS)

    Cebrian, D.; Tapia, A.; Real, A.; Morcillo, M.A.

    2007-01-01

    Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexa-phosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexa-phosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo. (authors)

  17. Inositol trisphosphate receptor in higher plants: is it real?

    Czech Academy of Sciences Publication Activity Database

    Krinke, Ondřej; Novotná, Z.; Valentová, O.; Martinec, Jan

    2007-01-01

    Roč. 58, č. 3 (2007), s. 361-376 ISSN 0022-0957 R&D Projects: GA MŠk(CZ) LC06034 Institutional research plan: CEZ:AV0Z50380511 Source of funding: V - iné verejné zdroje Keywords : Ca2+ signalling * higher plants * inositol trisphosphate receptor Subject RIV: EF - Botanics Impact factor: 3.917, year: 2007

  18. High ionic strength or presence of inositol hexakisphosphate ...

    African Journals Online (AJOL)

    From kinetic data collected at high salt concentration, and in the presence of inositol hexakisphosphate, it is shown that the pKa of the sulphydryl increases to ca 9 and 7.7, respectively. Under these conditions, CysH3(125)β ceases to be an acid Bohr group. KEY WORDS: Haemoglobin, CysH3(125)β, pKa, Bohr effect, ...

  19. Inositol pyrophosphates and their unique metabolic complexity: analysis by gel electrophoresis.

    Directory of Open Access Journals (Sweden)

    Oriana Losito

    Full Text Available Inositol pyrophosphates are a recently characterized cell signalling molecules responsible for the pyrophosphorylation of protein substrates. Though likely involved in a wide range of cellular functions, the study of inositol pyrophosphates has suffered from a lack of readily available methods for their analysis.We describe a novel, sensitive and rapid polyacrylamide gel electrophoresis (PAGE-based method for the analysis of inositol pyrophosphates. Using 4',6-diamidino-2-phenylindole (DAPI and Toluidine Blue we demonstrate the unequivocal detection of various inositol pyrophosphate species.The use of the PAGE-based method reveals the likely underestimation of inositol pyrophosphates and their signalling contribution in cells when measured via traditional HPLC-based techniques. PAGE-based analyses also reveals the existence of a number of additional, previously uncharacterised pyrophosphorylated inositol reaction products, defining a more complex metabolism associated with the catalytically flexible kinase class responsible for the production of these highly energetic cell signalling molecules.

  20. Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial.

    Science.gov (United States)

    Santamaria, Angelo; Di Benedetto, Antonino; Petrella, Elisabetta; Pintaudi, Basilio; Corrado, Francesco; D'Anna, Rosario; Neri, Isabella; Facchinetti, Fabio

    2016-10-01

    To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15-0.70). Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.

  1. Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery.

    Science.gov (United States)

    Li, Cecilia; Lev, Sophie; Saiardi, Adolfo; Desmarini, Desmarini; Sorrell, Tania C; Djordjevic, Julianne T

    2016-09-06

    Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans , the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1)-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK), which are involved in synthesizing inositol polyphosphates (IP). We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P) and pyrophosphate (PP) groups covalently attached at different positions. This review focuses on (1) the characterization of the Plc1/IPK pathway in C. neoformans ; (2) the identification of PP-IP₅ (IP₇) as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3) why IPK enzymes represent suitable candidates for drug development.

  2. Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

    Directory of Open Access Journals (Sweden)

    Cecilia Li

    2016-09-01

    Full Text Available Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK, which are involved in synthesizing inositol polyphosphates (IP. We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P and pyrophosphate (PP groups covalently attached at different positions. This review focuses on (1 the characterization of the Plc1/IPK pathway in C. neoformans; (2 the identification of PP-IP5 (IP7 as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3 why IPK enzymes represent suitable candidates for drug development.

  3. Phosphorylation Regulates myo-Inositol-3-phosphate Synthase

    Science.gov (United States)

    Deranieh, Rania M.; He, Quan; Caruso, Joseph A.; Greenberg, Miriam L.

    2013-01-01

    myo-Inositol-3-phosphate synthase (MIPS) plays a crucial role in inositol homeostasis. Transcription of the coding gene INO1 is highly regulated. However, regulation of the enzyme is not well defined. We previously showed that MIPS is indirectly inhibited by valproate, suggesting that the enzyme is post-translationally regulated. Using 32Pi labeling and phosphoamino acid analysis, we show that yeast MIPS is a phosphoprotein. Mass spectrometry analysis identified five phosphosites, three of which are conserved in the human MIPS. Analysis of phosphorylation-deficient and phosphomimetic site mutants indicated that the three conserved sites in yeast (Ser-184, Ser-296, and Ser-374) and humans (Ser-177, Ser-279, and Ser-357) affect MIPS activity. Both S296A and S296D yeast mutants and S177A and S177D human mutants exhibited decreased enzymatic activity, suggesting that a serine residue is critical at that location. The phosphomimetic mutations S184D (human S279D) and S374D (human S357D) but not the phosphodeficient mutations decreased activity, suggesting that phosphorylation of these two sites is inhibitory. The double mutation S184A/S374A caused an increase in MIPS activity, conferred a growth advantage, and partially rescued sensitivity to valproate. Our findings identify a novel mechanism of regulation of inositol synthesis by phosphorylation of MIPS. PMID:23902760

  4. Synthesis of (±)-myo-inositol 4-methylenephosphonate via Rh-Catalyzed hydrogenation of vinylphosphonate.

    Science.gov (United States)

    Okauchi, Tatsuo; Nakamura, Shuya; Tsubaki, Kouta; Asakawa, Momoko; Kitamura, Mitsuru

    2017-08-07

    Phosphatidylinositol phosphate (PIP) synthetase is a promising target for the development of new anti-mycobacterium compounds. We previously reported that myo-inositol 1-methylenephosphonate showed inhibitory activity against PIP synthetase. Herein, we report the synthesis of unprotected myo-inositol 4-methylenephosphonate, a constitutional isomer of myo-inositol 1-methylenephosphonate and found that the stereoselective hydrogenation of vinylphosphonate proceeded via Rh catalysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. A structural investigation of the phosphatidyl inositols in mouse inflammatory peritoneal macrophages

    International Nuclear Information System (INIS)

    Shannon, P.V.R.; Petit, P.F.

    1983-01-01

    The incorporation of (2- 3 H)-myo-inositol into the phosphatidyl inositols of mouse inflammatory peritoneal macrophages gave labelled phospholipid from these cells. Chemical degradation followed by chromatographic comparison with unlabelled standards enabled confirmation of the myo-inositol-l (glyceryl-1-phosphate) structure. G.1.c.-mass spectrometry indicated that the principal fatty acids in the 1, 2-sn-diacy- glyceryl moiety were stearate, palmitate, linoleate, oleate and arachidonate. Incorporation of (13- 14 C)-arachidonic acid into the phosphatidyl inositols and enzymic hydrolysis with phospholipase A 2 showed that this acid is predominantly at the glyceryl -2-position (author)

  6. Biochemical markers of bone turnover

    International Nuclear Information System (INIS)

    Kim, Deog Yoon

    1999-01-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

  7. Biochemical markers of bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    1999-08-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays.

  8. Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.

    Science.gov (United States)

    Facchinetti, Fabio; Bizzarri, Mariano; Benvenga, Salvatore; D'Anna, Rosario; Lanzone, Antonio; Soulage, Christophe; Di Renzo, Gian Carlo; Hod, Moshe; Cavalli, Pietro; Chiu, Tony T; Kamenov, Zdravko A; Bevilacqua, Arturo; Carlomagno, Gianfranco; Gerli, Sandro; Oliva, Mario Montanino; Devroey, Paul

    2015-12-01

    In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Chronic Teacher Turnover in Urban Elementary Schools

    OpenAIRE

    Kacey Guin

    2004-01-01

    This study examines the characteristics of elementary schools that experience chronic teacher turnover and the impacts of turnover on a school’s working climate and ability to effectively function. Based on evidence from staff climate surveys and case studies, it is clear that high turnover schools face significant organizational challenges. Schools with high teacher turnover rates have difficulty planning and implementing a coherent curriculum and sustaining positive working relationships am...

  10. Inositol phospholipids regulate the guanine-nucleotide-exchange factor Tiam1 by facilitating its binding to the plasma membrane and regulating GDP/GTP exchange on Rac1.

    Science.gov (United States)

    Fleming, Ian N; Batty, Ian H; Prescott, Alan R; Gray, Alex; Kular, Gursant S; Stewart, Hazel; Downes, C Peter

    2004-09-15

    Binding of the Rac1-specific guanine-nucleotide-exchange factor, Tiam1, to the plasma membrane requires the N-terminal pleckstrin homology domain. In the present study, we show that membrane-association is mediated by binding of PtdIns(4,5)P(2) to the pleckstrin homology domain. Moreover, in 1321N1 astrocytoma cells, translocation of Tiam1 to the cytosol, following receptor-mediated stimulation of PtdIns(4,5)P(2) breakdown, correlates with decreased Rac1-GTP levels, indicating that membrane-association is required for GDP/GTP exchange on Rac1. In addition, we show that platelet-derived growth factor activates Rac1 in vivo by increasing PtdIns(3,4,5)P(3) concentrations, rather than the closely related lipid, PtdIns(3,4)P(2). Finally, the data demonstrate that PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3) bind to the same pleckstrin homology domain in Tiam1 and that soluble inositol phosphates appear to compete with lipids for this binding. Together, these novel observations provide strong evidence that distinct phosphoinositides regulate different functions of this enzyme, indicating that local concentrations of signalling lipids and the levels of cytosolic inositol phosphates will play crucial roles in determining its activity in vivo.

  11. Comparative Genomics of Pneumocystis Species Suggests the Absence of Genes for myo-Inositol Synthesis and Reliance on Inositol Transport and Metabolism

    Science.gov (United States)

    Sesterhenn, Thomas M.; Collins, Margaret S.; Welge, Jeffrey A.

    2014-01-01

    ABSTRACT In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P. murina, and P. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The underrepresentation of amino acid metabolism pathways compared to those in S. pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed for P. carinii and P. jirovecii and extended to P. murina. All three Pneumocystis species showed overrepresentation of the inositol phosphate metabolism pathway compared to that in the fission yeast. In addition to those known in S. pombe, four genes, encoding inositol-polyphosphate multikinase (EC 2.7.1.151), inositol-pentakisphosphate 2-kinase (EC 2.7.1.158), phosphoinositide 5-phosphatase (EC 3.1.3.36), and inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57), were identified in the two rodent Pneumocystis genomes, P. carinii and P. murina. The P. jirovecii genome appeared to contain three of these genes but lacked phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential for myo-inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol monophosphatase (INM1), were absent from all three genomes, suggesting that Pneumocystis species are inositol auxotrophs. In keeping with the need to acquire exogenous inositol, two genes with products homologous to fungal inositol transporters, ITR1 and ITR2, were identified in P. carinii and P. murina, while P. jirovecii contained only the ITR1 homolog. The ITR and inositol metabolism genes in P. murina and P. carinii were expressed during fulminant infection as determined by reverse transcriptase real-time PCR of cDNA from infected lung tissue. Supplementation of in vitro culture with inositol yielded significant improvement of the viability of P. carinii for days 7 through 14. PMID:25370490

  12. An In Vitro Enzyme System for the Production of myo-Inositol from Starch.

    Science.gov (United States)

    Fujisawa, Tomoko; Fujinaga, Shohei; Atomi, Haruyuki

    2017-08-15

    We developed an in vitro enzyme system to produce myo -inositol from starch. Four enzymes were used, maltodextrin phosphorylase (MalP), phosphoglucomutase (PGM), myo -inositol-3-phosphate synthase (MIPS), and inositol monophosphatase (IMPase). The enzymes were thermostable: MalP and PGM from the hyperthermophilic archaeon Thermococcus kodakarensis , MIPS from the hyperthermophilic archaeon Archaeoglobus fulgidus , and IMPase from the hyperthermophilic bacterium Thermotoga maritima The enzymes were individually produced in Escherichia coli and partially purified by subjecting cell extracts to heat treatment and removing denatured proteins. The four enzyme samples were incubated at 90°C with amylose, phosphate, and NAD + , resulting in the production of myo -inositol with a yield of over 90% at 2 h. The effects of varying the concentrations of reaction components were examined. When the system volume was increased and NAD + was added every 2 h, we observed the production of 2.9 g myo -inositol from 2.9 g amylose after 7 h, achieving gram-scale production with a molar conversion of approximately 96%. We further integrated the pullulanase from T. maritima into the system and observed myo -inositol production from soluble starch and raw potato with yields of 73% and 57 to 61%, respectively. IMPORTANCE myo -Inositol is an important nutrient for human health and provides a wide variety of benefits as a dietary supplement. This study demonstrates an alternative method to produce myo -inositol from starch with an in vitro enzyme system using thermostable maltodextrin phosphorylase (MalP), phosphoglucomutase (PGM), myo -inositol-3-phosphate synthase, and myo -inositol monophosphatase. By utilizing MalP and PGM to generate glucose 6-phosphate, we can avoid the addition of phosphate donors such as ATP, the use of which would not be practical for scaled-up production of myo -inositol. myo -Inositol was produced from amylose on the gram scale with yields exceeding 90

  13. Lipophagy: Connecting Autophagy and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Rajat Singh

    2012-01-01

    Full Text Available Lipid droplets (LDs, initially considered “inert” lipid deposits, have gained during the last decade the classification of cytosolic organelles due to their defined composition and the multiplicity of specific cellular functions in which they are involved. The classification of LD as organelles brings along the need for their regulated turnover and recent findings support the direct contribution of autophagy to this turnover through a process now described as lipophagy. This paper focuses on the characteristics of this new type of selective autophagy and the cellular consequences of the mobilization of intracellular lipids through this process. Lipophagy impacts the cellular energetic balance directly, through lipid breakdown and, indirectly, by regulating food intake. Defective lipophagy has been already linked to important metabolic disorders such as fatty liver, obesity and atherosclerosis, and the age-dependent decrease in autophagy could underline the basis for the metabolic syndrome of aging.

  14. Chloride secretagogues stimulate inositol phosphate formation in shark rectal gland tubules cultured in suspension

    International Nuclear Information System (INIS)

    Ecay, T.W.; Valentich, J.D.

    1991-01-01

    Neuroendocrine activation of transepithelial chloride secretion by shark rectal gland cells is associated with increases in cellular cAMP, cGMP, and free calcium concentrations. We report here on the effects of several chloride secretagogues on inositol phosphate formation in cultured rectal gland tubules. Vasoactive intestinal peptide (VIP), atriopeptin (AP), and ionomycin increase the total inositol phosphate levels of cultured tubules, as measured by ion exchange chromatography. Forskolin, a potent chloride secretagogue, has no effect on inositol phosphate formation. The uptake of 3 H-myo-inositol into phospholipids is very slow, preventing the detection of increased levels of inositol trisphosphate. However, significant increases in inositol monophosphate (IP1) and inositol biphosphate (IP2) were measured. The time course of VIP- and AP-stimulated IP1 and IP2 formation is similar to the effects of these agents on the short-circuit current responses of rectal gland monolayer cultures. In addition, aluminum fluoride, an artificial activator of guanine nucleotide-binding proteins, stimulates IP1 and IP2 formation. We conclude that rectal gland cells contain VIP and AP receptors coupled to the activation of phospholipase C. Coupling may be mediated by G-proteins. Receptor-stimulated increases in inositol phospholipid metabolism is one mechanism leading to increased intracellular free calcium concentrations, an important regulatory event in the activation of transepithelial chloride secretion by shark rectal gland epithelial cells

  15. Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation

    NARCIS (Netherlands)

    Michel, M. C.; Hanft, G.; Gross, G.

    1990-01-01

    We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol

  16. Gas Chromatographic Mass Spectrometric Determination of Myo-inositol in Humans Utilizing a Deuterated Internal Standard

    DEFF Research Database (Denmark)

    Andersen, Jan Rud; Larsen, Elfinn; Harbo, Helge

    1982-01-01

    The isotopic dilution technique was used for determining the content of myo-inositol in human urine, plasma and haemolysed erythrocyte samples. A deuterated myo-inositol, synthesized from inosose-2 by base-catalysed exchange of hydrogens by deuterium, followed by reduction of the inosose with 2H2...

  17. Dictyostelium discoideum contains three inositol monophosphatase activities with different substrate specificities and sensitivities to lithium

    NARCIS (Netherlands)

    Dijken, Peter van; Bergsma, Jan C.T.; Hiemstra, Hoebert S.; Vries, Berber de; Kaay, Jeroen van der; Haastert, Peter J.M. van

    1996-01-01

    The small ion lithium, a very effective agent in the treatment of manic depressive patients, inhibits the mammalian enzyme inositol monophosphatase, which is proposed as the biological target for the effects of lithium. In this study we investigated Dictyostelium discoideum inositol monophosphatase

  18. Retinoic acid treatment of fibroblasts causes a rapid Decrease in [3H]inositol uptake

    International Nuclear Information System (INIS)

    Sinha, R.; Creek, K.E.; Silverman-Jones, C.; de Luca, L.M.

    1989-01-01

    NIH 3T3 fibroblasts treated with all-trans-retinoic acid (RA) showed a dramatic decrease in the uptake of [ 3 H]inositol compared to solvent-treated controls. The onset of RA-induced inhibition of [ 3 H]inositol uptake was rapid with a 10-15% decrease occurring after 2-3 h of RA exposure and 60-70% reduction after 16 h of RA treatment. A progressive dose-dependent decrease in inositol uptake was found as the concentration of RA increased from 10 -8 to 10 -5 M and the effect was fully reversible within 48 h after RA removal. RA inhibition of inositol uptake was also observed in 3T3-Swiss and Balb/3T3 cells but not in two virally transformed 3T3 cell lines. Phlorizin, amiloride, and monensin inhibited inositol uptake by 66, 74, and 58%, respectively, and this inhibition was additive when the cells were treated with RA as well as these inhibitors. A decreased incorporation of [ 3 H]inositol into polyphosphoinositides was also observed in RA-treated cells but not to the same extent as for [ 3 H]inositol uptake. In conclusion, RA treatment of 3T3 fibroblasts decreases the uptake of [ 3 H]inositol by up to 70% within 8 to 10 h at near physiological concentrations in a reversible and specific manner

  19. Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement.

    Science.gov (United States)

    Dinicola, Simona; Fabrizi, Gianmarco; Masiello, Maria Grazia; Proietti, Sara; Palombo, Alessandro; Minini, Mirko; Harrath, Abdel Halim; Alwasel, Saleh H; Ricci, Giulia; Catizone, Angela; Cucina, Alessandra; Bizzarri, Mariano

    2016-07-01

    Inositol displays multi-targeted effects on many biochemical pathways involved in epithelial-mesenchymal transition (EMT). As Akt activation is inhibited by inositol, we investigated if such effect could hamper EMT in MDA-MB-231 breast cancer cells. In cancer cells treated with pharmacological doses of inositol E-cadherin was increased, β-catenin was redistributed behind cell membrane, and metalloproteinase-9 was significantly reduced, while motility and invading capacity were severely inhibited. Those changes were associated with a significant down-regulation of PI3K/Akt activity, leading to a decrease in downstream signaling effectors: NF-kB, COX-2, and SNAI1. Inositol-mediated inhibition of PS1 leads to lowered Notch 1 release, thus contributing in decreasing SNAI1 levels. Overall, these data indicated that inositol inhibits the principal molecular pathway supporting EMT. Similar results were obtained in ZR-75, a highly metastatic breast cancer line. These findings are coupled with significant changes on cytoskeleton. Inositol slowed-down vimentin expression in cells placed behind the wound-healing edge and stabilized cortical F-actin. Moreover, lamellipodia and filopodia, two specific membrane extensions enabling cell migration and invasiveness, were no longer detectable after inositol addiction. Additionally, fascin and cofilin, two mandatory required components for F-actin assembling within cell protrusions, were highly reduced. These data suggest that inositol may induce an EMT reversion in breast cancer cells, suppressing motility and invasiveness through cytoskeleton modifications. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Up-regulation of phosphoinositide metabolism in tobacco cells constitutively expressing the human type I inositol polyphosphate 5-phosphatase

    Science.gov (United States)

    Perera, Imara Y.; Love, John; Heilmann, Ingo; Thompson, William F.; Boss, Wendy F.; Brown, C. S. (Principal Investigator)

    2002-01-01

    To evaluate the impact of suppressing inositol 1,4,5-trisphosphate (InsP(3)) in plants, tobacco (Nicotiana tabacum) cells were transformed with the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme which specifically hydrolyzes InsP(3). The transgenic cell lines showed a 12- to 25-fold increase in InsP 5-ptase activity in vitro and a 60% to 80% reduction in basal InsP(3) compared with wild-type cells. Stimulation with Mas-7, a synthetic analog of the wasp venom peptide mastoparan, resulted in an approximately 2-fold increase in InsP(3) in both wild-type and transgenic cells. However, even with stimulation, InsP(3) levels in the transgenic cells did not reach wild-type basal values, suggesting that InsP(3) signaling is compromised. Analysis of whole-cell lipids indicated that phosphatidylinositol 4,5-bisphosphate (PtdInsP(2)), the lipid precursor of InsP(3), was greatly reduced in the transgenic cells. In vitro assays of enzymes involved in PtdInsP(2) metabolism showed that the activity of the PtdInsP(2)-hydrolyzing enzyme phospholipase C was not significantly altered in the transgenic cells. In contrast, the activity of the plasma membrane PtdInsP 5 kinase was increased by approximately 3-fold in the transgenic cells. In vivo labeling studies revealed a greater incorporation of (32)P into PtdInsP(2) in the transgenic cells compared with the wild type, indicating that the rate of PtdInsP(2) synthesis was increased. These studies show that the constitutive expression of the human type I InsP 5-ptase in tobacco cells leads to an up-regulation of the phosphoinositide pathway and highlight the importance of PtdInsP(2) synthesis as a regulatory step in this system.

  1. Bone turnover in postmenopausal osteoporosis

    International Nuclear Information System (INIS)

    Thomsen, K.

    1988-02-01

    Studies of the bone turnover in postmenopausal osteoporosis are essential, because the associated bone loss is inevitably due to the relative increase of bone resorption compared with bone formation. Measurement of the bone mineral content (BMC) in normal adults is assessed - partly on the uncorrected values and partly in proportion to the body muscle mass. The whole body retention (WBR) method is presented. The WBR and alternative urinary excretion (UE) methods used by the author are characterised and compared with the retention methods described in the literature. The representativity of WBR and UE for the estimation of bone turnover in normal subjects and patients with various bone metabolic diseases is discussed. The conclusion is that the modified retention methods used by the author have a satisfactory precision and accuracy in relation to the clinical studies carried out. The author's modification of the WBR method for determination of bone turnover and the alternative urinary excretion method (UE) consists in continuous scanning in the whole body count, using a gamma camera, and with the collimator a short distance from the volunteer. This procedure has the advantage of restricting the radioactive dose to 2 mCi (72 MBa). This is smaller by a factor of 5-10 than the dose used to measure WBR with equally simple counting equipment: With the author's procedure, using frontal counting, WBR is systematically underestimated by about 4 per cent point compared to the purely dorsal count, but since the frontal position is the most comfortable, requires a smaller radioactive dose, and the error is systematic, it is the preferred counting procedure. Correction of WBR and UE for bone mineral content is in principle a new parameter of bone turnover, whose improved accuracy increases the validity of the retention determinations. 136 refs. (EG)

  2. Partial genetic turnover in Neandertals

    DEFF Research Database (Denmark)

    Dalén, Love; Orlando, Ludovic Antoine Alexandre; Shapiro, Beth

    2012-01-01

    that recent western European neandertals (48 kyr) European neandertals. Using control region sequences, Bayesian demographic simulations provide higher support for a model of population fragmentation followed by separate demographic trajectories in subpopulations over a null model of a single stable...... population. The most parsimonious explanation for these results is that of a population turnover in western Europe during early Marine Isotope Stage 3, predating the arrival of anatomically modern humans in the region....

  3. Analysis and control of employee turnover.

    Science.gov (United States)

    McConnell, Charles R

    2007-01-01

    Turnover is a relatively simple and easily described concept. However, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect, and thus, not readily visible. There are a variety of causes of turnover, some which can be corrected and some which cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role.

  4. Supervisory turnover in outpatient substance abuse treatment.

    Science.gov (United States)

    Knight, Danica K; Broome, Kirk M; Edwards, Jennifer R; Flynn, Patrick M

    2011-01-01

    Staff turnover is a significant issue within substance abuse treatment, with implications for service delivery and organizational health. This study examined factors associated with turnover among supervisors in outpatient substance abuse treatment. Turnover was conceptualized as being an individual response to organizational-level influences, and predictors represent aggregate program measures. Participants included 532 staff (including 467 counselors and 65 clinical/program directors) from 90 programs in four regions of the USA. Using logistic regression, analyses of structural factors indicated that programs affiliated with a parent organization and those providing more counseling hours to clients had higher turnover rates. When measures of job attitudes were included, only parent affiliation and collective appraisal of satisfaction were related to turnover. Subsequent analyses identified a trend toward increased supervisory turnover when satisfaction was low following the departure of a previous supervisor. These findings suggest that organizational-level factors can be influential in supervisory turnover.

  5. Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth.

    Science.gov (United States)

    González-Salgado, Amaia; Steinmann, Michael; Major, Louise L; Sigel, Erwin; Reymond, Jean-Louis; Smith, Terry K; Bütikofer, Peter

    2015-06-01

    myo-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized de novo from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na(+)- or H(+)-linked myo-inositol transporters. While Na(+)-coupled myo-inositol transporters are found exclusively in the plasma membrane, H(+)-linked myo-inositol transporters are detected in intracellular organelles. In Trypanosoma brucei, the causative agent of human African sleeping sickness, myo-inositol metabolism is compartmentalized. De novo-synthesized myo-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the myo-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi complex. We now provide evidence that the Golgi complex-localized T. brucei H(+)-linked myo-inositol transporter (TbHMIT) is essential in bloodstream-form T. brucei. Downregulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for myo-inositol. It tolerates only a single modification on the inositol ring, such as the removal of a hydroxyl group or the inversion of stereochemistry at a single hydroxyl group relative to myo-inositol. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Insights into the activation mechanism of class I HDAC complexes by inositol phosphates

    Science.gov (United States)

    Watson, Peter J.; Millard, Christopher J.; Riley, Andrew M.; Robertson, Naomi S.; Wright, Lyndsey C.; Godage, Himali Y.; Cowley, Shaun M.; Jamieson, Andrew G.; Potter, Barry V. L.; Schwabe, John W. R.

    2016-01-01

    Histone deacetylases (HDACs) 1, 2 and 3 form the catalytic subunit of several large transcriptional repression complexes. Unexpectedly, the enzymatic activity of HDACs in these complexes has been shown to be regulated by inositol phosphates, which bind in a pocket sandwiched between the HDAC and co-repressor proteins. However, the actual mechanism of activation remains poorly understood. Here we have elucidated the stereochemical requirements for binding and activation by inositol phosphates, demonstrating that activation requires three adjacent phosphate groups and that other positions on the inositol ring can tolerate bulky substituents. We also demonstrate that there is allosteric communication between the inositol-binding site and the active site. The crystal structure of the HDAC1:MTA1 complex bound to a novel peptide-based inhibitor and to inositol hexaphosphate suggests a molecular basis of substrate recognition, and an entropically driven allosteric mechanism of activation. PMID:27109927

  7. Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5-phosphatase

    NARCIS (Netherlands)

    Dijken, Peter van; Lammers, Aleida A.; Ozaki, Shoichiro; Potter, Barry V.L.; Erneux, Christophe; Haastert, Peter J.M. van

    1994-01-01

    A series of P-32-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P-4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] analogues using recombinant rat brain Ins(1,4,5)P-3 3-kinase and [gamma-P-32]ATP. Ins(1,4,5)P-3 analogues

  8. myo-Inositol and d-Ribose Ligand Discrimination in an ABC Periplasmic Binding Protein

    Science.gov (United States)

    Herrou, Julien

    2013-01-01

    The periplasmic binding protein (PBP) IbpA mediates the uptake of myo-inositol by the IatP-IatA ATP-binding cassette transmembrane transporter. We report a crystal structure of Caulobacter crescentus IbpA bound to myo-inositol at 1.45 Å resolution. This constitutes the first structure of a PBP bound to inositol. IbpA adopts a type I PBP fold consisting of two α-β lobes that surround a central hinge. A pocket positioned between the lobes contains the myo-inositol ligand, which binds with submicromolar affinity (0.76 ± 0.08 μM). IbpA is homologous to ribose-binding proteins and binds d-ribose with low affinity (50.8 ± 3.4 μM). On the basis of IbpA and ribose-binding protein structures, we have designed variants of IbpA with inverted binding specificity for myo-inositol and d-ribose. Five mutations in the ligand-binding pocket are sufficient to increase the affinity of IbpA for d-ribose by 10-fold while completely abolishing binding to myo-inositol. Replacement of ibpA with these mutant alleles unable to bind myo-inositol abolishes C. crescentus growth in medium containing myo-inositol as the sole carbon source. Neither deletion of ibpA nor replacement of ibpA with the high-affinity ribose binding allele affected C. crescentus growth on d-ribose as a carbon source, providing evidence that the IatP-IatA transporter is specific for myo-inositol. This study outlines the evolutionary relationship between ribose- and inositol-binding proteins and provides insight into the molecular basis upon which these two related, but functionally distinct, classes of periplasmic proteins specifically bind carbohydrate ligands. PMID:23504019

  9. Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer

    International Nuclear Information System (INIS)

    Kaur, Jatinder; Sawhney, Meenakshi; DattaGupta, Siddartha; Shukla, Nootan K; Srivastava, Anurag; Ralhan, Ranju

    2010-01-01

    We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure. Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems. Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels. Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco

  10. Myo-inositol and melatonin in the menopausal transition.

    Science.gov (United States)

    D'Anna, Rosario; Santamaria, Angelo; Giorgianni, Grazia; Vaiarelli, Alberto; Gullo, Giuseppe; Di Bari, Flavia; Benvenga, Salvatore

    2017-04-01

    The aim of the study was to evaluate the effects on serum insulin and serum thyroid profile of a dietary supplement, myo-inositol, given alone or in combination with melatonin to women during menopausal transition. Forty women aged 45-55 years and at least 6 months of amenorrhea were enrolled in this study. They were randomly assigned to two groups of 20 each. One group took myo-inositol (myo-Ins) (2 g twice a day) and the other group took 2 g/d myo-Ins plus 3 g/d melatonin before sleeping. At the beginning of the study and after 6 months, all women were evaluated for the following indices: waist circumference, body mass index, blood pressure, endometrial thickness, as well as serum concentrations of TSH, FT3, FT4 and insulin. Both at baseline and at 6 months, the two groups were statistically similar for each of the considered indices. If percent changes (Δ%, 6 months over baseline) are contrasted in the two groups, serum TSH decreased in the myo-Ins group but increased in the latter, while serum insulin decreased in both groups. The combination of myo-Ins plus melatonin seems to affect positively glucose metabolism, while myo-Ins only seems to improve thyroid function.

  11. Regulation of endoplasmic reticulum turnover by selective autophagy.

    Science.gov (United States)

    Khaminets, Aliaksandr; Heinrich, Theresa; Mari, Muriel; Grumati, Paolo; Huebner, Antje K; Akutsu, Masato; Liebmann, Lutz; Stolz, Alexandra; Nietzsche, Sandor; Koch, Nicole; Mauthe, Mario; Katona, Istvan; Qualmann, Britta; Weis, Joachim; Reggiori, Fulvio; Kurth, Ingo; Hübner, Christian A; Dikic, Ivan

    2015-06-18

    The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process. However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.

  12. KECENDERUNGAN KEPUASAN KERJA SEBAGAI TRIGGER TURNOVER

    Directory of Open Access Journals (Sweden)

    Raditya Adi Saputra

    2017-06-01

    Full Text Available The purpose of this study are: (1 To determine the effect of job satisfaction on turnover intention; (2 To determine the effect of work stress on turnover intention; (3 To determine the effect of compensation on turnover intention; (4 To determine the effect of organizational climate on turnover intention; and (5 To determine the stress of work, compensation, organizational climate and job satisfaction effect on turnover intention. The population in this study are employees of the Cooperative KOKAPURA AVIA totaling 180 people, while employees who have worked more than three years as many as 128 people. Samples were taken 97 people. The technique of collecting data using questionnaires. The analysis used is multiple regression analysis and path analysis using PLS 3.0 Smart program. Based on the results of the study concluded that: (1 Job satisfaction significantly influence employee turnover intention; (2 Work stress significantly influence employee turnover intention; (3 Compensation incentives significantly influence employee turnover intention; (4 organizational climate significantly influence employee turnover intention; and (5 Work stress, incentive compensation, organizational climate and job satisfaction simultaneously significantly influence employee turnover intention.

  13. Tritium turnover in succulent plants

    International Nuclear Information System (INIS)

    Krishnamoorthy, T.M.; Gogate, S.S.; Soman, S.D.

    1977-01-01

    Measurements of turnover rates for tissue free water tritium (TFWT) and tissue bound tritium (TBT) were carried out in three succulent plants, Opuntia sp., E. Trigona and E. Mili using tritiated water as tracer. The estimated half-times were 52, 57.5 and 80 days for TFWT and 212, 318 and 132 days for TBT in the stems of the above plants respectively. Opuntia sp. showed significant incorporation of TBT, 10% of TFWT on weight basis, while the other two plants showed lesser incorporation, 2-3% of TFWT. However, the leaves of E. Mili indicated the same level of fixation of TBT as the stem of Opuntia sp. (author)

  14. Manager's guide to reducing dental hygiene turnover.

    Science.gov (United States)

    Loiacono, C

    1989-09-01

    The purpose of this paper is to address the issue of dental hygiene turnover and provide managers with strategies for preventing and reducing turnover. Employee turnover is a problem which affects dental health care delivery and the health of the public. Employee turnover is costly to work settings and creates a stressful working environment which has an impact on professional-client relationships. To reduce or prevent turnover in a private practice setting, office managers must be informed about the causes and effects of this problem and be able to implement solutions. Some strategies managers can use to reduce turnover are hiring employees who have the same goals as the organization; improving the working climate; rewarding longevity; encouraging the active participation of all staff members in office management; improving office communication; and providing opportunities for self-growth, recognition, and greater responsibilities.

  15. Rapid formation of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate.

    OpenAIRE

    Hawkins, P T; Stephens, L; Downes, C P

    1986-01-01

    Addition of 1 mM-carbachol to [3H]inositol-labelled rat parotid slices stimulated rapid formation of [3H]inositol 1,3,4,5-tetrakisphosphate, the accumulation of which reached a peak 20 s after stimulation, and then declined rapidly towards a new steady state. The initial rate of formation of inositol 1,3,4,5-tetrakisphosphate was slower than that for inositol 1,4,5-trisphosphate. The radioactivity in [3H]inositol 1,3,4,5-tetrakisphosphate fell quickly in carbachol-stimulated and then atropine...

  16. A double-blind, placebo-controlled study of inositol in trichotillomania.

    Science.gov (United States)

    Leppink, Eric W; Redden, Sarah A; Grant, Jon E

    2017-03-01

    Trichotillomania is characterized by repetitive pulling that causes noticeable hair loss. Data on the pharmacological treatment of trichotillomania are limited, with no clear first-line agent. The aim of the current study was to determine the efficacy and tolerability of inositol in adults with trichotillomania. A total of 38 individuals (35 women; mean age: 28.9±11.4) with trichotillomania entered a 10-week, double-blind, placebo-controlled trial to evaluate the safety and efficacy of inositol (dosing ranging from 6 to 18 g/day). Patients were assessed using the Massachusetts General Hospital Hair Pulling Scale, the NIMH Trichotillomania Severity Scale, Clinical Global Impression Scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using a linear mixed-effects model. Patients assigned to inositol failed to show significantly greater reductions on primary or secondary outcomes measures compared with placebo (all P>0.05). At study endpoint, 42.1% of patients were 'much or very much improved' on inositol compared with 35.3% on placebo. This is the first study assessing the efficacy of inositol in the treatment of trichotillomania, but found no differences in symptom reductions between inositol and placebo. Future studies should examine whether inositol may be beneficial in controlling pulling behavior in a subgroup of individuals with trichotillomania.

  17. Changes in inositol phosphates in wild carrot cells upon initiation of cell wall digestion

    International Nuclear Information System (INIS)

    Rincon, M.; Boss, W.F.

    1987-01-01

    Previous studies have shown that inositol trisphosphate (IP 3 ) stimulated 45 Ca +2 efflux from fusogenic carrot protoplasts and it was suggested that IP 3 may serve as a second messenger for the mobilization of intracellular Ca +2 in higher plant cells. To determine whether or not inositol phosphate metabolism changes in response to external stimuli, the cells were labeled with myo-[2- 3 H] inositol for 18 h and exposed to cell wall digestion enzymes, Driselase. The inositol phosphates were extracted with ice cold 10% TCA and separated by anion exchange chromatography. The radioactivity of the fraction that contained IP 3 increased 2-3.8 fold and that which contained inositol bisphosphate increased 1.9-2.6 fold within 1.5 min of exposure to Driselase. After 6 min, the radioactivity of both fractions increased 6-7.7 fold and an increase in inositol monophosphate was observed. These data indicate that inositol phosphate metabolism is stimulated by Driselase and suggest polyphosphoinositide hydrolysis occurs upon initiation of cell wall digestion

  18. Supervisory Turnover in Outpatient Substance Abuse Treatment

    OpenAIRE

    Knight, Danica K.; Broome, Kirk M.; Edwards, Jennifer R.; Flynn, Patrick M.

    2009-01-01

    Staff turnover is a significant issue within substance abuse treatment, with implications for service delivery and organizational health. This study examined factors associated with turnover among supervisors in outpatient substance abuse treatment. Turnover was conceptualized as being an individual response to organizational-level influences, and predictors represent aggregate program measures. Participants included 532 staff (including 467 counselors and 65 clinical/program directors) from ...

  19. Trade and Turnover: Theory and Evidence

    OpenAIRE

    Carl Davidson; Steven Matusz

    2005-01-01

    Is the pattern of trade correlated with cross-sector differences in job turnover? Theoretically, external shocks feed through to changes in domestic employment and cross-sector differences in turnover give rise to compensating wage differentials, which feed through to output prices. Using two different data sets on turnover, we find strong evidence that normalized US net exports by sector are negatively correlated with job destruction and worker separation rates. Weaker evidence suggests a po...

  20. Optimal Employee Turnover Rate: Theory and Evidence

    OpenAIRE

    Mark N. Harris; Kam-Ki Tang; Yi-Ping Tseng

    2002-01-01

    This paper investigates the quantitative effects of employee turnover on firms’ productivity. The Australian Business Longitudinal Survey 1995-98, a unique survey providing firm level data on both production and employee turnover, is used as the data source. Theoretical studies have advocated that firm specific human capital and job matching to be the two major, but competing, mechanisms through which turnover affects productivity. Our results indicate that the effect of job matching dominate...

  1. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    Science.gov (United States)

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  2. Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

    Science.gov (United States)

    Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

    2016-03-28

    Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

  3. Lipid Profile

    Science.gov (United States)

    ... Known As Coronary Risk Panel Formal Name Lipid Profile This article was last reviewed on June 29, ... phospholipid molecules. The particles measured with a lipid profile are classified by their density into high-density ...

  4. [New nurse turnover intention and influencing factors].

    Science.gov (United States)

    Han, Sang Sook; Sohn, In Soon; Kim, Nam Eun

    2009-12-01

    The study was done to identify turnover intention in new nurses according to characteristics of the nurses and other factors affecting turnover and to provide data to set up a strategy to reduce the turnover. Data were collected from 1,077 new nurses who had less than 12 months employment experience and worked in one of 188 hospitals. Eight research instruments were used. Data analysis was done using SPSS WIN 15.0 program. Several factors influence new nurse turnover intention. The average score for turnover intention was 2.12. The scores for subscales were self efficacy, 3.76, nursing performance, 3.90, job satisfaction, 2.09, organization commitment, 1.28, stress, 1.32, burnout, 2.82 and nursing organizational culture, 3.29. Turnover intention was related to self efficacy, nursing performance, job satisfaction, organization commitment, stress, burnout, nursing organizational culture, duration of in-class training, duration of on the job training, number of hospital beds, length of employment and duration of employment in current workplace. The predicting factors for turnover intention were burnout, stress, duration of employment in the current workplace, self efficacy and nursing performance. Those factors explained 51.6% of turnover intention. New nurse turnover intention can be reduced by mitigating the factors affecting this intention.

  5. Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling.

    Science.gov (United States)

    Shears, Stephen B

    2018-03-01

    Inositol pyrophosphates are small, diffusible signaling molecules that possess the most concentrated three-dimensional array of phosphate groups in Nature; up to eight phosphates are crammed around a six-carbon inositol ring. This review discusses the physico-chemical properties of these unique molecules, and their mechanisms of action. Also provided is information on the enzymes that regulate the levels and hence the signaling properties of these molecules. This review pursues the idea that many of the biological effects of inositol pyrophosphates can be rationalized by their actions at the interface of cell signaling and metabolism that is essential to cellular and organismal homeostasis. © 2017 Wiley Periodicals, Inc.

  6. Effects of epinephrine on ADP-induced changes in platelet inositol phosphates

    International Nuclear Information System (INIS)

    Vickers, J.D.; Keraly, C.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-01-01

    Epinephrine (EPI) does not aggregate rabbit platelets, but it does increase the labelling of inositol phosphate (IP) at 60s (21%, p + , in platelets prelabelled with [ 3 H] inositol. In contrast, 0.5 μM ADP which causes aggregation, increases the labelling of inositol bisphosphate (IP 2 ) by 30% (p 2 by 154% (p 2 stimulated by ADP + EPI was greater than the increase caused by ADP (p 2 due to 0.2 μM ADP + 0.6 μM EPI by 70% (p 2 by 108% (0 2 metabolism stimulated via the α-adrenergic receptor

  7. Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome.

    Science.gov (United States)

    Pacchiarotti, Alessandro; Carlomagno, Gianfranco; Antonini, Gabriele; Pacchiarotti, Arianna

    2016-01-01

    Polycystic ovarian syndrome (PCOS) induces anovulation in women of reproductive age, and is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Indeed, PCOS women are characterized by poor quality oocytes. Therefore, a treatment for enhancing oocyte quality becomes crucial for these patients. Myo-Inositol and melatonin proved to be efficient predictors for positive IVF outcomes, correlating with high oocyte quality. We tested the synergistic effect of myo-inositol and melatonin in IVF protocols with PCOS patients in a randomized, controlled, double-blind trial. Five-hundred twenty-six PCOS women were divided into three groups: Controls (only folic acid: 400 mcg), Group A (Inofolic® plus, a daily dose of myo-inositol: 4000 mg, folic acid: 400 mcg, and melatonin: 3 mg), and Group B (Inofolic®, a daily dose of myo-inositol: 4000 mg, and folic acid: 400 mcg). The main outcome measures were oocyte and embryo quality, clinical pregnancy and implantation rates. The treatment lasted from the first day of the cycle until 14 days after embryo transfer. Myo-inositol and melatonin have shown to enhance, synergistically, oocyte and embryo quality. In consideration of the beneficial effect observed in our trial and on the bases of previous studies, we decided to integrate routinely MI and M supplementation in the IVF protocols. The same treatment should be taken carefully in consideration in all procedures of this kind.

  8. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    Science.gov (United States)

    Durmus, Ali Said; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Komorowski, James Richard; Ali, Shakir; Sahin, Kazim

    2017-05-01

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P < 0.05). The mean unhealed wound area was significantly smaller, and the mean percentage of total wound healing was significantly higher in ASI-treated wounds than in the control wounds. Hydroxyproline, collagen, and matrix metalloproteinases were measured in the granulated tissue and found to be affected. Inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), collagen, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  9. Exercise, training and red blood cell turnover.

    Science.gov (United States)

    Smith, J A

    1995-01-01

    Endurance training can lead to what has been termed 'sports anaemia'. Although under normal conditions, red blood cells (RBCs) have a lifespan of about 120 days, the rate of aging may increase during intensive training. However, RBC deficiency is rare in athletes, and sports anaemia is probably due to an expanded plasma volume. Cycling, running and swimming have been shown to cause RBC damage. While most investigators measure indices of haemolysis (for example, plasma haemoglobin or haptoglobin), RBC removal is normally an extravascular process that does not involve haemolysis. Attention is now turning to cellular indices (such as antioxidant depletion, or protein or lipid damage) that may be more indicative of exercise-induced damage. RBCs are vulnerable to oxidative damage because of their continuous exposure to oxygen and their high concentrations of polyunsaturated fatty acids and haem iron. As oxidative stress may be proportional to oxygen uptake, it is not surprising that antioxidants in muscle, liver and RBCs can be depleted during exercise. Oxidative damage to RBCs can also perturb ionic homeostasis and facilitate cellular dehydration. These changes impair RBC deformability which can, in turn, impede the passage of RBCs through the microcirculation. This may lead to hypoxia in working muscle during single episodes of exercise and possibly an increased rate of RBC destruction with long term exercise. Providing RBC destruction does not exceed the rate of RBC production, no detrimental effect to athletic performance should occur. An increased rate of RBC turnover may be advantageous because young cells are more efficient in transporting oxygen. Because most techniques examine the RBC population as a whole, more sophisticated methods which analyse cells individually are required to determine the mechanisms involved in exercise-induced damage of RBCs.

  10. Turnover, Biographical Data, and Fair Employment Practice

    Science.gov (United States)

    Cascio, Wayne F.

    1976-01-01

    Describes a study that tested the validity of using job applicants' biographical data to predict employee turnover among minority and nonminority female clerical personnel. Findings showed that even after satisfying legal requirements for using such information, turnover can be predicted quite accurately. For availability see EA 507 670.…

  11. Relationship between Job Satisfaction and Turnover Intention ...

    African Journals Online (AJOL)

    This study explores the association between job satisfaction and turnover intentions among lecturers in three public universities in Tanzania. It had three objectives: (1) to determine the level of perceived job satisfaction among lecturers; (2) to determine the association between job satisfaction and turnover intention; and (3) ...

  12. Employee Turnover: Evidence from a Case Study.

    Science.gov (United States)

    Borland, Jeff

    1997-01-01

    Patterns of employee turnover from a medium-sized law firm in Australia were examined in regard to theories of worker mobility (matching, sectoral shift, and incentive). Results support a role for matching effects, but personnel practices affect the timing of turnover. Matching and incentive-based theories do not explain the high rates of turnover…

  13. University Lecturers' Professional Empowerment and Turnover in ...

    African Journals Online (AJOL)

    Many universities in Uganda are grappling with the challenge of academic staff turnover. While research conducted so far has established different factors explaining the problems of turnover, many of which have been addressed, this challenge has not been resolved. Hitherto, attention has not been paid to whether ...

  14. Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations with Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Simona Dinicola

    2017-10-01

    Full Text Available Communities eating a western-like diet, rich in fat, sugar and significantly deprived of fibers, share a relevant increased risk of both metabolic and cancerous diseases. Even more remarkable is that a low-fiber diet lacks some key components—as phytates and inositols—for which a mechanistic link has been clearly established in the pathogenesis of both cancer and metabolic illness. Reduced bioavailability of inositol in living organisms could arise from reduced food supply or from metabolism deregulation. Inositol deregulation has been found in a number of conditions mechanistically and epidemiologically associated to high-glucose diets or altered glucose metabolism. Indeed, high glucose levels hinder inositol availability by increasing its degradation and by inhibiting both myo-Ins biosynthesis and absorption. These underappreciated mechanisms may likely account for acquired, metabolic deficiency in inositol bioavailability.

  15. Effect of exogenous phytase on degradation of inositol phosphate in dairy cows

    DEFF Research Database (Denmark)

    Brask-Pedersen, Dorte Buus; Glitsø, Lene Vibe; Skov, L.K.

    2013-01-01

    The effect of exogenous phytase on inositol phosphate degradation in the rumen of dairy cows was investigated in a 4 × 4 Latin square design. Four lactating Danish Holstein cows fitted with ruminal, duodenal, and ileal cannulas were offered a total mixed ration (TMR) with a high content of inositol......, and high phytase doses, respectively). It was not possible to distinguish between the degradation of inositol phosphate occurring in the TMR and in the rumen. Exogenous phytase had no effect on total P intake or flow of total P to the duodenum and ileum, whereas exogenous phytase increased flow...... of microbial P to the duodenum and total fecal P excretion. None of the investigated rumen variables (pH, degradability of neutral detergent fiber, and rumen kinetics for neutral detergent fiber) were affected by treatment. Rumen and total-tract degradations of inositol phosphate were increased when exogenous...

  16. Efficient Synthesis of a Conformationally Rigid Polymer Based on myo-Inositol Carbonate

    International Nuclear Information System (INIS)

    Lee, Hye Jin; Kim, Tae Hyun

    2006-01-01

    We have successfully synthesized the polystyrene carrying a conformationally rigid myo-inositol substituent as a possible metal-chelating ligand. We are further investigating the metal binding properties of this polymer and its applicability to the practical use such as molecular imprinting. Compounds having three syn-axial hydroxyl groups on a six membered ring draw an interest due to their ability to form complexes with many cations. The steric requirements of the cyclohexane polyols to form complexes with cations are, however, rather strict and only a few such compounds with three syn-axial hydroxyls, including cis-inositol, were known. Moreover, none of these compounds is readily available, especially in large scales. Recently, synthesis of the readily available myo-inositol 4,6-carbonate with three hydroxyl groups at the axial position on a cyclohexane was reported. To our knowledge, this was the first example of the conformationally rigid cyclohexane polyols using the readily available myo-inositol

  17. Permissive roles of phosphatidyl inositol-3-kinase and Akt in skeletal myocyte maturation

    Czech Academy of Sciences Publication Activity Database

    Wilson, E.M.; Turečková, Jolana; Rotwein, P.

    2004-01-01

    Roč. 15, č. 2 (2004), s. 497-505 ISSN 1059-1524 Keywords : phosphatidyl inositol 3-kinase * Akt * muscle differentiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.517, year: 2004

  18. Cyclic AMP-dependent phosphorylation of a brain inositol trisphosphate receptor decreases its release of calcium

    International Nuclear Information System (INIS)

    Supattapone, S.; Danoff, S.K.; Theibert, A.; Joseph, S.K.; Steiner, J.; Snyder, S.H.

    1988-01-01

    The authors report the stoichiometric phosphorylation of an inositol 1,4,5-trisphosphate receptor-binding protein from rat brain by the cAMP-dependent protein kinase but not by protein kinase C or Ca 2+ /calmodulin-dependent protein kinase. This phosphorylation event does not markedly alter [ 3 H]inositol 1,4,5-trisphosphate-binding characteristics. However, inositol 1,4,5-trisphosphate is only 10% as potent in releasing 45 Ca 2+ from phosphorylated, as compared with native, cerebellar microsomes. Phosphorylation of the inositol 1,4,5-trisphosphate-binding protein by the cAMP-dependent protein kinase may provide a biochemical substrate for second-messenger cross talk

  19. Predictors of turnover intention in nurse faculty.

    Science.gov (United States)

    Gormley, Denise K; Kennerly, Susan

    2011-04-01

    Turnover of nurse faculty is an increasingly important issue in nursing as the available number of qualified faculty continues to decrease. Understanding the factors that contribute to turnover is important to academic administrators to retain and recruit qualified nursing faculty. The purpose of this study was to examine predictors of turnover intention in nurse faculty working in departments and schools of nursing in Carnegie Doctoral/Research Universities-Extensive, public and private, not-for-profit institutions. The multidimensional model of organizational commitment was used to frame this study. The predictor variables explored were organizational climate, organizational commitment, work role balance, role ambiguity, and role conflict. The work roles examined were research, teaching, and service. Logistical regression was performed to examine the predictors of turnover intention. Organizational climate intimacy and disengagement, affective and continuance organizational commitment, and role ambiguity were shown to predict turnover intention in nurse faculty. Copyright 2011, SLACK Incorporated.

  20. Inositol polyphosphates contribute to cellular circadian rhythms: Implications for understanding lithium's molecular mechanism.

    Science.gov (United States)

    Wei, Heather; Landgraf, Dominic; Wang, George; McCarthy, Michael J

    2018-01-11

    Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP 6 ) has effects on circadian rhythms. Using a bioluminescent reporter (Per2::luc) to measure circadian rhythms, we determined that IP 6 increased rhythm amplitude and shortened period in NIH3T3 cells. The IP 6 effect on amplitude was attenuated by selective siRNA knockdown of GSK3B and pharmacological blockade of AKT kinase. However, unlike lithium, IP 6 did not induce serine-9 phosphorylation of GSK3B. The synthesis of IP 6 involves the enzymes inositol polyphosphate multikinase (IPMK) and inositol pentakisphosphate 2-kinase (IPPK). Knockdown of Ippk had effects opposite to those of IP 6 , decreasing rhythm amplitude and lengthening period. Ipmk knockdown had few effects on rhythm alone, but attenuated the effects of lithium on rhythms. However, lithium did not change the intracellular content of IP 6 in NIH3T3 cells or neurons. Pharmacological inhibition of the IP 6 kinases (IP6K) increased rhythm amplitude and shortened period, suggesting secondary effects of inositol pyrophosphates may underlie the period shortening effect, but not the amplitude increasing effect of IP 6 . Overall, we conclude that inositol phosphates, in particular IP 6 have effects on circadian rhythms. Manipulations affecting IP 6 and related inositol phosphates may offer a novel means through which circadian rhythms can be regulated. Published by Elsevier Inc.

  1. Enumeration of Klebsiella spp. in cold water by using MacConkey-inositol-potassium tellurite medium.

    OpenAIRE

    Dutka, B J; Jones, K; Bailey, H

    1987-01-01

    MacConkey-inositol-potassium tellurite agar was field tested for its ability to selectively enumerate Klebsiella species from the waters of the Saint John River Basin, which include fresh and marine waters. Water temperature varied from 1 to 6 degrees C during the survey period. Results of the study indicated that 77% of the typical colonies on MacConkey-inositol-potassium tellurite medium were Klebsiella species, but the total Klebsiella population enumerated was greatly underestimated.

  2. Enumeration of Klebsiella spp. in cold water by using MacConkey-inositol-potassium tellurite medium.

    Science.gov (United States)

    Dutka, B J; Jones, K; Bailey, H

    1987-07-01

    MacConkey-inositol-potassium tellurite agar was field tested for its ability to selectively enumerate Klebsiella species from the waters of the Saint John River Basin, which include fresh and marine waters. Water temperature varied from 1 to 6 degrees C during the survey period. Results of the study indicated that 77% of the typical colonies on MacConkey-inositol-potassium tellurite medium were Klebsiella species, but the total Klebsiella population enumerated was greatly underestimated.

  3. Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol

    International Nuclear Information System (INIS)

    Pugliese, G.; Tilton, R.G.; Speedy, A.; Santarelli, E.; Eades, D.M.; Province, M.A.; Kilo, C.; Sherman, W.R.; Williamson, J.R.

    1990-01-01

    To assess the potential of myo-inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, (1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, (2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, (3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and (4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo-inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats

  4. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial.

    Science.gov (United States)

    Farren, Maria; Daly, Niamh; McKeating, Aoife; Kinsley, Brendan; Turner, Michael J; Daly, Sean

    2017-06-01

    This study investigated if inositol in a combination of myo -inositol and D -chiro-inositol would prevent gestational diabetes mellitus (GDM) in women with a family history of diabetes. This was a randomized controlled trial that examined whether inositol from the first antenatal visit prevents GDM. The trial was carried out in a single-center tertiary referral center. Women with a family history of diabetes were enrolled at the first antenatal visit. They were randomized to the intervention group, which received a combination of 1,100 mg myo -inositol, 27.6 mg D -chiro-inositol, and 400 μg folic acid, or to the control group, which received 400 μg folic acid only. All women had an oral glucose tolerance test between 24 and 28 weeks' gestation. The primary end point was the incidence of GDM. Statistical analysis was carried out using SPSS Statistical Package version 20. Two hundred forty women, 120 in each arm, were recruited between January 2014 and July 2015. There were no differences in characteristics between the groups. The incidence of GDM was 23.3% ( n = 28) in the intervention group compared with 18.3% ( n = 22) in the control group ( P = 0.34). The mean fasting plasma glucose at the glucose tolerance test was 81 mg/dL in both groups. Commencing an inositol combination in early pregnancy did not prevent GDM in women with a family history of diabetes. Further studies are required to examine whether inositol supplements at varying doses may prevent GDM. © 2017 by the American Diabetes Association.

  5. Chronic Teacher Turnover in Urban Elementary Schools

    Directory of Open Access Journals (Sweden)

    Kacey Guin

    2004-08-01

    Full Text Available This study examines the characteristics of elementary schools that experience chronic teacher turnover and the impacts of turnover on a school’s working climate and ability to effectively function. Based on evidence from staff climate surveys and case studies, it is clear that high turnover schools face significant organizational challenges. Schools with high teacher turnover rates have difficulty planning and implementing a coherent curriculum and sustaining positive working relationships among teachers. The reality of these organizational challenges is particularly alarming, given that high turnover schools are more likely to serve low-income and minority students. The negative relationship between teacher turnover and school functioning, and the fact that turbulent schools are disproportionately likely to serve lowincome and minority students have important implications for both district and school-level policies. Specifically: Teacher turnover rates are one indicator of school health, which school districts should consider when focusing on school improvements. Districts need to begin by developing the means to identify individual schools that experience high levels of teacher turnover. Current district policies in implementing professional development for teachers in low-performing schools are inefficient when teachers do not remain in the schools in which they are trained. In order for low-performing schools to improve, districts need to consider providing incentive programs so that high quality teachers apply for, and remain in, these schools. Future research is needed to address the causal link between turnover, organizational functioning and student outcomes. Additionally, there is a need for research examining district policies that may facilitate teacher turnover within a district, including how districts place and transfer teachers, as well as how teachers’ salaries are budgeted.

  6. System turnover and acceptance procedure of Qingshan NPP

    International Nuclear Information System (INIS)

    Sun Guangdi; Wu Guanxin

    1993-01-01

    Turnover and acceptance process of nuclear power plant has direct influence on construction scheduling. The authors describe organization, conditions and implementation of system turnover and acceptance. The paper also gives some suggestions as reference of turnover and acceptance work

  7. Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

    Directory of Open Access Journals (Sweden)

    Felicia D’Andrea

    2016-11-01

    Full Text Available The intramolecular aldol condensation of aldohexos-5-ulose derivatives of the D-xylo and L-ribo stereoseries has been studied. Only one of the four possible inososes was isolated from both stereoseries in reasonable yields (30–38%. The results obtained, together with the previous findings for the L-arabino and L-lyxo stereoseries, allowed for the rationalisation of a mechanism of the reaction based on open-transition-state models and electron-withdrawing inductive effects. Complementary reductions of the intermediate inososes were possible by changing the reaction conditions, and two isomeric inositol derivatives were obtained with complete stereoselection from each inosose. The presented approach permits us to control the configuration of three out of the six stereocentres of the inositol frame and gives access to seven of the nine inositols. Noteworthy, for the D-xylo derivative, the two-step sequence (condensation followed by reduction with NaBH(OAc3 represents the biomimetic synthesis of myo-inositol. Furthermore, the sugar-based pathway leads directly to enantiomerically pure selectively protected inositols and does not require any desymmetrisation procedure which is needed when myo-inositol and other achiral precursors are employed as starting materials. As an example of application of the method, the indirect selective protection of secondary inositols’ hydroxy functions, by placing specific protecting groups on the aldohexos-5-ulose precursor has been presented.

  8. An in vitro synthetic biology platform for the industrial biomanufacturing of myo-inositol from starch.

    Science.gov (United States)

    You, Chun; Shi, Ting; Li, Yunjie; Han, Pingping; Zhou, Xigui; Zhang, Yi-Heng Percival

    2017-08-01

    Myo-Inositol (vitamin B8) is widely used in the drug, cosmetic, and food & feed industries. Here, we present an in vitro non-fermentative enzymatic pathway that converts starch to inositol in one vessel. This in vitro pathway is comprised of four enzymes that operate without ATP or NAD + supplementation. All enzyme BioBricks are carefully selected from hyperthermophilic microorganisms, that is, alpha-glucan phosphorylase from Thermotoga maritima, phosphoglucomutase from Thermococcus kodakarensis, inositol 1-phosphate synthase from Archaeoglobus fulgidus, and inositol monophosphatase from T. maritima. They were expressed efficiently in high-density fermentation of Escherichia coli BL21(DE3) and easily purified by heat treatment. The four-enzyme pathway supplemented with two other hyperthermophilic enzymes (i.e., 4-α-glucanotransferase from Thermococcus litoralis and isoamylase from Sulfolobus tokodaii) converts branched or linear starch to inositol, accomplishing a very high product yield of 98.9 ± 1.8% wt./wt. This in vitro (aeration-free) biomanufacturing has been successfully operated on 20,000-L reactors. Less costly inositol would be widely added in heath food, low-end soft drink, and animal feed, and may be converted to other value-added biochemicals (e.g., glucarate). This biochemical is the first product manufactured by the in vitro synthetic biology platform on an industrial scale. Biotechnol. Bioeng. 2017;114: 1855-1864. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Does myo-inositol effect on PCOS follicles involve cytoskeleton regulation?

    Science.gov (United States)

    Bizzarri, Mariano; Cucina, Alessandra; Dinicola, Simona; Harrath, Abdel Halim; Alwasel, Saleh H; Unfer, Vittorio; Bevilacqua, Arturo

    2016-06-01

    Inositol metabolism is severely impaired in follicles obtained from cystic ovaries, leading to deregulated insulin transduction and steroid synthesis. On the contrary, inositol administration to women suffering from polycystic ovary syndrome (PCOS) has been proven to efficiently counteract most of the clinical hallmarks displayed by PCOS patients, including insulin resistance, hyperandrogenism and oligo-amenorrhea. We have recently observed that myo-inositol induces significant changes in cytoskeletal architecture of breast cancer cells, by modulating different biochemical pathways, eventually modulating the epithelial-mesenchymal transition. We hypothesize that inositol and its monophosphate derivatives, besides their effects on insulin transduction, may efficiently revert histological and functional features of cystic ovary by inducing cytoskeleton rearrangements. We propose an experimental model that could address not only whether inositol modulates cytoskeleton dynamics in both normal and cystic ovary cells, but also whether this effect may interfere with ovarian steroidogenesis. A more compelling understanding of the mechanisms of action of inositol (and its derivatives) would greatly improve its therapeutic utilization, by conferring to current treatments a well-grounded scientific rationale. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Regioselective Opening of myo-Inositol Orthoesters: Mechanism and Synthetic Utility

    Science.gov (United States)

    2013-01-01

    Acid hydrolysis of myo-inositol 1,3,5-orthoesters, apart from orthoformates, exclusively affords the corresponding 2-O-acyl myo-inositol products via a 1,2-bridged five-membered ring dioxolanylium ion intermediate observed by NMR spectroscopy. These C-2-substituted inositol derivatives provide valuable precursors for rapid and highly efficient routes to 2-O-acyl inositol 1,3,4,5,6-pentakisphosphates and myo-inositol 1,3,4,5,6-pentakisphosphate with biologically interesting and anticancer properties. Deuterium incorporation into the α-methylene group of such alkyl ester products (2-O-C(O)CD2R), when the analogous alkyl orthoester is treated with deuterated acid, is established utilizing the novel orthoester myo-inositol 1,3,5-orthobutyrate as an example. Such deuterated ester products provide intermediates for deuterium-labeled synthetic analogues. Investigation into this selective formation of 2-O-ester products and the deuterium incorporation is presented with proposed mechanisms from NMR experiments. PMID:23438216

  11. Synthesis of inositol 1,2-(cyclic)-4,5-trisphosphate

    International Nuclear Information System (INIS)

    Auchus, R.J.; Kaiser, S.L.; Majerus, P.W.

    1987-01-01

    We have developed a method for synthesis of inositol 1,2-(cyclic)-4,5-trisphosphate from inositol 1,4,5-trisphosphate using a water-soluble carbodiimide. We obtained 1-1.5 mumol of the inositol cyclic trisphosphate starting with 5 mumol of inositol 1,4,5-trisphosphate. The cyclized product was isolated by HPLC on Partisil SAX. The identity of the cyclic product was verified by its hydrolysis to inositol 1,4,5-trisphosphate in acid and by its conversion to 1,2-(cyclic)-4-bisphosphate by a specific 5-phosphomonoesterase from platelets. We also identified the product by 31 P NMR spectroscopy, which showed a peak at 17.2 ppm, characteristic of a five-membered cyclic phosphodiester ring, and peaks at 4.1 ppm and 0.8 ppm, indicative of phosphomonoesters. This relatively simple method for producing inositol 1,2-(cyclic)-4,5-trisphosphate will facilitate studies of the physiology of this compound in signal transduction

  12. Inositol-phosphate signaling as mediator for growth and sexual reproduction in Podospora anserina.

    Science.gov (United States)

    Xie, Ning; Ruprich-Robert, Gwenaël; Chapeland-Leclerc, Florence; Coppin, Evelyne; Lalucque, Hervé; Brun, Sylvain; Debuchy, Robert; Silar, Philippe

    2017-09-01

    The molecular pathways involved in the development of multicellular fruiting bodies in fungi are still not well known. Especially, the interplay between the mycelium, the female tissues and the zygotic tissues of the fruiting bodies is poorly documented. Here, we describe PM154, a new strain of the model ascomycetes Podospora anserina able to mate with itself and that enabled the easy recovery of new mutants affected in fruiting body development. By complete genome sequencing of spod1, one of the new mutants, we identified an inositol phosphate polykinase gene as essential, especially for fruiting body development. A factor present in the wild type and diffusible in mutant hyphae was able to induce the development of the maternal tissues of the fruiting body in spod1, but failed to promote complete development of the zygotic ones. Addition of myo-inositol in the growth medium was able to increase the number of developing fruiting bodies in the wild type, but not in spod1. Overall, the data indicated that inositol and inositol polyphosphates were involved in promoting fruiting body maturation, but also in regulating the number of fruiting bodies that developed after fertilization. The same effect of inositol was seen in two other fungi, Sordaria macrospora and Chaetomium globosum. Key role of the inositol polyphosphate pathway during fruiting body maturation appears thus conserved during the evolution of Sordariales fungi. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Fast separation and determination of free myo-inositol by hydrophilic liquid chromatography.

    Science.gov (United States)

    Pazourek, Jiří

    2014-06-04

    A fast liquid chromatography method for separation and determination of myo-inositol is reported. Determination of the biologically important isomer of inositols, myo-inositol, was optimized to avoid overlapping to possible interferents according to European Pharmacopoeia (glycerol, d-mannitol) and saccharose. The method in HILIC mode is extremely selective to other carbohydrates which allows to separate myo-inositol from allo- and d-chiro-inositol with resolution 12.3 and 5.2, resp. and this way it enables to separate myo-inostiol from contingent carbohydrates present in a sample matrix. Retention time of myo-inositol was 12min at 10°C, though higher temperatures (25°C or 40°C) or higher water content in the mobile phase could speed up the separation and determination to four minutes. LOD of the method was 9mg/L at 10°C, and 5mg/L at 25°C, resp. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Etude du potentiel insulino-sensibilisant du myo-inositol chez la souris : Evaluation de l’intérêt nutritionnel d’une supplémentation en myo-inositol

    OpenAIRE

    Croze , Marine

    2013-01-01

    Insulin resistance is the first step in the development of type 2 diabetes so finding insulin-sensitizing strategies is challenging for scientists. Some inositol isomers or derivatives have been reported to exert insulin-mimetic activity. myo-Inositol being the most abundant stereoisomeric form of inositol in foodstuffs, we tested its insulin-mimetic potential in the long term and as a nutritional strategy for insulin resistance prevention and/or treatment. This study demonstrates that chroni...

  15. Turnover rates in microorganisms by laser ablation electrospray ionization mass spectrometry and pulse-chase analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stopka, Sylwia A.; Mansour, Tarek R.; Shrestha, Bindesh [Department of Chemistry, W.M. Keck Institute for Proteomics Technology and Applications, The George Washington University, Washington, DC 20052 (United States); Maréchal, Éric; Falconet, Denis [Laboratoire de Physiologie Cellulaire et Végétale, UMR 5168, CEA-CNRS-INRA-Univ. Grenoble Alpes, Grenoble (France); Vertes, Akos, E-mail: vertes@gwu.edu [Department of Chemistry, W.M. Keck Institute for Proteomics Technology and Applications, The George Washington University, Washington, DC 20052 (United States)

    2016-01-01

    Biochemical processes rely on elaborate networks containing thousands of compounds participating in thousands of reaction. Rapid turnover of diverse metabolites and lipids in an organism is an essential part of homeostasis. It affects energy production and storage, two important processes utilized in bioengineering. Conventional approaches to simultaneously quantify a large number of turnover rates in biological systems are currently not feasible. Here we show that pulse-chase analysis followed by laser ablation electrospray ionization mass spectrometry (LAESI-MS) enable the simultaneous and rapid determination of metabolic turnover rates. The incorporation of ion mobility separation (IMS) allowed an additional dimension of analysis, i.e., the detection and identification of isotopologs based on their collision cross sections. We demonstrated these capabilities by determining metabolite, lipid, and peptide turnover in the photosynthetic green algae, Chlamydomonas reinhardtii, in the presence of {sup 15}N-labeled ammonium chloride as the main nitrogen source. Following the reversal of isotope patterns in the chase phase by LAESI-IMS-MS revealed the turnover rates and half-lives for biochemical species with a wide range of natural concentrations, e.g., chlorophyll metabolites, lipids, and peptides. For example, the half-lives of lyso-DGTS(16:0) and DGTS(18:3/16:0), t{sub 1/2} = 43.6 ± 4.5 h and 47.6 ± 2.2 h, respectively, provided insight into lipid synthesis and degradation in this organism. Within the same experiment, half-lives for chlorophyll a, t{sub 1/2} = 24.1 ± 2.2 h, and a 2.8 kDa peptide, t{sub 1/2} = 10.4 ± 3.6 h, were also determined. - Highlights: • High-throughput pulse-chase analysis using direct sampling of biological cells. • Ion mobility separation for the elucidation of isotopologs. • Identification of isotopologs in difference heat plots of DT vs. m/z. • Simultaneous determination of turnover rates for lipids and

  16. Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling

    Science.gov (United States)

    Kinoshita, Taroh; Fujita, Morihisa

    2016-01-01

    Glycosylphosphatidylinositols (GPIs) act as membrane anchors of many eukaryotic cell surface proteins. GPIs in various organisms have a common backbone consisting of ethanolamine phosphate (EtNP), three mannoses (Mans), one non-N-acetylated glucosamine, and inositol phospholipid, whose structure is EtNP-6Manα-2Manα-6Manα-4GlNα-6myoinositol-P-lipid. The lipid part is either phosphatidylinositol of diacyl or 1-alkyl-2-acyl form, or inositol phosphoceramide. GPIs are attached to proteins via an amide bond between the C-terminal carboxyl group and an amino group of EtNP. Fatty chains of inositol phospholipids are inserted into the outer leaflet of the plasma membrane. More than 150 different human proteins are GPI anchored, whose functions include enzymes, adhesion molecules, receptors, protease inhibitors, transcytotic transporters, and complement regulators. GPI modification imparts proteins with unique characteristics, such as association with membrane microdomains or rafts, transient homodimerization, release from the membrane by cleavage in the GPI moiety, and apical sorting in polarized cells. GPI anchoring is essential for mammalian embryogenesis, development, neurogenesis, fertilization, and immune system. Mutations in genes involved in remodeling of the GPI lipid moiety cause human diseases characterized by neurological abnormalities. Yeast Saccharomyces cerevisiae has >60 GPI-anchored proteins (GPI-APs). GPI is essential for growth of yeast. In this review, we discuss biosynthesis of GPI-APs in mammalian cells and yeast with emphasis on the lipid moiety. PMID:26563290

  17. Inositol Pyrophosphate Profiling of Two HCT116 Cell Lines Uncovers Variation in InsP8 Levels.

    Directory of Open Access Journals (Sweden)

    Chunfang Gu

    Full Text Available The HCT116 cell line, which has a pseudo-diploid karotype, is a popular model in the fields of cancer cell biology, intestinal immunity, and inflammation. In the current study, we describe two batches of diverged HCT116 cells, which we designate as HCT116NIH and HCT116UCL. Using both gel electrophoresis and HPLC, we show that HCT116UCL cells contain 6-fold higher levels of InsP8 than HCT116NIH cells. This observation is significant because InsP8 is one of a group of molecules collectively known as 'inositol pyrophosphates' (PP-InsPs-highly 'energetic' and conserved regulators of cellular and organismal metabolism. Variability in the cellular levels of InsP8 within divergent HCT116 cell lines could have impacted the phenotypic data obtained in previous studies. This difference in InsP8 levels is more remarkable for being specific; levels of other inositol phosphates, and notably InsP6 and 5-InsP7, are very similar in both HCT116NIH and HCT116UCL lines. We also developed a new HPLC procedure to record 1-InsP7 levels directly (for the first time in any mammalian cell line; 1-InsP7 comprised <2% of total InsP7 in HCT116NIH and HCT116UCL lines. The elevated levels of InsP8 in the HCT116UCL lines were not due to an increase in expression of the PP-InsP kinases (IP6Ks and PPIP5Ks, nor to a decrease in the capacity to dephosphorylate InsP8. We discuss how the divergent PP-InsP profiles of the newly-designated HCT116NIH and HCT116UCL lines should be considered an important research opportunity: future studies using these two lines may uncover new features that regulate InsP8 turnover, and may also yield new directions for studying InsP8 function.

  18. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

  19. Empirical Prediction of Turnovers in NFL Football

    Directory of Open Access Journals (Sweden)

    Joel R. Bock

    2016-12-01

    Full Text Available Turnovers in the National Football League (NFL occur whenever a team loses possession of the ball due to a fumble, or an interception. Turnovers disrupt momentum of the offensive team, and represent lost opportunities to advance downfield and score. Teams with a positive differential turnover margin in a given game win 70 % of the time. Turnovers are statistically rare events, occurring apparently randomly. These characteristics make them difficult to predict. This investigation advances the hypothesis that turnovers are predictable in NFL football. Machine learning models are developed to learn the concept: At any point within a football game, what is the likelihood that a turnover will be observed on the next play from scrimmage? NFL play-by-play data for 32 teams spanning seven full seasons were used to train the models. Results presented suggest evidence to support the working hypothesis. Under certain conditions, both fumbles and interceptions can be anticipated at low false discovery rates (less than 15 % . When a turnover is predicted on the impending play from scrimmage, a high degree of confidence is associated with that prediction. The ability to anticipate catastrophic in-game events may lead to their management and control, ultimately improving the performance of individual athletes and their teams. This investigation contributes to the sports science literature by demonstrating the predictability of in-game events often considered to be essentially random in their occurrence. To the author’s knowledge, direct prediction of turnovers has not previously appeared in the literature, which has focused on retrospective statistical analyses of turnover margin in football games.

  20. Nurse turnover: a literature review - an update.

    Science.gov (United States)

    Hayes, Laureen J; O'Brien-Pallas, Linda; Duffield, Christine; Shamian, Judith; Buchan, James; Hughes, Frances; Laschinger, Heather K Spence; North, Nicola

    2012-07-01

    Concerns related to the complex issue of nursing turnover continue to challenge healthcare leaders in every sector of health care. Voluntary nurse turnover is shown to be influenced by a myriad of inter-related factors, and there is increasing evidence of its negative effects on nurses, patients and health care organizations. The objectives were to conduct a comprehensive review of the related literature to examine recent findings related to the issue of nursing turnover and its causes and consequences, and to identify on methodological challenges and the implications of new evidence for future studies. A comprehensive search of the recent literature related to nursing turnover was undertaken to summarize findings published in the past six years. Electronic databases: MEDLINE, CINAHL and PubMed, reference lists of journal publications. Keyword searches were conducted for publications published 2006 or later that examined turnover or turnover intention in employee populations of registered or practical/enrolled or assistant nurses working in the hospital, long-term or community care areas. Literature findings are presented using an integrative approach and a table format to report individual studies. From about 330 citations or abstracts that were initially scanned for content relevance, 68 studies were included in this summary review. The predominance of studies continues to focus on determinants of nurse turnover in acute care settings. Recent studies offer insight into generational factors that should be considered in strategies to promote stable staffing in healthcare organizations. Nursing turnover continues to present serious challenges at all levels of health care. Longitudinal research is needed to produce new evidence of the relationships between nurse turnover and related costs, and the impact on patients and the health care team. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Crystal Structure and Product Analysis of an Archaeal myo-Inositol Kinase Reveal Substrate Recognition Mode and 3-OH Phosphorylation.

    Science.gov (United States)

    Nagata, Ryuhei; Fujihashi, Masahiro; Sato, Takaaki; Atomi, Haruyuki; Miki, Kunio

    2015-06-09

    The TK2285 protein from Thermococcus kodakarensis was recently characterized as an enzyme catalyzing the phosphorylation of myo-inositol. Only two myo-inositol kinases have been identified so far, the TK2285 protein and Lpa3 from Zea mays, both of which belong to the ribokinase family. In either case, which of the six hydroxyl groups of myo-inositol is phosphorylated is still unknown. In addition, little is known about the myo-inositol binding mechanism of these enzymes. In this work, we determined two crystal structures: those of the TK2285 protein complexed with the substrates (ATP analogue and myo-inositol) or the reaction products formed by the enzyme. Analysis of the ternary substrates-complex structure and site-directed mutagenesis showed that five residues were involved in the interaction with myo-inositol. Structural comparison with other ribokinase family enzymes indicated that two of the five residues, Q136 and R140, are characteristic of myo-inositol kinase. The crystal structure of the ternary products-complex, which was prepared by incubating the TK2285 protein with myo-inositol and ATP, holds 1d-myo-inositol 3-phosphate (Ins(3)P) in the active site. NMR and HPLC analyses with a chiral column also indicated that the TK2285 reaction product was Ins(3)P. The results obtained here showed that the TK2285 protein specifically catalyzes the phosphorylation of the 3-OH of myo-inositol. We thus designated TK2285 as myo-inositol 3-kinase (MI3K). The precise identification of the reaction product should provide a sound basis to further explore inositol metabolism in Archaea.

  2. The validation of the turnover intention scale

    Directory of Open Access Journals (Sweden)

    Chris F.C. Bothma

    2013-04-01

    Full Text Available Orientation: Turnover intention as a construct has attracted increased research attention in the recent past, but there are seemingly not many valid and reliable scales around to measure turnover intention. Research purpose: This study focused on the validation of a shortened, six-item version of the turnover intention scale (TIS-6. Motivation for the study: The research question of whether the TIS-6 is a reliable and a valid scale for measuring turnover intention and for predicting actual turnover was addressed in this study. Research design, approach and method: The study was based on a census-based sample (n= 2429 of employees in an information, communication and technology (ICT sector company (N= 23 134 where the TIS-6 was used as one of the criterion variables. The leavers (those who left the company in this sample were compared with the stayers (those who remained in the employ of the company in this sample in respect of different variables used in the study. Main findings: It was established that the TIS-6 could measure turnover intentions reliably (α= 0.80. The TIS-6 could significantly distinguish between leavers and stayers (actual turnover, thereby confirming its criterion-predictive validity. The scale also established statistically significant differences between leavers and stayers in respect of a number of the remaining theoretical variables used in the study, thereby also confirming its differential validity. These comparisons were conducted for both the 4-month and the 4-year period after the survey was conducted. Practical/managerial implications: Turnover intention is related to a number of variables in the study which necessitates a reappraisal and a reconceptualisation of existing turnover intention models. Contribution/value-add: The TIS-6 can be used as a reliable and valid scale to assess turnover intentions and can therefore be used in research to validly and reliably assess turnover intentions or to

  3. AN ECONOMETRIC APPROACH ABOUT VOLUNTARY TURNOVER

    Directory of Open Access Journals (Sweden)

    ADALET EREN

    2013-06-01

    Full Text Available This study analyzes individual and organizational variables that affect voluntary turnover are determined in the special defence and security companies. A binomial logistic regression model is used to estimate voluntary turnover.  Binomial Logistic regression, reliability test (scale alfa, variance (ANOVA, Post-hoc/Tukey, correlation (Pearson and other basic statistical techniques  with SPSS 13 statistical packet program was used in the analyzes ofresearch data. The study finds that; situation of suppose working, number of child, number of death child, number of home’s moving, support of rent, total monthly income of household, last work’s region, number of prizes, affect voluntary turnover are determined.

  4. Improvements to Kramers turnover theory.

    Science.gov (United States)

    Pollak, Eli; Ankerhold, Joachim

    2013-04-28

    The Kramers turnover problem, that is, obtaining a uniform expression for the rate of escape of a particle over a barrier for any value of the external friction was solved in the 1980s. Two formulations were given, one by Mel'nikov and Meshkov (MM) [V. I. Mel'nikov and S. V. Meshkov, J. Chem. Phys. 85, 1018 (1986)], which was based on a perturbation expansion for the motion of the particle in the presence of friction. The other, by Pollak, Grabert, and Hänggi (PGH) [E. Pollak, H. Grabert, and P. Hänggi, J. Chem. Phys. 91, 4073 (1989)], valid also for memory friction, was based on a perturbation expansion for the motion along the collective unstable normal mode of the particle. Both theories did not take into account the temperature dependence of the average energy loss to the bath. Increasing the bath temperature will reduce the average energy loss. In this paper, we analyse this effect, using a novel perturbation theory. We find that within the MM approach, the thermal energy gained from the bath diverges, the average energy gain becomes infinite implying an essential failure of the theory. Within the PGH approach increasing the bath temperature reduces the average energy loss but only by a finite small amount of the order of the inverse of the reduced barrier height. Then, this does not seriously affect the theory. Analysis and application for a cubic potential and Ohmic friction are presented.

  5. Liquid Crystal Gel Reduces Age Spots by Promoting Skin Turnover

    Directory of Open Access Journals (Sweden)

    Mina Musashi

    2014-07-01

    Full Text Available Studies have shown that liquid crystals structurally resembling the intercellular lipids in the stratum corneum can beneficially affect the skin when applied topically by stimulating the skin’s natural regenerative functions and accelerating epidermal turnover. In the present study, the effects of applying low concentrations of a liquid crystal gel of our own creation were evaluated using epidermal thickening in mouse skin as an assay for effective stimulation of epidermal turnover. A liquid crystal gel was also applied topically to human facial skin, and analysis was conducted using before-and-after photographs of age spots, measurements of L* values that reflect degree of skin pigmentation, single-layer samples of the stratum corneum obtained via tape-stripping, and measurements of trans-epidermal water loss that reflect the status of the skin’s barrier function. The results suggested that cost-effective creams containing as low as 5% liquid crystal gel might be effective and safely sold as skin care products targeting age spots and other problems relating to uneven skin pigmentation.

  6. Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducing myo-inositol biosynthesis

    Science.gov (United States)

    Gardell, Alison M.; Yang, Jun; Sacchi, Romina; Fangue, Nann A.; Hammock, Bruce D.; Kültz, Dietmar

    2013-01-01

    SUMMARY This study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na+ and Cl− concentrations were also measured and significantly increased in response to both acute and chronic salinity challenges. Interestingly, highly significant positive correlations were found between MIB enzyme mRNA and blood plasma osmolality in both acute and chronic salinity acclimations. Additionally, a mass spectrometry assay was established and used to quantify total myo-inositol concentration in tilapia brain, which closely mirrored the hyperosmotic MIB pathway induction. Thus, myo-inositol is a major compatible osmolyte that is accumulated in brain cells when exposed to acute and chronic hyperosmotic challenge. These data show that the MIB pathway is highly induced in response to environmental salinity challenge in tilapia brain and that this induction is likely prompted by increases in blood plasma osmolality. Because the MIB pathway uses glucose-6-phosphate as a substrate and large amounts of myo-inositol are being synthesized, our data also illustrate that the MIB pathway likely contributes to the high energetic demand posed by salinity challenge. PMID:24072790

  7. The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol.

    Science.gov (United States)

    Chang, Hao-Han; Choong, Bernard; Phillips, Anthony R J; Loomes, Kerry M

    2015-01-01

    Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease. © 2014 by the Society for Experimental Biology and Medicine.

  8. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  9. Evaluation of Myo-Inositol as a Potential Biomarker for Depression in Schizophrenia.

    Science.gov (United States)

    Chiappelli, Joshua; Rowland, Laura M; Wijtenburg, S Andrea; Muellerklein, Florian; Tagamets, Malle; McMahon, Robert P; Gaston, Frank; Kochunov, Peter; Hong, L Elliot

    2015-08-01

    Depression is highly prevalent in patients with schizophrenia and is associated with significant clinical consequences, but there is no known biomarker for depression in schizophrenia. One of the putative neurochemical biomarkers for depression in major depressive disorder (MDD) is reduced cerebral concentration of myo-Inositol. We examined whether myo-Inositol levels provide a potential marker for depressive symptoms in schizophrenia similar to that in MDD and are informative regarding causal biological pathways underlying both depression and schizophrenia. We used proton magnetic resonance spectroscopy to examine myo-Inositol levels in the anterior cingulate cortex (ACC) in 59 schizophrenia spectrum disorder (SSD) patients and 69 matched community comparison participants. Participants completed the Maryland Trait and State Depression (MTSD) scale to measure symptoms of depression experienced around time of assessment ('State' subscale) and longitudinally ('Trait' subscale). Myo-Inositol in the ACC was negatively correlated with MTSD-Trait scores in both patients (ρ=-0.336, p=0.009) and community comparison samples (ρ=-0.328, p=0.006). Furthermore, patients with a diagnosis of schizoaffective disorder or a history of at least one major depressive episode had lower levels of myo-Inositol compared with schizophrenia patients without a current or past affective diagnosis (p=0.012). Since reduced brain myo-Inositol is associated with MDD, myo-Inositol may be a biochemical marker of depressive mood symptoms across diagnostic boundaries. If confirmed, this finding may aid investigation of the pathophysiology and therapeutics of depression common between depression, schizophrenia and other psychiatric diagnoses.

  10. Inhibition of myo-inositol monophosphatase isoforms by aromatic phosphonates.

    Science.gov (United States)

    Ganzhorn, A J; Hoflack, J; Pelton, P D; Strasser, F; Chanal, M C; Piettre, S R

    1998-10-01

    alpha-Hydroxyphosphonates are moderately potent (Ki = 6-600 microM) inhibitors of the enzyme myo-inositol monophosphatase (McLeod et al., Med. Chem. Res. 1992, 2, 96). Hydroxy-[4-(5,6,7,8-tetrahydronaphtyl-1-oxy)phenyl]methyl phosphonate (3) was resynthesized and its inhibitory potency towards the recombinant bovine brain enzyme confirmed (Ki = 20 microM). Similar aromatic difluoro-, keto-, and ketodifluorophosphonates (5, 7, 9) were inactive. Compound 3 was 15-fold less active on the human as compared to the bovine enzyme. Molecular modeling suggested that the hydrophobic part of the inhibitor interacts with amino acid side chains that are located at the interface between the enzyme subunits in an area (amino acids 175-185) with low similarity between the two isozymes. Phe-183 in the human enzyme was replaced with leucine, the corresponding residue in the bovine isoform. The three isozymes (human wild-type, bovine wild-type and human F183L) had similar kinetic properties, except that the bovine enzyme was less effectively inhibited by high concentrations of the activator Mg2+. The F183L mutant enzyme had a twofold increased affinity for compound 3 as compared to the human wild-type form. We conclude that residue 183 contributes to the binding of aromatic hydroxyphosphonates to IMPase, but it is not the only determining factor for inhibitor specificity with respect to different isozymes.

  11. New sesquiterpene acid and inositol derivatives from Inula montana L.

    Science.gov (United States)

    Garayev, Elnur; Herbette, Gaëtan; Di Giorgio, Carole; Chiffolleau, Philippe; Roux, David; Sallanon, Huguette; Ollivier, Evelyne; Elias, Riad; Baghdikian, Béatrice

    2017-07-01

    A phytochemical investigation of the ethanol extract of leaves and flowers of Inula montana L. led to the isolation of one new sesquiterpene acid called Eldarin (1) and four new inositol derivatives, Myoinositol,1,5-diangelate-4,6-diacetate (2), Myoinositol,1,6-diangelate-4,5-diacetate (3), Myoinositol-1-angelate-4,5-diacetate-6-(2-methylbutirate) (4), Myoinositol-1-angelate-4,5-diacetate-6-isovalerate (5) isolated for the first time, along with eleven known compounds described for the first time in Inula montana, 1β-Hydroxyarbusculin A (6), Artemorin (7), Santamarin (8), Chrysosplenol C (9), 6-Hydroxykaempferol 3,7-dimethyl ether (10), Reynosin (11), Calenduladiol-3-palmitate (12), Costunolide (13), 4-Hydroxy-3,5-dimethoxybenzenemethanol (14), 9β-Hydroxycostunolide (15) and Hispidulin (16). Structural elucidation has been carried out by spectral methods, such as 1D and 2D NMR, IR, UV and HR-ESI-MS. These compounds have been tested in vitro for anti-inflammatory and cytotoxic activity on macrophages RAW 264.7. As a result, compounds 2, 3, 7, 13, 14, 15 and 16 showed a release of NO with IC 50 value <30μM on macrophages. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Inositol 1,4,5-trisphosphate receptors in the heart

    Directory of Open Access Journals (Sweden)

    LAUREN MACKENZIE

    2004-01-01

    Full Text Available Inositol 1,4,5-trisphosphate (InsP3 is an established calcium-mobilizing messenger, which is well-known to activate Ca2+ signaling in many cell types. Contractile cardiomyocytes express hormone receptors that are coupled to the production of InsP3. Such cardioactive hormones, including endothelin, may have profound inotropic and arrhythmogenic actions, but it is unclear whether InsP3 underlies any of these effects. We have examined the expression and localization of InsP3 receptors (InsP3Rs, and the potential role of InsP3 in modulating cardiac excitation-contraction coupling (EC coupling. Stimulation of electrically-paced atrial and ventricular myocytes with a membrane-permeant InsP3 ester was found to evoke an increase in the amplitudes of action potential-evoked Ca2+ transients and to cause pro-arrhythmic diastolic Ca2+ transients. All the effects of the InsP3 ester could be blocked using a membrane-permeant antagonist of InsP3Rs (2-aminoethoxydiphenyl borate; 2-APB. Furthermore, 2-APB blocked arrhythmias evoked by endothelin and delayed the onset of positive inotropic responses. Our data indicate that atrial and ventricular cardiomyocytes express functional InsP3Rs, and these channels have the potential to influence EC coupling.

  13. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    through the formation of β- cyanoalanine, or, potentially, in an alternative endogenous turnover pathway circumventing the release of HCN. The investigation of the latter is the primary focus of this PhD project. Scattered data from the literature indicated that CNglcs co-occur in plants...... revealed the formation of glycosides of amides, carboxylic acids and "anitriles", including their di- and triglycosides, evidently derived from CNglcs. Based on results common to the three phylogenetically unrelated plant species, a recycling endogenous turnover pathway for CNglcs was suggested in which...... with an N-terminal TCP domain, showed that these enzymes do not recognize CNglcs as their substrates. However, the activity of NIT4s on a nitrile glucoside indicates that the enzymatic formation of glycosylated turnover products might be an integral part of the endogenous turnover of CNglcs. The elucidation...

  14. Organisational Commitment, Job Satisfaction and Turnover ...

    African Journals Online (AJOL)

    This study investigated organisational commitment, job satisfaction and turnover intentions among records management personnel in Ondo State Civil Service, Akure, Nigeria. Simple random sampling technique was used to draw 240 subjects from a population size of 275 records management personnel.

  15. Spatial turnover in the global avifauna.

    Science.gov (United States)

    Gaston, Kevin J; Davies, Richard G; Orme, C David L; Olson, Valerie A; Thomas, Gavin H; Ding, Tzung-Su; Rasmussen, Pamela C; Lennon, Jack J; Bennett, Peter M; Owens, Ian P F; Blackburn, Tim M

    2007-07-07

    Despite its wide implications for many ecological issues, the global pattern of spatial turnover in the occurrence of species has been little studied, unlike the global pattern of species richness. Here, using a database on the breeding distributions of birds, we present the first global maps of variation in spatial turnover for an entire taxonomic class, a pattern that has to date remained largely a matter of conjecture, based on theoretical expectations and extrapolation of inconsistent patterns from different biogeographic realms. We use these maps to test four predictions from niche theory as to the form that this variation should take, namely that turnover should increase with species richness, towards lower latitudes, and with the steepness of environmental gradients and that variation in turnover is determined principally by rare (restricted) species. Contrary to prediction, we show that turnover is high both in areas of extremely low and high species richness, does not increase strongly towards the tropics, and is related both to average environmental conditions and spatial variation in those conditions. These results are closely associated with a further important and novel finding, namely that global patterns of spatial turnover are driven principally by widespread species rather than the restricted ones. This complements recent demonstrations that spatial patterns of species richness are also driven principally by widespread species, and thus provides an important contribution towards a unified model of how terrestrial biodiversity varies both within and between the Earth's major land masses.

  16. The Effects of Employee Turnover on Those Who Stay.

    Science.gov (United States)

    Sheehan, Eugene P.; Hockett, Cherri

    Research on employee turnover which has examined why employees quit their jobs has identified a wide range of variables that are associated with turnover, but has provided little information about the consequences of turnover for those who remain in an organization. This study was conducted to examine whether the manner in which turnover is…

  17. Thermoanalytical study of sweetener myo-inositol: α and β polymorphs.

    Science.gov (United States)

    Alarcon, Rafael Turra; Gaglieri, Caroline; Caires, Flávio Junior; Magdalena, Aroldo Geraldo; de Castro, Ricardo António Esteves; Bannach, Gilbert

    2017-12-15

    This work investigates the thermal behavior of α and β myo-inositol polymorphs. The inositol is a natural compound widely used in the food industry due to its presence in carbohydrate metabolism and its sweet taste. The occurrence of polymorphism could change some physico-chemical properties, such as melting and sublimation temperatures, and solubility. Therefore, the thermal study of polymorphism is important to ensure better conditions for synthesis, storage, and transportation of food that contains the myo-inositol. Simultaneous Termogravimetry-Differential Thermal Analysis, Photovisual Differential Scanning Calorimetry, Polarized Light Thermomicroscopy, and Powder X-ray Diffraction were used in investigation. The data show a new thermal event associated to β myo-inositol melting at 221.43°C, suggesting that the solid-solid transition at 185.68°C was incomplete. The kinetics data made it possible to determine the transition lifetime of myo-inositol to occur 5% of solid-solid transition at 20°C and 37°C: 126 and 8years, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Addressing employee turnover and retention: keeping your valued performers.

    Science.gov (United States)

    McConnell, Charles R

    2011-01-01

    Employee turnover and employee retention are inextricably linked; to control turnover is to enhance retention. Turnover is a relatively simple concept; however, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some that can be corrected and some that cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role; every improvement in turnover is a direct improvement in retention, with eventual positive effects on the bottom line.

  19. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change over Time Matters

    Directory of Open Access Journals (Sweden)

    Bryan R. Garner

    2014-01-01

    Full Text Available This study examined the extent to which changes over time in clinicians’ responses to measures of work attitude (eg, job satisfaction and psychological climate (eg, supervisor support could predict actual turnover and turnover intentions above and beyond absolute levels of these respective measures. Longitudinal data for this study were collected from a sample of clinicians ( N = 96 being trained to implement an evidence-based treatment for adolescent substance use disorders. Supporting findings from a recent staff turnover study, we found job satisfaction change was able to predict actual turnover above and beyond average levels of job satisfaction. Representing new contributions to the staff turnover literature, we also found that change over time in several other key measures (eg, job satisfaction, role manageability, role clarity explained a significant amount of variance in turnover intentions above and beyond the absolute level of each respective measure. A key implication of the current study is that organizations seeking to improve their ability to assess risk for staff turnover may want to consider assessing staff at multiple points in time in order to identify systematic changes in key employee attitudes like turnover intentions and job satisfaction.

  20. Lithium modulation of the human inositol monophosphatase 2 (IMPA2) promoter

    International Nuclear Information System (INIS)

    Seelan, Ratnam S.; Parthasarathy, Latha K.; Parthasarathy, Ranga N.

    2004-01-01

    The inositol-signaling pathway is a therapeutic target for lithium in the treatment of bipolar disorder. Inositol monophosphatases (IMPases) play a key role in inositol signaling. Lithium's ability to inhibit IMPase 1 is well known, but its effect on IMPase 2 or on the transcriptional regulation of these genes has not been studied. Here, we report the identification and characterization of the minimal promoter of IMPA2 (encoding IMPase 2) in HeLa (epithelial) and SK-N-AS (neuronal) cells. IMPA2 promoter activity appears to be contributed by different elements in the 5' flanking region, suggesting that the gene is differentially regulated in neuronal and non-neuronal cells. Furthermore, IMPA2 promoter activity in both cell lines is downregulated, in a dose-dependent manner, by lithium after treatment for only 24 h. This effect is also observed in vivo. Our results suggest a possible role for IMPA2 in bipolar disorder

  1. In vivo incorporation of [2-3H]-myo-inositol into frog opsin

    International Nuclear Information System (INIS)

    Fliesler, S.J.; Anderson, R.E.

    1986-01-01

    The in vivo incorporation of [2- 3 H]-myo-inositol into frog retinal rod outer segment membranes was examined. About 25% of the recovered radioactivity was found to be protein-associated. Following acid hydrolysis of this material and extraction with hexane, all the radioactivity remained in the aqueous phase, indicating that the label was not in fatty acids. Following ion exchange column chromatography of the hydrolysate, the major radioactive compound comigrated on TLC with an internal standard of [U- 14 C]-myo-inositol. SDS polyacrylamide gel electrophoresis of unextracted membranes indicated that the majority of the label was associated with opsin. These results indicate that [2- 3 H]-myo-inositol was incorporated in vivo into opsin, presumably with retention of its chemical identity

  2. Determination of free inositols and other low molecular weight carbohydrates in vegetables.

    Science.gov (United States)

    Hernández-Hernández, Oswaldo; Ruiz-Aceituno, Laura; Sanz, María Luz; Martínez-Castro, Isabel

    2011-03-23

    Different low molecular weight carbohydrates including saccharides, polyalcohols, sugar acids, and glycosides have been identified and quantified in different edible vegetables from Asteraceae, Amarantaceae, Amarylidaceae, Brassicaceae, Dioscoreaceae, and Solanaceae families by gas chromatography-mass spectrometry. Apart from glucose, fructose, and sucrose, other saccharides such as sedoheptulose in chicory, spinach, cabbage, purple yam, eggplant, radish, and oak leaf lettuce, rutinose in eggplant skin, and a glycosyl-inositol in spinach have been identified. chiro-Inositol was found in all vegetables of the Asteraceae family (3.1-32.6 mg 100 g(-1)), whereas scyllo-inositol was detected in those of purple yam, eggplant, artichoke, chicory, escarole, and endive (traces-23.2 mg 100 g(-1)). α-Galactosides, kestose, glucaric acid, and glycosyl-glycerols were also identified and quantified in some of the analyzed vegetables. Considering the bioactivity of most of these compounds, mainly chicory leaves, artichokes, lettuces, and purple yam could constitute beneficial sources for human health.

  3. On the correlation between hydrogen bonding and melting points in the inositols

    DEFF Research Database (Denmark)

    Bekö, Sándor L; Alig, Edith; Schmidt, Martin U

    2014-01-01

    Inositol, 1,2,3,4,5,6-hexahydroxycyclohexane, exists in nine stereoisomers with different crystal structures and melting points. In a previous paper on the relationship between the melting points of the inositols and the hydrogen-bonding patterns in their crystal structures [Simperler et al. (2006...... ▶). CrystEngComm 8, 589], it was noted that although all inositol crystal structures known at that time contained 12 hydrogen bonds per molecule, their melting points span a large range of about 170 °C. Our preliminary investigations suggested that the highest melting point must be corrected for the effect...... ordered phases could be determined, of which seven were obtained from laboratory X-ray powder diffraction data. Five additional phases turned out to be rotator phases and only their unit cells could be determined. Two previously unknown melting points were measured, as well as most enthalpies of melting...

  4. The BRCA1 Tumor Suppressor Binds to Inositol 1,4,5-Trisphosphate Receptors to Stimulate Apoptotic Calcium Release*

    Science.gov (United States)

    Hedgepeth, Serena C.; Garcia, M. Iveth; Wagner, Larry E.; Rodriguez, Ana M.; Chintapalli, Sree V.; Snyder, Russell R.; Hankins, Gary D. V.; Henderson, Beric R.; Brodie, Kirsty M.; Yule, David I.; van Rossum, Damian B.; Boehning, Darren

    2015-01-01

    The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein. PMID:25645916

  5. Characterization of a multifunctional inositol phosphate kinase from rice and barley belonging to the ATP-grasp superfamily

    DEFF Research Database (Denmark)

    Josefsen, L.; Bohn, L.; Sørensen, M.B.

    2007-01-01

    OsIpk and HvIk, inositol phosphate kinases, were cloned from rice (Oryza sativa L. var. indica, IR64) and barley (Hordeum vulgare) respectively.. IP Sequence alignment showed that they belong to the ATP-grasp family, which includes inositol 1,3,4-trisphosphate 5/6-kinase from humans and Arabidopsis....... Residues that are binding sites for ATP and coordinate magnesium in absence or presence of inositol phosphate are conserved and in total 23 residues are invariant among the twelve aligned inositol phosphate kinases. The genes were heterologously expressed in Escherichia coli and kinase activity assays...... with 17 different isomers of inositol mono-/di-/tri-/tetra-/pentaphosphate as well as phytate were performed. The strongest activity for both kinases was observed with Ins(3,4,5,6)P-4, which candidates as the primary substrate for these kinases in plants. Several species-specific differences between...

  6. Glutathione turnover in 14 rat tissues

    International Nuclear Information System (INIS)

    Potter, D.W.; Tran, T.

    1990-01-01

    GSH is a tripeptide found in all tissues and is important in maintaining cellular redox status. First-order rate constants for GSH turnover were determined for various tissues of Fischer male rats. Animals were administered [ 35 S]Cys by tail vein injection and GSH turnover was estimated by the decrease in GSH specific activity following incorporation of Cys, 1-102 hr after administration. Tissue nonprotein sulfhydryls (NPSH) were detected by Ellman's assay and compared with GSH and Cys concentrations determined by HPLC with electrochemical detection. [ 35 S]GSH was analyzed by HPLC equipped with a flow-through radioactivity detector. Although total GSH and Cys were usually slightly lower than NPSH concentrations for the tissues examined, both assay systems gave comparable results. An exception was the glandular stomach which had approximately 2-fold higher NPSH. Liver and kidney had rapid turnover rates with GSH half-lives between 2-5 hr, while heart and skeletal muscle tissue had half-lives of 80-90 hr. Turnover in the blood was slowest, with a half-life of 170 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach > duodenum = small intestine = caecum = large intestine = colon > forestomach. GSH half-life in lung and skin was approximately 45 hr. These studies indicate that tissues utilize GSH at markedly different rates

  7. Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.

    Science.gov (United States)

    Dai, Zhijie; Chung, Sookja K; Miao, Dengshun; Lau, Kam S; Chan, Alfred W H; Kung, Annie W C

    2011-03-01

    myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. Copyright © 2011 American Society for Bone and Mineral Research.

  8. Phospholipid biosynthesis in Candida albicans: Regulation by the precursors inositol and choline

    International Nuclear Information System (INIS)

    Klig, L.S.; Friedli, L.; Schmid, E.

    1990-01-01

    Phospholipid metabolism in the pathogenic fungus Candida albicans was examined. The phospholipid biosynthetic pathways of C. albicans were elucidated and were shown to be similar to those of Saccharomyces cerevisiae. However, marked differences were seen between these two fungi in the regulation of the pathways in response to exogenously provided precursors inositol and choline. In S. cerevisiae, the biosynthesis of phosphatidylcholine via methylation of phosphatidylethanolamine appears to be regulated in response to inositol and choline; provision of choline alone does not repress the activity of this pathway. The same pathway in C. albicans responds to the exogenous provision of choline. Possible explanations for the observed differences in regulation are discussed

  9. Formation of Dihydroxybenzenes in Cigarette Smoke. Part 2. Contribution from Quinic Acid and Myo-Inositol

    Directory of Open Access Journals (Sweden)

    Moldoveanu SC

    2014-12-01

    Full Text Available Formation of dihydroxybenzenes in cigarette smoke is a subject of considerable interest because some dihydroxybenzenes are co-carcinogens, (e.g., catechol and certain alkylcatechols, and others such as hydroquinone can form metabolites that have toxic or carcinogenic properties. This present study describes the contribution of tobacco quinic acid (or (1S,3R,4S,5R-1,3,4,5-tetrahydroxycyclohexanecarboxylic acid and myo-inositol (or (1R,2R,3S,4S,5R,6S-cyclohexane-1,2,3,4,5,6-hexol to the formation of dihydroxybenzenes in cigarette smoke. The study is a continuation of a previous one showing the contribution of chlorogenic acid and rutin as precursors for these compounds (6. The yields of dihydroxybenzenes formed by pyrolysis of quinic acid and myo-inositol are relatively high and both quinic acid and myo-inositol can be present in some tobacco types at levels as high as 1% by weight. The level of these compounds makes them potentially important contributors to the formation of dihydroxybenzenes in cigarette smoke. Similar to the previous study on other dihydroxybenzene precursors from tobacco, this present study was done in three parts: 1 pyrolytic evaluation of the amount of dihydroxybenzenes in smoke generated from isolated quinic acid and myoinositol; 2 analysis of smoke from cigarettes made from a variety of tobaccos (14 single grades and two blended cigarettes, followed by correlations of dihydroxybenzene yields from these cigarettes with the level of quinic acid and myo-inositol in the tobaccos; 3 addition of quinic acid or myo-inositol to several tobaccos followed by the smoking of the spiked cigarettes and measurement of the dihydroxybenzenes yield increase. The study performed on a variety of single-grade tobacco cigarettes and for two blended-tobacco cigarettes (one being the 2R4F Kentucky reference shows that the contribution of quinic acid and of inositol to the formation of catechol and hydroquinone in smoke depends on the blend, as

  10. Anti-inflammatory Inositol Derivatives from the Whole Plant of Inula cappa.

    Science.gov (United States)

    Wu, Jiewei; Tang, Chunping; Yao, Sheng; Zhang, Lei; Ke, Changqiang; Feng, Linyin; Lin, Ge; Ye, Yang

    2015-10-23

    Twelve new inositol derivatives, classified into myoinositol (1-6) and l-inositol (10-15) types, along with five known analogues were isolated from the whole plant of Inula cappa. The structures of the new compounds were established by extensive analysis of mass spectrometric and 1D and 2D NMR spectroscopic data. All the tested compounds showed anti-inflammatory activities against the production of NO in RAW264.7 macrophages stimulated by lipopolysaccharide, with IC50 values ranging from 7 to 23 μM.

  11. Regulation of myo-inositol catabolism by a GntR-type repressor SCO6974 in Streptomyces coelicolor.

    Science.gov (United States)

    Yu, Lingjun; Li, Shuxian; Gao, Wenyan; Pan, Yuanyuan; Tan, Huarong; Liu, Gang

    2015-04-01

    Myo-inositol is important for Streptomyces growth and morphological differentiation. Genomic sequence analysis revealed a myo-inositol catabolic gene cluster in Streptomyces coelicolor. Disruption of the corresponding genes in this cluster abolished the bacterial growth on myo-inositol as a single carbon source. The transcriptions of these genes were remarkably enhanced by addition of myo-inositol in minimal medium. A putative regulatory gene SCO6974, encoding a GntR family protein, is situated in the cluster. Disruption of SCO6974 significantly enhanced the transcription of myo-inositol catabolic genes. SCO6974 was shown to interact with the promoter regions of myo-inositol catabolic genes using electrophoretic mobility shift assays. DNase I footprinting assays demonstrated that SCO6974 recognized a conserved palindromic sequence (A/T)TGT(A/C)N(G/T)(G/T)ACA(A/T). Base substitution of the conserved sequence completely abolished the binding of SCO6974 to the targets demonstrating that SCO6974 directly represses the transcriptions of myo-inositol catabolic genes. Furthermore, the disruption of SCO6974 was correlated with a reduced sporulation of S. coelicolor in mannitol soya flour medium and with the overproduction of actinorhodin and calcium-dependent antibiotic. The addition of myo-inositol suppressed the sporulation deficiency of the mutant, indicating that the effect could be related to a shortage in myo-inositol due to its enhanced catabolism in this strain. This enhanced myo-inositol catabolism likely yields dihydroxyacetone phosphate and acetyl-CoA that are indirect or direct precursors of the overproduced antibiotics.

  12. Changes of Protein Turnover in Aging Caenorhabditis elegans.

    Science.gov (United States)

    Dhondt, Ineke; Petyuk, Vladislav A; Bauer, Sophie; Brewer, Heather M; Smith, Richard D; Depuydt, Geert; Braeckman, Bart P

    2017-09-01

    Protein turnover rates severely decline in aging organisms, including C. elegans However, limited information is available on turnover dynamics at the individual protein level during aging. We followed changes in protein turnover at one-day resolution using a multiple-pulse 15 N-labeling and accurate mass spectrometry approach. Forty percent of the proteome shows gradual slowdown in turnover with age, whereas only few proteins show increased turnover. Decrease in protein turnover was consistent for only a minority of functionally related protein subsets, including tubulins and vitellogenins, whereas randomly diverging turnover patterns with age were the norm. Our data suggests increased heterogeneity of protein turnover of the translation machinery, whereas protein turnover of ubiquitin-proteasome and antioxidant systems are well-preserved over time. Hence, we presume that maintenance of quality control mechanisms is a protective strategy in aging worms, although the ultimate proteome collapse is inescapable. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Reducing voluntary, avoidable turnover through selection.

    Science.gov (United States)

    Barrick, Murray R; Zimmerman, Ryan D

    2005-01-01

    The authors investigated the efficacy of several variables used to predict voluntary, organizationally avoidable turnover even before the employee is hired. Analyses conducted on applicant data collected in 2 separate organizations (N = 445) confirmed that biodata, clear-purpose attitudes and intentions, and disguised-purpose dispositional retention scales predicted voluntary, avoidable turnover (rs ranged from -.16 to -.22, R = .37, adjusted R = .33). Results also revealed that biodata scales and disguised-purpose retention scales added incremental validity, whereas clear-purpose retention scales did not explain significant incremental variance in turnover beyond what was explained by biodata and disguised-purpose scales. Furthermore, disparate impact (subgroup differences on race, sex, and age) was consistently small (average d = 0.12 when the majority group scored higher than the minority group).

  14. Preliminary Investigation of Myo-Inositol Phosphates Produced by ASUIA279 Phytase on MCF-7 Cancer Cells

    Directory of Open Access Journals (Sweden)

    N. Mohd. Yusoff

    2011-12-01

    Full Text Available Phytate or myo-inositol hexakisphosphates (IP6 is widely distributed in plants like rice brans. The production of myo-inositol phosphate intermediates has received much attention due to the remarkable potential health benefits offered by the compounds. In this study, the cytotoxicity of the partially purified myo-inositol phosphate fractions and commercial IP1 and IP6 were investigated against MCF-7 breast cancer cell lines. The study showed that the commercial standard IP1 and IP6 showed good inhibition towards the MCF-7 cell line. The MCF-7 cells growth was inhibited in minimum concentration of myo-inositol phosphates (<1000 µg/ml. However, no inhibition observed on the MCF-7 cell line by the myo-inositol phosphates fractions partially purified from rice bran at concentration <1000 ?g/ml. The inhibition of MCF-7 was only observed at concentration more than 30 mg/ml with more than 40% cells were inhibited. This indicates that the partially purified rice bran myo-inositol phosphates degraded by ASUIA279 phytase on MCF-7 breast cancer cells exhibit positive results towards the inhibition of cancer cells growth at relatively high concentration..KEYWORDS: myo-inositol phosphates, phytase, MCF-7,  cancerABSTRAK: Fitat atau myo-inositol hexakisphosphate (IP6 dikenali umum teragih di dalam tumbuhan seperti dedak padi. Penghasilan perantaraan fosfat myo-inositol mendapat perhatian memandangkan ia berpotensi tinggi dalam kesihatan. Dalam kajian ini, kesitotoksikan sebahagian daripada fosfat myo-inositol separa tulen, IP1 komersil dan IP6 komersil dikaji terhadap produk yang berupa sel kekal (cell lines kanser payu dara MCF-7. Tumbesaran sel MCF-7 direncatkan dalam pekatan minima fosfat myo-inositol (<1000 μg/ml. Tetapi, tidak ada perencatan dilihat terhadap sel kekal MCF-7 oleh sebahagian fosfat myo-inositol separa tulen daripada dedak padi pada kepekatan <1000 mg/ml. Perencatan MCF-7 hanya dilihat pada kepekatan lebih daripada 30 mg/ml dengan lebih

  15. Aberrant 3H in Ehrlich mouse ascites tumor cell nucleotides after in vivo labeling with myo-[2-3H]- and L -myo-[1-3H]inositol: implications for measuring inositol phosphate signaling

    DEFF Research Database (Denmark)

    Christensen, Søren C.; Jensen, Annelie Kolbjørn; Simonsen, L.O.

    2003-01-01

    After in vivo radiolabeling of Ehrlich cells for 24 h with conventional myo-[2-3H]inositol we previously demonstrated an aberrant 3H-labeling of ATP that interfered in the HPLC analysis of inositol trisphosphates. This aberrant 3H-labeling was accounted for by the extensive kidney catabolism of myo......-[2-3H] inositol with delivery of 3H-labeled metabolites to extrarenal tissues. As expected, the aberrant labeling of ATP is markedly reduced with the use of 3H-myo-inositol labeled at L-C1 rather than at C2, reflecting that the 3H at L-C1 disappears in the first step of the myo-inositol catabolism......: the oxidative conversion to -glucuronate. In contrast, with the 3H at C2 of myo-inositol, the 3H-C2 passes into the pentose phosphate conversions with resulting labeling of nucleotides. The extent of catabolism to 3H-labeled water, the cellular accumulation of 3H-myo-inositol, the incorporation into cellular...

  16. Inositol phosphates influence the membrane bound Ca2+/Mg2+ stimulated ATPase from human erythrocyte membranes

    International Nuclear Information System (INIS)

    Kester, M.; Ekholm, J.; Kumar, R.; Hanahan, D.J.

    1986-01-01

    The modulation by exogenous inositol phosphates of the membrane Ca 2+ /Mg 2+ ATPase from saponin/EGTA lysed human erythrocytes was determined in a buffer (pH 7.6) containing histidine, 80 mM, MgCl 2 , 3.3 mM, NaCl, 74 mM, KCl, 30 mM, Na 2 ATP, 2.3 mM, ouabain, 0.83 mM, with variable amounts of CaCl 2 and EGTA. The ATPase assay was linear with time at 44 0 C. The inositol phosphates were commercially obtained and were also prepared from 32 P labeled rabbit platelet inositol phospholipids. Inositol triphosphate (IP 3 ) elevated the Ca 2+ /Mg 2+ ATPase activity over basal levels in a dose, time, and calcium dependent manner and were increased up to 85% of control values. Activities for the Na + /K + -ATPase and a Mg 2+ ATPase were not effected by IP 3 . Ca 2+ /Mg 2+ APTase activity with IP 2 or IP 3 could be synergistically elevated with calmodulin addition. The activation of the ATPase with IP 3 was calcium dependent in a range from .001 to .02 mM. The apparent Km and Vmax values were determined for IP 3 stimulated Ca 2+ /Mg 2+ ATPase

  17. How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

    Directory of Open Access Journals (Sweden)

    Salvatore Giovanni Vitale

    2016-01-01

    Full Text Available Assisted reproductive technologies (ART have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

  18. How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

    Science.gov (United States)

    Rossetti, Paola; Corrado, Francesco; Rapisarda, Agnese Maria Chiara; Condorelli, Rosita Angela; Valenti, Gaetano; Sapia, Fabrizio; Buscema, Massimo

    2016-01-01

    Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment. PMID:27651794

  19. Dephosphorylation of myo-inositol phosphates in the in vitro intestinal Caco-2 cell model.

    Science.gov (United States)

    Briviba, Karlis; Schollenberger, Margit; Rodehutscord, Markus; Greiner, Ralf

    2018-02-01

    Plant and microbial phytases present in raw materials can cause a dephosphorylation of phytate (myo-inositol hexakisphosphate) (InsP 6 )) during food processing resulting in a broad range of different myo-inositol phosphates such as pentakisphosphate (InsP 5 ) and tetrakisphosphate (InsP 4 ) in foods. Here, we investigated whether the human intestinal epithelium is able to dephosphorylate myo-inositol phosphates (InsP 6 , InsP 5 -, InsP 4 -, InsP 3 -isomers) using an in vitro model with differentiated human Caco-2 cells cultured on semipermeable inserts. Incubation of InsP 6 and an InsP 5 -isomer with cells for 3 h showed no dephosphorylation of both InsPs. Treatment of cells with a mixture of different InsP 4 -isomers, however, caused a formation of about 3.5% of an InsP 3 -isomer (Ins(1,5,6)P 3 ) and treatment with a mixture of different InsP 3 -isomers caused about 20% formation of InsP 2 -isomers, respectively. Thus, human intestinal cells can contribute to the dephosphorylation of myo-inositol phosphates of partly dephosphorylated forms such as InsP 3 and InsP 4 .

  20. myo-Inositol-1-phosphate synthase is required for polar auxin transport and organ development

    KAUST Repository

    Chen, Hao

    2010-06-01

    myo-Inositol-1-phosphate synthase is a conserved enzyme that catalyzes the first committed and rate-limiting step in inositol biosynthesis. Despite its wide occurrence in all eukaryotes, the role of myo-inositol-1-phosphate synthase and de novo inositol biosynthesis in cell signaling and organism development has been unclear. In this study, we isolated loss-of-function mutants in the Arabidopsis MIPS1 gene from different ecotypes. It was found that all mips1 mutants are defective in embryogenesis, cotyledon venation patterning, root growth, and root cap development. The mutant roots are also agravitropic and have reduced basipetal auxin transport. mips1 mutants have significantly reduced levels of major phosphatidylinositols and exhibit much slower rates of endocytosis. Treatment with brefeldin A induces slower PIN2 protein aggregation in mips1, indicating altered PIN2 trafficking. Our results demonstrate that MIPS1 is critical for maintaining phosphatidylinositol levels and affects pattern formation in plants likely through regulation of auxin distribution. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Myo-inositol, glucose and zinc concentrations determined in the preconceptional period, during and after pregnancy.

    NARCIS (Netherlands)

    Groenen, P.M.; Roes, E.M.; Peer, P.G.M.; Merkus, H.M.; Steegers, E.A.P.; Steegers-Theunissen, R.P.M.

    2006-01-01

    OBJECTIVE: To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy. STUDY DESIGN: Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and

  2. Genetic control of lithium sensitivity and regulation of inositol biosynthetic genes.

    Directory of Open Access Journals (Sweden)

    Jason King

    2010-06-01

    Full Text Available Lithium (Li(+ is a common treatment for bipolar mood disorder, a major psychiatric illness with a lifetime prevalence of more than 1%. Risk of bipolar disorder is heavily influenced by genetic predisposition, but is a complex genetic trait and, to date, genetic studies have provided little insight into its molecular origins. An alternative approach is to investigate the genetics of Li(+ sensitivity. Using the social amoeba Dictyostelium, we previously identified prolyl oligopeptidase (PO as a modulator of Li(+ sensitivity. In a link to the clinic, PO enzyme activity is altered in bipolar disorder patients. Further studies demonstrated that PO is a negative regulator of inositol(1,4,5trisphosphate (IP(3 synthesis, a Li(+ sensitive intracellular signal. However, it was unclear how PO could influence either Li(+ sensitivity or risk of bipolar disorder. Here we show that in both Dictyostelium and cultured human cells PO acts via Multiple Inositol Polyphosphate Phosphatase (Mipp1 to control gene expression. This reveals a novel, gene regulatory network that modulates inositol metabolism and Li(+ sensitivity. Among its targets is the inositol monophosphatase gene IMPA2, which has also been associated with risk of bipolar disorder in some family studies, and our observations offer a cellular signalling pathway in which PO activity and IMPA2 gene expression converge.

  3. Impact of different levels of dietary myo-inositol on the growth ...

    African Journals Online (AJOL)

    USER

    2010-07-26

    Jul 26, 2010 ... MI is a structural component of biological membranes in the phospholipid form, Inositol phospholipds and their metabolites are universal second messengers in the signal transduction pathway. Biochemical functions of phosphatidylinositol include the mediation of cellular responses to external stimuli,.

  4. Nutritional and environmental factors in human spina bifida : an emphasis on myo-inositol

    NARCIS (Netherlands)

    Groenen, Pascal Martinus Wilhelmus

    2004-01-01

    This thesis describes the results of a nation wide case-control triad study carried out in collaboration with nine spina bifida centers and a patient organization (VSOP/BOSK) focused on the role of myo-inositol and zinc, environmental factors and related genes in the pathogenesis of spina bifida.

  5. Inositol Trisphosphate-Induced Ca2+ Signaling Modulates Auxin Transport and PIN Polarity

    Czech Academy of Sciences Publication Activity Database

    Zhang, J.; Vanneste, S.; Brewer, P. B.; Michniewicz, M.; Grones, P.; Kleine-Vehn, J.; Löfke, Ch.; Teichmann, T.; Bielach, A.; Cannoot, B.; Hoyerová, Klára; Chen, X.; Xue, H. W.; Benková, E.; Zažímalová, Eva; Friml, J.

    2011-01-01

    Roč. 20, č. 6 (2011), s. 855-866 ISSN 1534-5807 Institutional research plan: CEZ:AV0Z50380511 Keywords : PIN polarity * auxin distribution * Inositol trisphosphate Subject RIV: ED - Physiology Impact factor: 14.030, year: 2011

  6. Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Sanborn, B.B.; Schneider, A.S.

    1990-01-01

    Inositol trisphosphate (IP 3 ), a product of the phosphoinositide cycle, mobilizes intracellular Ca 2+ in many cell types. New evidence suggests that inositol tetrakisphosphate (IP 4 ), an IP 3 derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP 4 are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP 4 in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine stimulated an increase in [ 3 H]IP 4 and [ 3 H]IP 3 accumulation in chromaffin cells and this effect was completely blocked by atropine. [ 3 H]IP 4 accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP 3 and IP 4 hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP 4 and calcium homeostasis

  7. Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.

    Science.gov (United States)

    Sajja, Venkata Siva Sai Sujith; Perrine, Shane A; Ghoddoussi, Farhad; Hall, Christina S; Galloway, Matthew P; VandeVord, Pamela J

    2014-03-01

    Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Altered coupling between aortic adrenergic-receptors and inositol phosphate accumulation in aldosterone hypertension

    International Nuclear Information System (INIS)

    Jones, A.W.; Bylund, D.B.; Shukla, S.D.; Magliola, L.; Smith, J.M.; Ray-Pranger, C.; Bailey, B.

    1986-01-01

    The authors previous studies of 42 K efflux have shown a 6-10 fold increase in sensitivity to α-receptor agonists in aortas from rats (AHR) made hypertensive with aldosterone infusion, uninephrectomy plus high salt intake. Analyses of α-receptor properties, however, showed no significant difference in sub-type, affinity or maximum binding. They initiated this study to determine whether supersensitivity is associated with altered accumulation of inositol phosphates. Aortic strips were equilibrated in 3 H-inositol PSS for 2 hrs, followed by 10 min exposures to inositol (10 mM) PSS then Li (10 mM) PSS. Strips were placed in Li-PSS +/- norepinephrine (NE) for 30 minutes followed by freeze clamping and analyses of inositol phosphates (IP, IP 2 , IP 3 ) by standard methods. In controls (C) NE (3 μM) increased the CPM 2, 14, and 9 fold respectively (p 2 . NE = 3 μM yielded similar CPM per cell water in C (n=6) and AHR (n=5). The EC 50 for AHR was 5-6 fold lower than C for IP (56 +/- 18 versus 300 +/- 130 nM, p 2 (57 +/- 14 versus 410 +/- 60 nM, p 2 , while supersensitivity in AHR is associated with an increased efficacy in coupling between α-receptors and polyphosphoinositide metabolism

  9. Myo-inositol improves the host’s ability to eliminate balofloxacin-resistant Escherichia coli

    Science.gov (United States)

    Chen, Xin-hai; Zhang, Bing-wen; Li, Hui; Peng, Xuan-xian

    2015-01-01

    Antibiotic-resistant mechanisms are associated with fitness costs. However, why antibiotic-resistant bacteria usually show increasing adaptation to hosts is largely unknown, especially from the host’s perspective. The present study reveals the host’s varied response to balofloxacin-resistant Escherichia coli (BLFX-R) using an integrated proteome and metabolome approach and identifies myo-inositol and phagocytosis-related proteins as crucial biomarkers. Originally, macrophages have an optimal attractive preference to BLFX-S due to more polarization of BLFX-S than BLFX-R, which renders faster elimination to BLFX-S than BLFX-R. The slower elimination to BLFX-R may be reversed by exogenous myo-inositol. Primarily, myo-inositol depolarizes macrophages, elevating adherence to both BLFX-S and BLFX-R. Since the altered adherence is equal to both strains, the myo-inositol-treated macrophages are free of the barrier to BLFX-R and thereby promote phagocytosis of BLFX-R. This work provides a novel strategy based on metabolic modulation for eliminating antibiotic-resistant bacteria with a high degree of host adaptation. PMID:26030712

  10. Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain

    DEFF Research Database (Denmark)

    Verma, A; Hirsch, D J; Hanley, M R

    1990-01-01

    microM. Inositol-1,4,5-trisphosphate (IP3) maximally inhibits 40% of the net Ca2+ accumulation by whole brain microsomes. Its effects are non-additive with thapsigargin suggesting that the IP3-sensitive Ca2+ pool is a subset of the thapsigargin sensitive Ca2+ pool. Marked regional differences occur...

  11. Nutritional and environmental factors in human spina bifida - An emphasis on myo-inositol.

    NARCIS (Netherlands)

    Groenen, P.

    2004-01-01

    This thesis describes the results of a nation wide case-control triad study carried out in collaboration with nine spina bifida centers and a patient organization (VSOP/BOSK) focused on the role of myo-inositol and zinc, environmental factors and related genes in the pathogenesis of spina bifida.

  12. On the correlation between hydrogen bonding and melting points in the inositols

    Directory of Open Access Journals (Sweden)

    Sándor L. Bekö

    2014-01-01

    Full Text Available Inositol, 1,2,3,4,5,6-hexahydroxycyclohexane, exists in nine stereoisomers with different crystal structures and melting points. In a previous paper on the relationship between the melting points of the inositols and the hydrogen-bonding patterns in their crystal structures [Simperler et al. (2006. CrystEngComm 8, 589], it was noted that although all inositol crystal structures known at that time contained 12 hydrogen bonds per molecule, their melting points span a large range of about 170 °C. Our preliminary investigations suggested that the highest melting point must be corrected for the effect of molecular symmetry, and that the three lowest melting points may need to be revised. This prompted a full investigation, with additional experiments on six of the nine inositols. Thirteen new phases were discovered; for all of these their crystal structures were examined. The crystal structures of eight ordered phases could be determined, of which seven were obtained from laboratory X-ray powder diffraction data. Five additional phases turned out to be rotator phases and only their unit cells could be determined. Two previously unknown melting points were measured, as well as most enthalpies of melting. Several previously reported melting points were shown to be solid-to-solid phase transitions or decomposition points. Our experiments have revealed a complex picture of phases, rotator phases and phase transitions, in which a simple correlation between melting points and hydrogen-bonding patterns is not feasible.

  13. Involvement of FST1 from Fusarium verticillioides in virulence and transport of inositol.

    Science.gov (United States)

    Niu, Chenxing; Payne, Gary A; Woloshuk, Charles P

    2017-06-01

    Fumonisin B1 (FB1), a polyketide mycotoxin produced by Fusarium verticillioides during the colonization of maize kernels, is detrimental to human and animal health. FST1 encodes a putative protein with 12 transmembrane domains; however, its function remains unknown. The FST1 gene is highly expressed by the fungus in the endosperm of maize kernels compared with the levels of expression in germ tissues. Previous research has shown that FST1 affects FB1 production, virulence, hydrogen peroxide resistance, hydrophobicity and macroconidia production. Here, we examine the phylogeny of FST1, its expression in a Saccharomyces cerevisiae strain lacking a functional myo-inositol transporter (ITR1) and the effect of amino acid changes in the central loop and C-terminus regions of FST1 on functionality. The results indicate that expression of FST1 in an ITR1 mutant strain restores growth on myo-inositol medium to wild-type levels and restores the inhibitory effects of FB1, suggesting that FST1 can transport both myo-inositol and FB1 into yeast cells. Our results with engineered FST1 also indicate that amino acids in the central loop and C-terminus regions are important for FST1 functionality in both S. cerevisiae and F. verticillioides. Overall, this research has established the first characterized inositol transporter in filamentous fungi and has advanced our knowledge about the global regulatory functions of FST1. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  14. Incorporation of 14C-linoleic acid in lipids of normal and psoriatic human skin

    International Nuclear Information System (INIS)

    Ruestow, B.; Metz, D.; Kunze, D.; Meffert, H.

    1980-01-01

    The 14 C-linoleic acid incorporation in lipids of surviving epidermis and corium of normal and psoriatic human skin was investigated. Changes of lipid metabolism were found in both epidermis and corium. Particularly the turnover of phospholipids was increased in the uninvolved psoriatic epidermis in relation to the involved psoriatic epidermis or to healthy controls. Possible reasons of these phenomena and the significance of structural lipids in psoriasis are discussed. (author)

  15. GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

    International Nuclear Information System (INIS)

    Zhu Zhiming; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin

    2005-01-01

    We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, β-myosin heavy chain, and α-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway

  16. The separation of [32P]inositol phosphates by ion-pair chromatography: Optimization of the method and biological applications

    International Nuclear Information System (INIS)

    Sulpice, J.C.; Gascard, P.; Journet, E.; Rendu, F.; Renard, D.; Poggioli, J.; Giraud, F.

    1989-01-01

    We have developed an ion-pair reverse-phase HPLC method to measure inositol phosphates in 32 P-labeled cells. The different chromatographic parameters were analyzed to optimize the resolution of the 32 P-labeled metabolites. Analysis of inositol phosphates in biological samples was improved by a single charcoal pretreatment which eliminated interfering nucleotides without removing inositol phosphates. The kinetics of production of inositol phosphates in calcium-activated erythrocytes, vasopressin-stimulated hepatocytes, and thrombin-activated platelets were analyzed. Original data on the activation of phosphoinositide phospholipase C were obtained in intact erythrocytes by direct measurement of inositol (1,4,5)P3. Data from agonist-stimulated hepatocytes and platelets were consistent with those from previous studies. In conclusion, this technique offers many advantages over the methodologies currently employed involving anion-exchange chromatography and [ 3 H]inositol labeling: (i) 32 P labeling is less expensive and more efficient than 3 H labeling and can be used with all types of cells without permeabilization treatments and (ii) ion-pair HPLC gives good resolution of inositol phosphates from nucleotides with shorter retention times, and long reequilibration periods are not required

  17. Finding the sweet spot: how human fungal pathogens acquire and turn the sugar inositol against their hosts.

    Science.gov (United States)

    Xue, Chaoyang

    2015-03-03

    Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio 5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species--obligate fungal pathogens that remain unculturable in vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth in vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens. Copyright © 2015 Xue.

  18. A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production.

    Science.gov (United States)

    Tanaka, Kosei; Natsume, Ayane; Ishikawa, Shu; Takenaka, Shinji; Yoshida, Ken-Ichi

    2017-04-21

    A stereoisomer of inositol, scyllo-inositol (SI), has been regarded as a promising therapeutic agent for Alzheimer's disease. However, this compound is relatively rare, whereas another stereoisomer of inositol, myo-inositol (MI) is abundant in nature. Bacillus subtilis 168 has the ability to metabolize inositol stereoisomers, including MI and SI. Previously, we reported a B. subtilis cell factory with modified inositol metabolism that converts MI into SI in the culture medium. The strain was constructed by deleting all genes related to inositol metabolism and overexpressing key enzymes, IolG and IolW. By using this strain, 10 g/l of MI initially included in the medium was completely converted into SI within 48 h of cultivation in a rich medium containing 2% (w/v) Bacto soytone. When the initial concentration of MI was increased to 50 g/l, conversion was limited to 15.1 g/l of SI. Therefore, overexpression systems of IolT and PntAB, the main transporter of MI in B. subtilis and the membrane-integral nicotinamide nucleotide transhydrogenase in Escherichia coli respectively, were additionally introduced into the B. subtilis cell factory, but the conversion efficiency hardly improved. We systematically determined the amount of Bacto soytone necessary for ultimate conversion, which was 4% (w/v). As a result, the conversion of SI reached to 27.6 g/l within 48 h of cultivation. The B. subtilis cell factory was improved to yield a SI production rate of 27.6 g/l/48 h by simultaneous overexpression of IolT and PntAB, and by addition of 4% (w/v) Bacto soytone in the conversion medium. The concentration of SI was increased even in the stationary phase perhaps due to nutrients in the Bacto soytone that contribute to the conversion process. Thus, MI conversion to SI may be further optimized via identification and control of these unknown nutrients.

  19. Antecedents of Norwegian Beginning Teachers' Turnover Intentions

    Science.gov (United States)

    Tiplic, Dijana; Brandmo, Christian; Elstad, Eyvind

    2015-01-01

    This study aims at exploring several individual, organizational, and contextual factors that may affect beginning teachers' turnover intentions during their first years of practice. The sample consists of 227 beginning teachers (69% female and 31% male) from 133 schools in Norway. The results show four important antecedents of beginning teachers'…

  20. Health care workplace discrimination and physician turnover.

    Science.gov (United States)

    Nunez-Smith, Marcella; Pilgrim, Nanlesta; Wynia, Matthew; Desai, Mayur M; Bright, Cedric; Krumholz, Harlan M; Bradley, Elizabeth H

    2009-12-01

    To examine the association between physician race/ ethnicity, workplace discrimination, and physician job turnover. Cross-sectional, national survey conducted in 2006-2007 of practicing physicians (n = 529) randomly identified via the American Medical Association Masterfile and the National Medical Association membership roster. We assessed the relationships between career racial/ethnic discrimination at work and several career-related dependent variables, including 2 measures of physician turnover, career satisfaction, and contemplation of career change. We used standard frequency analyses, odds ratios and chi2 statistics, and multivariate logistic regression modeling to evaluate these associations. Physicians who self-identified as nonmajority were significantly more likely to have left at least 1 job because of workplace discrimination (black, 29%; Asian, 24%; other race, 21%; Hispanic/Latino, 20%; white, 9%). In multivariate models, having experienced racial/ethnic discrimination at work was associated with high job turnover (adjusted odds ratio, 2.7; 95% CI, 1.4-4.9). Among physicians who experienced workplace discrimination, only 45% of physicians were satisfied with their careers (vs 88% among those who had not experienced workplace discrimination, p value workplace discrimination, p value Workplace discrimination is associated with physician job turnover, career dissatisfaction, and contemplation of career change. These findings underscore the importance of monitoring for workplace discrimination and responding when opportunities for intervention and retention still exist.

  1. A Turnover Model for the Mexican Maquiladoras.

    Science.gov (United States)

    Maertz, Carl P.; Stevens, Michael J.; Campion, Michael A.

    2003-01-01

    From interviews with 47 Mexican maquiladora workers, a model of voluntary turnover was created and compared with models from the United States, Canada, England, and Australia. Despite similarities, the cultural and economic environment affected the precise content of antecedents in the Mexican model. (Contains 63 references.) (SK)

  2. Primary care physician turnover in HMOs.

    Science.gov (United States)

    Kerstein, J; Pauly, M V; Hillman, A

    1994-01-01

    OBJECTIVE. We assess whether physician turnover stems from incorrect physician expectations about the practice environment or from actual constraints or rewards in that environment. DATA SOURCES. Our primary data source contains information about individual HMOs' primary care physicians incentive mechanisms and general HMO characteristics. Our secondary data source is the area resource file (ARF), which contains countywide information about the HMOs' market areas, including physician characteristics, population characteristics, and other market characteristics. DATA COLLECTION. Our primary data source is from a nationwide survey of all HMOs in operation in 1987-1988, as reported to Interstudy. PRINCIPAL FINDINGS. We find that turnover is higher on the part of physicians whose HMO enrollment comprises a greater percentage of their total practice. Our results further indicate that physicians whose compensation is dependent on the behavior of a group of other physicians are more likely to leave the plan than those who bear the risk (and control it) more directly. On the other hand, turnover is increased by basing bonuses on individual productivity and by not sharing surpluses among a group. Market characteristics also are significant in explaining physician turnover in HMOs. CONCLUSIONS. It appears that physicians accurately forecast how they will react to individual financial risk, although they dislike restrictions imposed by HMOs. PMID:8163378

  3. Does Judge Turnover Affect Judicial Performance?

    DEFF Research Database (Denmark)

    Guerra, Alice; Tagliapietra, Claudio

    2017-01-01

    Italy is among the countries with the highest litigation rate and those with the highest duration of trials. This article shows that judge turnover contributes negatively to delays in Italian courts and outlines possible policies for improvement. In Italy, judges can voluntarily move from one off...

  4. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    International Nuclear Information System (INIS)

    Carter, M.G.; Shukla, S.D.

    1987-01-01

    Human platelet concentrate from the American Red Cross Blood Center was stored at 24 degree C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying 32 P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 x 10 -7 M PAF at 37 degree C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for 32 P-phosphoinositides. The percent stimulation of 32 P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage

  5. Rapid turnover of effectors in grass powdery mildew (Blumeria graminis).

    Science.gov (United States)

    Menardo, Fabrizio; Praz, Coraline R; Wicker, Thomas; Keller, Beat

    2017-10-31

    Grass powdery mildew (Blumeria graminis, Ascomycota) is a major pathogen of cereal crops and has become a model organism for obligate biotrophic fungal pathogens of plants. The sequenced genomes of two formae speciales (ff.spp.), B.g. hordei and B.g. tritici (pathogens of barley and wheat), were found to be enriched in candidate effector genes (CEGs). Similar to other filamentous pathogens, CEGs in B. graminis are under positive selection. Additionally, effectors are more likely to have presence-absence polymorphisms than other genes among different strains. Here we identified effectors in the genomes of three additional host-specific lineages of B. graminis (B.g. poae, B.g. avenae and B.g. infecting Lolium) which diverged between 24 and 5 million years ago (Mya). We found that most CEGs in B. graminis are clustered in families and that most families are present in both reference genomes (B.g. hordei and B.g. tritici) and in the genomes of all three newly annotated lineages. We identified conserved protein domains including a novel lipid binding domain. The phylogenetic analysis showed that frequent gene duplications and losses shaped the diversity of the effector repertoires of the different lineages through their evolutionary history. We observed several lineage-specific expansions where large clades of CEGs originated in only one lineage from a single gene through repeated gene duplications. When we applied a birth-death model we found that the turnover rate (the rate at which genes are deleted and duplicated) of CEG families is much higher than for non-CEG families. The analysis of genomic context revealed that the immediate surroundings of CEGs are enriched in transposable elements (TE) which could play a role in the duplication and deletion of CEGs. The CEG repertoires of related pathogens diverged dramatically in short evolutionary times because of rapid turnover and of positive selection fixing non-synonymous mutations. While signatures of positive

  6. Time-series responses of swine plasma metabolites to ingestion of diets containing myo-inositol or phytase.

    Science.gov (United States)

    Cowieson, Aaron J; Roos, Franz F; Ruckebusch, Jean-Paul; Wilson, Jonathan W; Guggenbuhl, Patrick; Lu, Hang; Ajuwon, Kolapo M; Adeola, Olayiwola

    2017-12-01

    The effect of the ingestion of diets containing either myo-inositol or exogenous phytase on plasma metabolites was examined using 29 kg barrows. The diets were: control (maize, soya, rapeseed, rice bran), control plus 2 g/kg myo-inositol, control plus 1000 phytase units (FYT)/kg or 3000 FYT/kg exogenous phytase. Pigs were housed in a PigTurn device and blood was collected, from jugular catheters, via an automated system at -30, (30 min before feeding), 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360 min post-feeding. The addition of 2 g/kg myo-inositol to the basal diet resulted in an increase in plasma myo-inositol concentration that was evident 45-60 min after diet introduction and persisted to 360 min post-feeding. Similarly, supplementation of the basal diet with either 1000 or 3000 FYT/kg exogenous phytase resulted in an increase in plasma myo-inositol concentration that was still rising 360 min post-feeding. Plasma P concentration was increased over time by the addition of 1000 and 3000 FYT/kg phytase, but not by the addition of myo-inositol. Other plasma metabolites examined were not affected by dietary treatment. It can be concluded that oral delivery of myo-inositol results in rapid increase in plasma myo-inositol concentrations that peak approximately 45-60 min after feeding. Use of supplemental phytase achieves similar increases in myo-inositol concentration in plasma but the appearance is more gradual. Furthermore, supplementation of pig diets with exogenous phytase results in rapid appearance of P in plasma that may be sustained over time relative to diets with no added phytase.

  7. A concept analysis of turnover intention: implications for nursing management.

    Science.gov (United States)

    Takase, Miyuki

    2010-01-01

    This paper provides a review and concept analysis of turnover intention. The aim was to promote Nurse Managers' understanding of the meanings and mechanisms of turnover intention, which could help them counteract nurse turnover. Sixty-six papers published between January 1998 and August 2007 were collected from CINAHL, PubMed, and PsycINFO databases, and were subjected to Rogers' concept analysis. The results showed that turnover intention is a multi-stage process involving the voluntary departure of employees from their current position, and is triggered by negative psychological responses to internal/external job context. These psychological responses evolve into withdrawal cognition and behaviours, and lead to actual turnover. To prevent nurse turnover, Nurse Managers should closely observe the internal and external causes of turnover, and the stage of nurses' turnover intention.

  8. Staff turnover: occasional friend, frequent foe, and continuing frustration.

    Science.gov (United States)

    McConnell, C R

    1999-09-01

    Turnover appears to be a relatively simple concept. However, considerable confusion results when discussing turnover because of differences in how it is defined--what is counted, how it is counted, and how the rate of turnover is expressed. Turnover is also costly, although not enough attention is paid to turnover's cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some which can be corrected and some which cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role.

  9. Work-Related Variables and Turnover Intention among Registered Nurses.

    Science.gov (United States)

    Pooyan, Abdullah; And Others

    1990-01-01

    Health institutions have become more interested in the causes of job turnover among registered nurses. Proper management of job turnover can improve the financial health and long-term survival of health care institutions. (Author)

  10. PTH [parathyroid hormone] elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line

    International Nuclear Information System (INIS)

    Civitelli, R.; Reid, I.R.; Westbrook, S.; Avioli, L.V.; Hruska, K.A.

    1988-01-01

    Parathyroid hormone (PTH)-stimulated signal transduction through mechanisms alternate to adenosine 3',5'-cyclic monophosphate (cAMP) production were studied in UMR 106-01 cells, a cell line with an osteoblastic phenotype. PTH produced transient, dose-related increases in cytosolic calcium ([Ca 2+ ] i ), inositol trisphosphates, and diacylglycerol (DAG). Both inositol 1,4,5-trisphosphate (Ins-1,4,5P 3 ) and inositol 1,3,4-trisphosphate (Ins-1,3,4P 3 ) production were rapidly stimulated by PTH. Consistent with the production of Ins-1,3,4P 3 , rapid stimulation of late eluting inositol tetrakisphosphate was observed. The effects on the inositol phosphates were induced rapidly, consistent with roles as signals for changes in [Ca 2+ ] i . In saponin-permeabilized UMR 106-01 cells, Ins-1,4,5P 3 stimulated 45 Ca release from a nonmitochondrial intracellular pool. Thus the hypothesis that PTH-stimulated Ins-1,4,5P 3 production initiates Ca 2+ release and contributes to transient elevations of [Ca 2+ ] i is supported. These data suggest that stimulation of cAMP production during PTH stimulation may negatively affect production of rises in [Ca 2+ ] i during PTH stimulation. The inactivation of the inhibitory G protein of adenylate cyclase by pertussis toxin could explain its action similar to cAMP analogues. Cyclci nucleotides diminish the effects of PTH on [Ca 2+ ] i , probably interacting on a biochemical step subsequent to or independent of Ins-1,4,5P 3 release

  11. Inositol Depletion Induced by Acute Treatment of the Bipolar Disorder Drug Valproate Increases Levels of Phytosphingosine.

    Science.gov (United States)

    Jadhav, Shyamalagauri; Russo, Sarah; Cowart, L Ashley; Greenberg, Miriam L

    2017-03-24

    Bipolar disorder (BD) is a severe psychiatric illness affecting ∼1% of the world population. Valproate (VPA) and lithium, widely used for the treatment of BD, are not universally effective. These drugs have been shown to cause inositol depletion, but translating this observation to a specific therapeutic mechanism has been difficult, hampering the development of more effective therapies. We have shown previously in yeast that chronic VPA treatment induces the unfolded protein response due to increasing ceramide levels. To gain insight into the mechanisms activated during acute VPA treatment, we performed a genome-wide expression study in yeast treated with VPA for 30 min. We observed increased mRNA and protein levels of RSB1 , which encodes an exporter of long chain bases dihydrosphingosine (DHS) and phytosphingosine (PHS), and further saw that VPA increased sensitivity of an rsb1 Δ mutant to PHS, suggesting that VPA increases long chain base levels. Consistent with this, PHS levels were elevated in wild type and, to a greater extent, in rsb1 Δ cells. Expression of ORM genes (negative regulators of PHS synthesis) and of fatty acid elongase genes FEN1 and SUR4 were decreased, and expression of YOR1 (exporter of PHS-1P) and DPL1 (lyase that degrades DHS-1P and PHS-1P) was increased. These effects were more pronounced in medium lacking inositol, and were mirrored by inositol starvation of an ino1 Δ mutant. These findings provide a metabolic explanation as to how VPA-mediated inositol depletion causes increased synthesis of PHS and further support the therapeutic relevance of inositol depletion as a bipolar disorder treatment. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Formation and metabolism of inositol 1,4,5 trisphosphate in human platelets

    International Nuclear Information System (INIS)

    Daniel, J.L.; Dangelmaier, C.A.; Smith, J.B.

    1987-01-01

    [ 3 H]Myo-inositol (1,4,5)trisphosphate ((1,4,5)IP 3 ), when added to lysed platelets, was rapidly converted to [ 3 H]inositol (1,3,4,5)tetrakisphosphate which was in turn converted to [ 3 H]inositol (1,3,4)trisphosphate. This result demonstrates that platelets have the same metabolic pathways for interconversion of inositol polyphosphates that are found in other cells. Labelling of platelets with [ 32 P]orthophosphate, followed by h.1.p.c. was used to measure thrombin-induced changes in the three inositol polyphosphates. Interfering compounds were removed by a combination of enzymatic and nonenzymatic techniques. [ 32 P]-(1,4,5)IP 3 was formed rapidly and reached its maximal level at about 4 sec. It was also rapidly degraded and was no longer detectable after 30-60 sec. Formation of (1,3,4,5)IP 4 was almost as rapid as that of (1,4,5)IP 3 and remained at detectable levels for a longer time. (1,3,4)IP 3 was formed after an initial lag and this isomer reached its maximal level that was ten-fold higher than that of (1,4,5)IP 3 at 30 sec. Comparison of the intracellular Ca 2+ concentration as measured with fura-2 indicates that agents other than (1,4,5)IP 3 are responsible for the sustained maintenance of a high level of intracellular Ca 2+ . It is proposed that either (1,3,4)IP 3 or (1,3,4,5)IP 4 may also be Ca 2+ -mobilizing agents

  13. Inositol Depletion Induced by Acute Treatment of the Bipolar Disorder Drug Valproate Increases Levels of Phytosphingosine*

    Science.gov (United States)

    Jadhav, Shyamalagauri; Russo, Sarah; Cowart, L. Ashley; Greenberg, Miriam L.

    2017-01-01

    Bipolar disorder (BD) is a severe psychiatric illness affecting ∼1% of the world population. Valproate (VPA) and lithium, widely used for the treatment of BD, are not universally effective. These drugs have been shown to cause inositol depletion, but translating this observation to a specific therapeutic mechanism has been difficult, hampering the development of more effective therapies. We have shown previously in yeast that chronic VPA treatment induces the unfolded protein response due to increasing ceramide levels. To gain insight into the mechanisms activated during acute VPA treatment, we performed a genome-wide expression study in yeast treated with VPA for 30 min. We observed increased mRNA and protein levels of RSB1, which encodes an exporter of long chain bases dihydrosphingosine (DHS) and phytosphingosine (PHS), and further saw that VPA increased sensitivity of an rsb1Δ mutant to PHS, suggesting that VPA increases long chain base levels. Consistent with this, PHS levels were elevated in wild type and, to a greater extent, in rsb1Δ cells. Expression of ORM genes (negative regulators of PHS synthesis) and of fatty acid elongase genes FEN1 and SUR4 were decreased, and expression of YOR1 (exporter of PHS-1P) and DPL1 (lyase that degrades DHS-1P and PHS-1P) was increased. These effects were more pronounced in medium lacking inositol, and were mirrored by inositol starvation of an ino1Δ mutant. These findings provide a metabolic explanation as to how VPA-mediated inositol depletion causes increased synthesis of PHS and further support the therapeutic relevance of inositol depletion as a bipolar disorder treatment. PMID:28100786

  14. Autophagy, lipophagy and lysosomal lipid storage disorders.

    Science.gov (United States)

    Ward, Carl; Martinez-Lopez, Nuria; Otten, Elsje G; Carroll, Bernadette; Maetzel, Dorothea; Singh, Rajat; Sarkar, Sovan; Korolchuk, Viktor I

    2016-04-01

    Autophagy is a catabolic process with an essential function in the maintenance of cellular and tissue homeostasis. It is primarily recognised for its role in the degradation of dysfunctional proteins and unwanted organelles, however in recent years the range of autophagy substrates has also been extended to lipids. Degradation of lipids via autophagy is termed lipophagy. The ability of autophagy to contribute to the maintenance of lipo-homeostasis becomes particularly relevant in the context of genetic lysosomal storage disorders where perturbations of autophagic flux have been suggested to contribute to the disease aetiology. Here we review recent discoveries of the molecular mechanisms mediating lipid turnover by the autophagy pathways. We further focus on the relevance of autophagy, and specifically lipophagy, to the disease mechanisms. Moreover, autophagy is also discussed as a potential therapeutic target in several key lysosomal storage disorders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Synthesis and conformational analysis of a simplified inositol-model of the Streptococcus pneumoniae 19F capsular polysaccharide repeating unit.

    Science.gov (United States)

    Catelani, Giorgio; D'Andrea, Felicia; Guazzelli, Lorenzo; Griselli, Alessio; Testi, Nicola; Chiacchio, Maria Assunta; Legnani, Laura; Toma, Lucio

    2017-04-18

    Carbohydrate mimics have been studied for a long time as useful sugar substitutes, both in the investigation of biological events and in the treatment of sugar-related diseases. Here we report further evaluation of the capabilities of inositols as carbohydrate substitutes. The conformational features of an inositol-model of a simplified repeating unit corresponding to the capsular polysaccharide of Streptococcus pneumoniae 19F has been evaluated by computational analysis, and compared to the native repeating unit. The inositol mimic was synthesized, and its experimental spectroscopic data allowed for verification of the theoretical results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Salary and Ranking and Teacher Turnover: A Statewide Study

    Science.gov (United States)

    Garcia, Cynthia Martinez; Slate, John R.; Delgado, Carmen Tejeda

    2009-01-01

    This study examined three years of data obtained from the Academic Excellence Indicator System of the State of Texas regarding teacher turnover rate and teacher salary. Across all public school districts, teacher salary was consistently negatively related to teacher turnover; that is, where salary was lower, turnover rate was higher When data were…

  17. Inositol in preterm infants at risk for or having respiratory distress syndrome.

    Science.gov (United States)

    Howlett, Alexandra; Ohlsson, Arne; Plakkal, Nishad

    2015-02-04

    Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes. The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov and Controlled-trials.com were searched in September 2014. The reference lists of identified randomised controlled trials (RCTs), personal files and Web of Science were searched. All RCTs of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention were included. Outcomes of interest were neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis. Data on neonatal outcomes were abstracted independently by the three review authors and any discrepancy was resolved through consensus. Outcomes were reported as relative risk (RR), risk difference (RD) and number needed to treat to benefit (NNTB) or to harm (NNTH). Four published RCTs and one ongoing RCT were identified. Study quality varied and interim analyses had occurred in all trials of repeat doses of inositol that provided data for the outcomes of interest in this review. In these trials neonatal death was found to be significantly reduced (3 trials, 355 neonates; typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.17 to -0.03; NNTB 11, 95% CI 6 to 33). Infant deaths were reduced (3 trials, 355 infants; typical RR 0.55, 95% CI 0.40 to 0.77; typical RD -0.18, 95% CI -0.27 to -0.08; NNTB 6, 95% CI 4 to 13). ROP stage ≥ 3 was significantly reduced (2 trials, 262 infants; typical RR 0.09, 95% CI 0.01 to 0

  18. Seed lipids.

    Science.gov (United States)

    Wolff, I A

    1966-12-02

    Many of the newly discovered seedoil acids have reactive or unusual functional groups or other facets of molecular structure that permit their ready differentiation from oleic, linoleic, linolenic, and the other most prevalent saturated and unsaturated long-chain fatty acids. The recognition and availability of the new acids, coupled with methods that make detection and determination easy, will help studies of lipid biosynthesis in the plant and of lipid metabolism and utilization in animals, and will stimulate more studies in depth on the fine points of seedlipid structure. Correlations of structural patterns in seed lipids of particular groups of plants with classical taxonomic categories will permit clarifications, raise needed questions concerning classifications, and accelerate research in chemotaxonomy and phylogenetics. Seed lipids are particularly well suited for establishing relationships among plants because of their great variety in structure compared to the more limited structural types of amino acids, sugars, purines, and many other plant substances. The newly characterized seed oils are potentially important industrial raw materials whenever they come from agronomically promising plant species. The molecular structures of seed triglycerides have major influence on their physical properties and therefore advances in knowledge in that sphere have practical implications. For example, the unusual characteristics of cocoa butter that make it so valuable for food and confectionery use are attributed to the specific arrangement of fatty acids it its triglycerides. The glycerides are almost all 2-oleic-1,3-disaturated acid triglycerides. The physical characteristics of lard are advantageously changed by catalytically rearranging fatty acyl groups among the glycerides initially in the fat to achieve a more nearly random distribution, followed sometimes by further fractionation to remove more saturated glycerides. Through this change of glyceride structures a

  19. Antigen receptor-mediated regulation of sustained polyphosphoinositide turnover in a human T cell line. Evidence for a receptor-regulated pathway for production of phosphatidylinositol 4,5-bisphosphate

    International Nuclear Information System (INIS)

    Inokuchi, S.; Imboden, J.B.

    1990-01-01

    Stimulation of the human T cell line, Jurkat, by the addition of monoclonal antibodies reactive with the T cell antigen receptor complex (CD3/Ti) leads to sustained increases in levels of inositol 1,4,5-trisphosphate. To investigate the possibility that the production of polyphosphoinositides is regulated during CD3/Ti stimulation, we studied Jurkat cells whose inositol phospholipids had been labeled to steady state with [3H]inositol, as well as Jurkat cells during nonequilibrium labeling with [32P]orthophosphate. The addition of CD3 monoclonal antibodies led to a 4-5-fold increase in [3H]inositol trisphosphate that was sustained for greater than 20 min. Within 60 s of CD3/Ti stimulation, [3H] phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and [3H]phosphatidylinositol 4-phosphate (PtdIns4P) decreased by 65 and 35%, respectively. This change in [3H]PtdIns(4,5)P2 persisted for greater than 20 min. The decrease in [3H]PtdIns4P, however, was transient, and, after 5 min, the levels of [3H]PtdIns4P were comparable in stimulated and unstimulated cells. To examine the rate of flux through inositol phospholipids, we measured the CD3/Ti-stimulated changes in the ratio, 32P cpm/3H cpm, in each inositol phospholipid. CD3/Ti stimulation led to accelerated fluxes through PtdIns(4,5)P2 and phosphatidylinositol (PtdIns) that were maintained for greater than 20 min. After the initial 30 s, however, there was no detectable effect of anti-CD3 on flux through Ptsins4p. This observation suggested that, during CD3/Ti stimulation, production of PtdIns(4,5)P2 from PtdIns might occur via a small pool of PtdIns4P with a very high turnover. The existence of such a pool was established by determining that, in stimulated cells, the 32P-specific activity of the 1-position phosphate of PtdIns(4,5)P2 was 8-10-fold that of PtdIns4P

  20. Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens

    International Nuclear Information System (INIS)

    Singh, Nisha; Halliday, Amy C.; Knight, Matthew; Lack, Nathan A.; Lowe, Edward; Churchill, Grant C.

    2012-01-01

    M. musculus and H. sapiens inositol monophosphatase 1 were cloned, expressed, purified and crystallized. Diffraction data were collected and analysed at resolutions of 2.4 and 1.7 Å, respectively, and the structures were compared in order to identify any structural differences. Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method. The structures were solved at resolutions of 2.4 and 1.7 Å, respectively. Comparison of MmIMPase 1 and HsIMPase 1 revealed a core r.m.s. deviation of 0.516 Å

  1. Determination of Myo-Inositol in Infant, Pediatric, and Adult Formulas by Liquid Chromatography-Pulsed Amperometric Detection with Column Switching: Collaborative Study, Final Action 2011.18.

    Science.gov (United States)

    Butler-Thompson, Linda D; Jacobs, Wesley A; Schimpf, Karen J

    2015-01-01

    AOAC First Action Method 2011.18, Myo-Inositol (Free and Bound as Phosphatidylinositol) in Infant and Pediatric Formulas and Adult Nutritionals, was collaboratively studied. With this method free myo-inositol and phosphatidylinositol bound myo-inositol are extracted using two different sample preparation procedures, separated by ion chromatography using a combination of Dionex Carbo Pac PA1 and MA1 columns with column switching, and detected with pulsed amperometry using a gold electrode. Free myo-inositol is extracted from samples with dilute hydrochloric acid and water. Phosphatidylinositol is extracted from samples with chloroform and separated from other fats with silica SPE cartridges. Myo-inositol is then released from the glycerol backbone with concentrated acetic and hydrochloric acids at 120°C. During this collaborative study, nine laboratories from five different countries analyzed blind duplicates of nine infant and pediatric nutritional formulas for both free and phosphatidylinositol bound myo-inositol, and one additional laboratory only completed the free myo-inositol analyses. The method demonstrated acceptable repeatability and reproducibility and met the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) Standard Method Performance Requirements (SMPRs®) for free myo-inositol plus phosphatidylinositol bound myo-inositol for all the matrixes analyzed. SMPRs for repeatability were ≤5% RSD at myo-inositol concentrations of 2-68 mg/100 g ready-to-feed (RTF) liquid. SMPRs for reproducibility were ≤8% RSD in products with myo-inositol concentrations ranging from 2 to 68 mg/100 g RTF liquid. During this collaborative study, repeatability RSDs ranged from 0.51 to 3.22%, and RSDs ranged from 2.66 to 7.55% for free myo-inositol plus phosphatidylinositol bound myo-inositol.

  2. How Wage Compression Affects Job Turnover

    OpenAIRE

    Heyman, Fredrik

    2008-01-01

    I use Swedish establishment-level panel data to test Bertola and Rogerson’s (1997) hypothesis of a positive relation between the degree of wage compression and job reallocation. Results indicate that the effect of wage compression on job turnover is positive and significant in the manufacturing sector. The wage compression effect is stronger on job destruction than on job creation, consistent with downward wage rigidity. Further results include a strong positive relationship between the fract...

  3. Employee turnover, HRM and institutional contexts.

    OpenAIRE

    Croucher, Richard; Wood, Geoffrey; Brewster, Chris; Brookes, Michael

    2012-01-01

    Literature on comparative capitalism remains divided between approaches founded on stylized case study evidence and descriptions of broad trends, and those that focus on macro data. In contrast, this study explores the relevance of Amable’s approach to understanding differences in employment relations practice, based on firm-level micro data. The article examines employee–employer interdependence (including turnover rates) in different categories of economy as classified by Amable. The findin...

  4. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C

    1993-01-01

    in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  5. High bone turnover in Irish professional jockeys.

    LENUS (Irish Health Repository)

    Waldron-Lynch, F

    2012-02-01

    SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +\\/- 1.7 kg\\/m(2); previous fracture frequency was 3.2 +\\/- 2.0 per rider. All had normal endocrine axes. The jockeys\\' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.

  6. Ca2+-mediated generation of inositol 1,4,5-triphosphate and inositol 1,3,4,5-tetrakisphosphate in pancreatic islets. Studies with K+, glucose, and carbamylcholine

    International Nuclear Information System (INIS)

    Biden, T.J.; Peter-Riesch, B.; Schlegel, W.; Wollheim, C.B.

    1987-01-01

    The role of Ca2+ in the generation of inositol phosphates was investigated using rat pancreatic islets after steady state labeling with myo-[2- 3 H]inositol. Depolarizing K+ concentrations (24 mM) evoked early (2 s) increases in inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4) as measured by high performance anion-exchange chromatography. The increase in Ins-1,4,5-P3 was transient and was followed by a more pronounced rise in Ins-1,3,4-P3. These effects were dependent on the presence of extracellular Ca2+ but were not secondary to release of either neurotransmitters or metabolites of arachidonic acid. K+ also promoted the breakdown of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) and of the other phosphoinositides. Glucose (16.7 mM) was less marked in its effects but still promoted rapid increases in Ins-1,3,4,5-P4 (2 s) and Ins-1,4,5-P3 (10 s) and a slower rise in Ins-1,3,4-P3 (30 s). The levels of all three metabolites rose steadily over 10 min stimulation. These responses to glucose could be largely, although not entirely, inhibited by depletion of extracellular Ca2+ or by Ca2+ channel blockade with verapamil (20 microM). Carbamylcholine (0.5 mM) was the most potent stimulus used evoking early rises in Ins-1,4,5-P3 and Ins-1,3,4,5-P4 (2 s) followed by Ins-1,3,4-P3 (10 s), effects which were only partially dependent on extracellular Ca2+. The results suggest that a Ca2+-mediated PtdIns-4,5-P2 hydrolysis accounts for most of the Ins-1,4,5-P3 generated in response to glucose but not carbamylcholine

  7. PERAN STRES KERJA DAN KEPUASAN KERJA UNTUK MENGURANGI TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Syarifah Nazenin

    2014-09-01

    Full Text Available Tujuan penelitian ini untuk menguji pengaruh variabel stres kerja dan kepuasan kerja pada turnover intention karyawan tetap bagian produksi. Sampel penelitian ini adalah 86 responden, menggunakan metode Slovin dengan teknik probability sampling dengan jenis proportionate random sampling. Berdasarkan hasil penelitian, menunjukkan bahwa stres kerja berpengaruh positif signifikan pada turnover intention. Kemudian, kepuasan kerja berpengaruh negatif signifikan. Penelitian ini menyimpulkan, bahwa stres kerja berpengaruh positif dan signifikan pada turnover intention karyawan dan kepuasan kerja berpengaruh negatif dan signifikan terhadap turnover intention karyawan. Implikasi manajerial yang bisa dilakukan adalah dengan pengurangan tingkat stres karyawan dan membuat program untuk tujuan menekan turnover intention, seperti kesempatan promosi dan meningkatkan reward karyawan. The purpose of this study conducted to examine the effect of work stress and job satisfaction on turnover intention of employee in production department. The sample was 86 respondent, using Slovin method with proportionate random sampling technique. The result showed that job stress has a positive effect on turnover intention while job satisfaction has a negative effect on turnover intention. This study conclude that job stress has positive and significant impact on employee turnover intention and job satisfaction significantly and negatively related to turnover intention of employees. Therefore, it is recommended to managerial level people to reduce stress levels in employees and to create a program for pressing turnover intention, such as promotional opportunities and improve employee rewards.

  8. The RpiR-Like Repressor IolR Regulates Inositol Catabolism in Sinorhizobium meliloti▿†

    Science.gov (United States)

    Kohler, Petra R. A.; Choong, Ee-Leng; Rossbach, Silvia

    2011-01-01

    Sinorhizobium meliloti, the nitrogen-fixing symbiont of alfalfa, has the ability to catabolize myo-, scyllo-, and d-chiro-inositol. Functional inositol catabolism (iol) genes are required for growth on these inositol isomers, and they play a role during plant-bacterium interactions. The inositol catabolism genes comprise the chromosomally encoded iolA (mmsA) and the iolY(smc01163)RCDEB genes, as well as the idhA gene located on the pSymB plasmid. Reverse transcriptase assays showed that the iolYRCDEB genes are transcribed as one operon. The iol genes were weakly expressed without induction, but their expression was strongly induced by myo-inositol. The putative transcriptional regulator of the iol genes, IolR, belongs to the RpiR-like repressor family. Electrophoretic mobility shift assays demonstrated that IolR recognized a conserved palindromic sequence (5′-GGAA-N6-TTCC-3′) in the upstream regions of the idhA, iolY, iolR, and iolC genes. Complementation assays found IolR to be required for the repression of its own gene and for the downregulation of the idhA-encoded myo-inositol dehydrogenase activity in the presence and absence of inositol. Further expression studies indicated that the late pathway intermediate 2-keto-5-deoxy-d-gluconic acid 6-phosphate (KDGP) functions as the true inducer of the iol genes. The iolA (mmsA) gene encoding methylmalonate semialdehyde dehydrogenase was not regulated by IolR. The S. meliloti iolA (mmsA) gene product seems to be involved in more than only the inositol catabolic pathway, since it was also found to be essential for valine catabolism, supporting its more recent annotation as mmsA. PMID:21784930

  9. Influence of orlistat on bone turnover and body composition

    DEFF Research Database (Denmark)

    Gotfredsen, A; Westergren Hendel, H; Andersen, T

    2001-01-01

    was the fU-OHpr/creat ratio, which increased from 12.0 to 20.1 in the OLS group but only from 10.9 to 1 3.2 in the placebo group. CONCLUSION: One year's treatment with OLS induces a lipid malabsorption which enhances a dietary weight loss without any significant deleterious effects on body composition. OLS......OBJECTIVE: To investigate the influence of the pancreas lipase inhibitor orlistat (OLS) on calcium metabolism, bone turnover, bone mass, bone density and body composition when given for obesity as adjuvant to an energy- and fat-restricted diet. DESIGN: Randomized controlled double-blinded trial...... of treatment with OLS 120 mg three times daily or placebo for 1 y. SUBJECTS: Thirty obese subjects with a mean body mass index (BMI) of 36.9+/-3.7 kg/m(2) and a mean age of 41+/-11 y. Sixteen patients were assigned to OLS and 14 to placebo. MEASUREMENTS: Dual energy X-ray absorptiometry (DXA) measurements...

  10. myo-Inositol synthesis from [1-3H]glucose in Phaseolus vulgaris L. during early stages of germination

    International Nuclear Information System (INIS)

    Sasaki, K.; Taylor, I.E.P.

    1986-01-01

    Radiolabeled D-[1- 3 H]glucose was fed by imbibition under sterile conditions to bean (Phaseolus vulgaris L.) seeds. After 72 and 96 hours of feeding, the 3 H was located in uronic acid and pentose residues as well as hexose residues of cell wall polysaccharides in growing hypocotyl and root. Free myo-inositol present in cotyledons, hypocotyl, and root also contained 3 H, showing that de novo synthesis of myo-inositol from [1- 3 H]glucose did occur during the first 72 hours of germination. More than 90% of the labeled, free myo-inositol was present in the cotyledons. The 3 H percentage in trifluoroacetic acid-soluble arabinaose residues of cell wall polysaccharides from 72-hour-old bean hypocotyls was only half of their mole percentage. On the other hand, 3 H percentages in hexose residues were higher than their mole percentages. The results suggest that myo-inositol is synthesized from reserve sugars during the very early stages of germination, and that the newly synthesized myo-inositol, as well as that stored in cotyledons, can be used for the construction of new hypocotyl and root cell wall polysaccharides after conversion into uronic acids and pentoses via the myo-inositol oxidation pathway

  11. Synthesis and preliminary in vivo evaluation of new [18F]fluoro-inositols as Positron Emission Tomography radiotracers.

    Science.gov (United States)

    Collet, Charlotte; Schmitt, Sébastien; Maskali, Fatiha; Clément, Alexandra; Chrétien, Françoise; Karcher, Gilles; Marie, Pierre-Yves; Poussier, Sylvain; Lamandé-Langle, Sandrine

    2017-10-15

    This study describes the synthesis and radiosynthesis of eight new [ 18 F]fluoro-inositol-based radiotracers in myo- and scyllo-inositol configuration. These radiotracers are equipped with a propyl linker bearing fluorine-18. This fluorinated arm is either on a hydroxyl group, i.e. O-alkylated inositols, or on the cyclohexyl backbone, i.e. C-branched derivatives. To modulate lipophilicity, inositols were synthesized in acetylated or hydroxylated form. Automated radiosynthesis was performed on the AllInOne module and the radiotracers were produced in good radiochemical yields (15-31.5% dc). Preliminary in vivo preclinical evaluation of these eight [ 18 F]fluoro-inositols as Positron Emission Tomography (PET) imaging agents in a breast tumour-bearing mouse model was performed and compared with [ 18 F]-2-fluoro-2-deoxy-d-glucose ([ 18 F]FDG). Amongst the different inositols, [ 18 F]myo-2 showed the highest tumour uptake 2.34±0.39%ID/g, revealing the potential of this tracer for monitoring breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Pharmacokinetics and Safety of a Single Intravenous Dose of myo-Inositol in Preterm Infants of 23 to 29 weeks

    Science.gov (United States)

    Phelps, Dale L.; Ward, Robert M.; Williams, Rick L.; Watterberg, Kristi L.; Laptook, Abbot R.; Wrage, Lisa A.; Nolen, Tracy L.; Fennell, Timothy R.; Ehrenkranz, Richard A.; Poindexter, Brenda B.; Cotten, C. Michael; Hallman, Mikko K.; Frantz, Ivan D.; Faix, Roger G.; Zaterka-Baxter, Kristin M.; Das, Abhik; Ball, M. Bethany; O’Shea, T. Michael; Lacy, Conra Backstrom; Walsh, Michele C.; Shankaran, Seetha; Sánchez, Pablo J.; Bell, Edward F.; Higgins, Rosemary D.

    2014-01-01

    Background Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia (BPD) and reduced severe retinopathy of prematurity (ROP) in 2 randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed prior to efficacy trials. Methods Infants of 23–29 weeks gestation were randomized to a single intravenous (IV) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed effects approach. Safety outcomes were recorded. Results A 1-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age (GA) strata and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance 0.0679 l/kg/h, endogenous production 2.67 mg/kg/h and the half life 5.22 h when modeled without the covariates. During the first 12 h renal inositol excretion quadrupled in the 120 mg/kg group, returning to near baseline after 48 h. There was no diuretic side-effect. No significant differences in adverse events occurred between the 3 groups (p > 0.05). Conclusions A single compartment model accounting for endogenous production satisfactorily described the PK of IV inositol. PMID:24067395

  13. NATURE OF THE LIPIDS OF SOME LACTIC ACID BACTERIA1

    Science.gov (United States)

    Ikawa, Miyoshi

    1963-01-01

    Ikawa, Miyoshi (University of California, Berkeley). Nature of the lipids of some lactic acid bacteria. J. Bacteriol. 85:772–781. 1963.—Lactobacillus casei, L. plantarum, Leuconostoc mesenteroides, Pediococcus cerevisiae, and Streptococcus faecalis were grown on a lipid-free medium, and the amounts of acetone-soluble lipids, acetone-insoluble phospholipids, and unextracted or bound lipid in the cells were estimated. Neutral glycerides appeared to be absent, or present only in traces, in L. casei and S. faecalis. L. plantarum, L. mesenteroides, and P. cerevisiae, in addition to containing glycerides, appeared to contain glycolipids of glucose and galactose. Glycerol was present in the phospholipid fraction of all the organisms, and, in addition, galactose was present in L. mesenteroides. Paper chromatography of hydrolysates of the phospholipid fractions showed the absence of the usual phospholipid nitrogen bases, serine, ethanolamine, and choline, in these organisms. Microbiological assays of lyophilized unextracted cells for myo-inositol and choline also showed that lipids containing these components occurred in very small amounts at most. The principal ninhydrin-reacting substance in the phospholipid fraction of L. casei, L. plantarum, P. cerevisiae, and S. faecalis was lysine, which seemed to be exclusively of the l configuration. The principal ninhydrin-reacting substance in the L. mesenteroides phospholipid fraction was d-alanine. These amino acids appeared to be bound in components of the phospholipid fraction and not free. Images PMID:14044942

  14. Treatment staff turnover in organizations implementing evidence-based practices: turnover rates and their association with client outcomes.

    Science.gov (United States)

    Garner, Bryan R; Hunter, Brooke D; Modisette, Kathryn C; Ihnes, Pamela C; Godley, Susan H

    2012-03-01

    High staff turnover has been described as a problem for the substance use disorder treatment field. This assertion is based primarily on the assumption that staff turnover adversely impacts treatment delivery and effectiveness. This assumption, however, has not been empirically tested. In this study, we computed annualized rates of turnover for treatment staff (N = 249) participating in an evidence-based practice implementation initiative and examined the association between organizational-level rates of staff turnover and client-level outcomes. Annualized rates of staff turnover were 31% for clinicians and 19% for clinical supervisors. In addition, multilevel analyses did not reveal the expected relationship between staff turnover and poorer client-level outcomes. Rather, organizational-level rates of staff turnover were found to have a significant positive association with two measures of treatment effectiveness: less involvement in illegal activity and lower social risk. Possible explanations for these findings are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. An Uncharacterized Member of the Ribokinase Family in Thermococcus kodakarensis Exhibits myo-Inositol Kinase Activity*

    Science.gov (United States)

    Sato, Takaaki; Fujihashi, Masahiro; Miyamoto, Yukika; Kuwata, Keiko; Kusaka, Eriko; Fujita, Haruo; Miki, Kunio; Atomi, Haruyuki

    2013-01-01

    Here we performed structural and biochemical analyses on the TK2285 gene product, an uncharacterized protein annotated as a member of the ribokinase family, from the hyperthermophilic archaeon Thermococcus kodakarensis. The three-dimensional structure of the TK2285 protein resembled those of previously characterized members of the ribokinase family including ribokinase, adenosine kinase, and phosphofructokinase. Conserved residues characteristic of this protein family were located in a cleft of the TK2285 protein as in other members whose structures have been determined. We thus examined the kinase activity of the TK2285 protein toward various sugars recognized by well characterized ribokinase family members. Although activity with sugar phosphates and nucleosides was not detected, kinase activity was observed toward d-allose, d-lyxose, d-tagatose, d-talose, d-xylose, and d-xylulose. Kinetic analyses with the six sugar substrates revealed high Km values, suggesting that they were not the true physiological substrates. By examining activity toward amino sugars, sugar alcohols, and disaccharides, we found that the TK2285 protein exhibited prominent kinase activity toward myo-inositol. Kinetic analyses with myo-inositol revealed a greater kcat and much lower Km value than those obtained with the monosaccharides, resulting in over a 2,000-fold increase in kcat/Km values. TK2285 homologs are distributed among members of Thermococcales, and in most species, the gene is positioned close to a myo-inositol monophosphate synthase gene. Our results suggest the presence of a novel subfamily of the ribokinase family whose members are present in Archaea and recognize myo-inositol as a substrate. PMID:23737529

  16. Salinity-induced regulation of the myo-inositol biosynthesis pathway in tilapia gill epithelium

    Science.gov (United States)

    Sacchi, Romina; Li, Johnathon; Villarreal, Fernando; Gardell, Alison M.; Kültz, Dietmar

    2013-01-01

    SUMMARY The myo-inositol biosynthesis (MIB) pathway converts glucose-6-phosphate to the compatible osmolyte myo-inositol that protects cells from osmotic stress. Using proteomics, the enzymes that constitute the MIB pathway, myo-inositol phosphate synthase (MIPS) and inositol monophosphatase 1 (IMPA1), are identified in tilapia (Oreochromis mossambicus) gill epithelium. Targeted, quantitative, label-free proteomics reveals that they are both upregulated during salinity stress. Upregulation is stronger when fish are exposed to severe (34 ppt acute and 90 ppt gradual) relative to moderate (70 ppt gradual) salinity stress. IMPA1 always responds more strongly than MIPS, suggesting that MIPS is more stable during salinity stress. MIPS is N-terminally acetylated and the corresponding peptide increases proportionally to MIPS protein, while non-acetylated N-terminal peptide is not detectable, indicating that MIPS acetylation is constitutive and may serve to stabilize the protein. Hyperosmotic induction of MIPS and IMPA1 is confirmed using western blot and real-time qPCR and is much higher at the mRNA than at the protein level. Two distinct MIPS mRNA variants are expressed in the gill, but one is more strongly regulated by salinity than the other. A single MIPS gene is encoded in the tilapia genome whereas the zebrafish genome lacks MIPS entirely. The genome of euryhaline tilapia contains four IMPA genes, two of which are expressed, but only one is salinity regulated in gill epithelium. The genome of stenohaline zebrafish contains a single IMPA gene. We conclude that the MIB pathway represents a major salinity stress coping mechanism that is regulated at multiple levels in euryhaline fish but absent in stenohaline zebrafish. PMID:24072791

  17. A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women

    Directory of Open Access Journals (Sweden)

    Elena Benelli

    2016-01-01

    Full Text Available Introduction. We evaluated the effects of a therapy that combines myo-inositol (MI and D-chiro-inositol (DCI in young overweight women affected by polycystic ovary syndrome (PCOS, characterized by oligo- or anovulation and hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46 patients affected by PCOS and, randomly, we assigned them to two groups, A and B, treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or with placebo (folic acid for six months. Thus, we analyzed pretreatment and posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin, androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index, and fasting glucose and insulin. Results. We recorded a statistically significant reduction of LH, free testosterone, fasting insulin, and HOMA index only in the group treated with the combined therapy of MI plus DCI; in the same patients, we observed a statistically significant increase of 17-beta-Estradiol levels. Conclusions. The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women.

  18. Urinary Excretion of Myo-Inositol and D-Chiro-Inositol in Early Pregnancy Is Enhanced in Gravidas With Gestational Diabetes Mellitus.

    Science.gov (United States)

    Murphy, Aisling; Shamshirsaz, Amir; Markovic, Daniela; Ostlund, Richard; Koos, Brian

    2016-03-01

    The effects of gestational diabetes mellitus (GDM) were determined on urinary excretion of putative components of insulin signaling. Random urine samples were collected from 375 gravidas at 6 to 14 weeks' gestation, 22 to 32 weeks' gestation, and ∼6 weeks' postpartum. Gestational diabetes mellitus developed in 35 women who were matched with 59 normal gravidas. Urinary concentrations of myo-inositol (MI) and D-chiro-inositol (DCI) were measured by gas chromatography/mass spectrometry and normalized to creatinine levels. Compared to postpartum values, urinary excretion of MI and DCI was increased 2.9-fold and 2-fold, respectively, in early pregnancy, and 5.5-fold and 4.5-fold, respectively, in later gestation. Gravidas with GDM had significantly greater MI and DCI excretion than controls in the first trimester but not subsequently. The results suggest that gravidas destined to develop GDM have altered synthesis, metabolism, and/or renal excretion of MI and DCI in early pregnancy. © The Author(s) 2015.

  19. α-Synuclein aggregation, seeding and inhibition by scyllo-inositol

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Tarek [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada); McLaurin, JoAnne, E-mail: jmclaurin@sri.utoronto.ca [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada)

    2016-01-15

    Recent literature demonstrates the accelerated aggregation of α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease (PD), by the presence of preformed fibrillar conformers in vitro. Furthermore, these preformed fibrillar seeds are suggested to accelerate pathological induction in vivo when injected into the brains of mice. Variation in the results of in vivo studies is proposed to be caused by α-synuclein conformational variants. To investigate the impact of amino acid sequence on seeding efficiency, human and mouse α-synuclein seeds, which vary at 7 amino acid residues, were generated and cross-seeding kinetics studied. Using transmission electron microscopy (TEM), we confirmed that mouse α-synuclein aggregated more rapidly than human α-synuclein. Subsequently, we determined that seeding of human and mouse α-synuclein was more rapid in the presence of seeds generated from the same species. In addition, an established amyloid inhibitor, scyllo-inositol, was examined for potential inhibitory effects on α-synuclein aggregation. TEM analysis of protein:inhibitor assays demonstrated that scyllo-inositol inhibits the aggregation of α-synuclein, suggesting the therapeutic potential of the small molecule in PD. - Highlights: • Mouse α-syn fibrillizes in a significantly shorter timeframe than human α-syn. • Seeding of monomers is more efficient when seeds originate from the same species. • scyllo-Inositol has anti-aggregation effects on mouse and human α-syn.

  20. Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tartaglio, Virginia [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Rennie, Emilie A. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Cahoon, Rebecca [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Baidoo, Edward [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mortimer, Jennifer C. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Cahoon, Edgar B. [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Scheller, Henrik V. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    2016-09-19

    Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss-of-function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen-specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid-mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short-chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. In conclusion, this study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important role s for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.

  1. Hydrogen peroxide production and myo-inositol metabolism as important traits for virulence of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Ferrarini, M G; Mucha, S G; Parrot, D; Meiffren, G; Bachega, J F R; Comte, G; Zaha, A; Sagot, M F

    2018-04-06

    Mycoplasma hyopneumoniae is the causative agent of enzootic pneumonia. In our previous work, we reconstructed the metabolic models of this species along with two other mycoplasmas from the respiratory tract of swine: Mycoplasma hyorhinis, considered less pathogenic but which nonetheless causes disease and Mycoplasma flocculare, a commensal bacterium. We identified metabolic differences that partially explained their different levels of pathogenicity. One important trait was the production of hydrogen peroxide from the glycerol metabolism only in the pathogenic species. Another important feature was a pathway for the metabolism of myo-inositol in M. hyopneumoniae. Here, we tested these traits to understand their relation to the different levels of pathogenicity, comparing not only the species but also pathogenic and attenuated strains of M. hyopneumoniae. Regarding the myo-inositol metabolism, we show that only M. hyopneumoniae assimilated this carbohydrate and remained viable when myo-inositol was the primary energy source. Strikingly, only the two pathogenic strains of M. hyopneumoniae produced hydrogen peroxide in complex medium. We also show that this production was dependent on the presence of glycerol. Although further functional tests are needed, we present in this work two interesting metabolic traits of M. hyopneumoniae that might be directly related to its enhanced virulence. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  2. Isolation and Identification of Myo-Inositol Crystals from Dragon Fruit (Hylocereus polyrhizus

    Directory of Open Access Journals (Sweden)

    Chandran Somasundram

    2012-04-01

    Full Text Available Crystals isolated from Hylocereus polyrhizus were analyzed using four different approaches—X-ray Crystallography, High Performance Liquid Chromatography (HPLC, Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS and Nuclear Magnetic Resonance (NMR and identified as myo-inositol. The X-ray crystallography analysis showed that the unit-cell parameters were: a = 6.6226 (3 Å, b = 12.0462 (5 Å, c = 18.8942 (8 Å, α = 90.00, β = 93.98, δ = 90.00. The purity of the crystals were checked using HPLC, whereupon a clean single peak was obtained at 4.8 min with a peak area of 41232 μV*s. The LC-MS/MS technique, which is highly sensitive and selective, was used to provide a comparison of the isolated crystals with a myo-inositol standard where the results gave an identical match for both precursor and product ions. NMR was employed to confirm the molecular structure and conformation of the crystals, and the results were in agreement with the earlier results in this study. The discovery of myo-inositol crystals in substantial amount in H. polyrhizus has thus far not been reported and this is an important finding which will increase the marketability and importance of H. polyrhizus as a crop with a wide array of health properties.

  3. Characterization of a Saccharomyces cerevisiae mutant defective in inositol sphingolipid synthesis

    International Nuclear Information System (INIS)

    Pinto, W.J.; Wells, G.B.; Williams, A.C.; Anderson, K.A.; Teater, E.C.; Lester, R.L.

    1986-01-01

    A mutant of S. cerevisiae, auxotrophic for the sphingolipid long chain bases sphinganine or 4-hydroxysphinganine has been further characterized. The mutant is defective in the first step in the synthesis of sphingolipid long chain bases, the formation of 3-keto-sphinganine from palmitoyl CoA and L-serine. Crude membranes from wild type cells exhibit a palmitoyl CoA dependent conversion of [ 3 H]serine to a labeled product with the properties of 3-ketosphinganine, whereas membranes from the mutant exhibit negligible activity. As expected from this result, they authors find that 3-ketosphinganine supports growth of the mutant as effectively as erythro-sphinganine. To study the sequelae of long chain base deprivation in the mutant required a method to effectively remove lipophilic long chain bases from the cultured cells. They have found that addition of α-cyclodextrin to the culture medium evidently binds sphinganine tightly enough such that within an hour they observe inhibition of growth (turbidity, cell count) and incorporation of [ 3 H]inositol into sphingolipids. Such treatment also results in a loss of cell viability, a long chain base less death possibly similar to the inositol-less death observed in inositol auxotrophs of yeast

  4. Bacillus subtilis iolU encodes an additional NADP+-dependent scyllo-inositol dehydrogenase.

    Science.gov (United States)

    Kang, Dong-Min; Tanaka, Kosei; Takenaka, Shinji; Ishikawa, Shu; Yoshida, Ken-Ichi

    2017-05-01

    Bacillus subtilis genes iolG, iolW, iolX, ntdC, yfiI, yrbE, yteT, and yulF belong to the Gfo/Idh/MocA family. The functions of iolG, iolW, iolX, and ntdC are known; however, the functions of the others are unknown. We previously reported the B. subtilis cell factory simultaneously overexpressing iolG and iolW to achieve bioconversion of myo-inositol (MI) into scyllo-inositol (SI). YulF shares a significant similarity with IolW, the NADP + -dependent SI dehydrogenase. Transcriptional abundance of yulF did not correlate to that of iol genes involved in inositol metabolism. However, when yulF was overexpressed instead of iolW in the B. subtilis cell factory, SI was produced from MI, suggesting a similar function to iolW. In addition, we demonstrated that recombinant His 6 -tagged YulF converted scyllo-inosose into SI in an NADPH-dependent manner. We have thus identified yulF encoding an additional NADP + -dependent SI dehydrogenase, which we propose to rename iolU.

  5. Formation and actions of calcium-mobilizing messenger, inositol 1,4,5-trisphosphate

    International Nuclear Information System (INIS)

    Putney, J.W. Jr.

    1987-01-01

    A variety of surface membrane receptors can activate a phospholipase C, which degrades phosphatidylinositol 4,5-bisphosphate liberating a calcium mobilizing second messenger, inositol 1,4,5-trisphosphate [(1,4,5)IP 3 ]. The coupling of surface receptors to the phospholipase C involves one or more quanine nucleotide-dependent regulatory proteins that are similar but not identical to those that regulate adenylate cyclase. (1,4,5)IP 3 has been shown to release Ca 2+ from a portion of the endoplasmic reticulum and is believed responsible for the initial phase of Ca 2+ mobilization ascribed to internal Ca 2+ release. (1,4,5)IP 3 acts by binding to a specific receptor that either is a component of, or regulates, a Ca 2+ ion channel. The release of Ca 2+ from the (1,4,5)IP 3 -sensitive component of the endoplasmic reticulum may secondarily activate the second phase of Ca 2+ mobilization, which involves Ca 2+ entry. (1,4,5)IP 3 is metabolized by two pathways. One involves the action of a 5-phosphatase that degrades (1,4,5)IP 3 to inositol 1,4-bisphosphate, whereas the other involves a 3-kinase that phosphorylates (1,4,5)IP 3 to produce inositol 1,3,4,5-tetrakisphosphate. The significance of this dual metabolism is not known, but it may be important in rapidly extinguishing the Ca 2+ -releasing activity (1,4,5)IP 3

  6. Turnover in health care: the mediating effects of employee engagement.

    Science.gov (United States)

    Collini, Stevie A; Guidroz, Ashley M; Perez, Lisa M

    2015-03-01

    This study aimed to understand the interaction between interpersonal respect, diversity climate, mission fulfilment and engagement to better predict turnover in health care. Registered nurse turnover has averaged 14% and current nursing shortages are expected to spread. Few studies have studied employee engagement as a mediator between organisational context and turnover. Study participants were employees working within 185 departments across ten hospitals within a large healthcare organisation in the USA. Although a total of 5443 employees work in these departments, employee opinion survey responses were aggregated by department before being linked to turnover rates gathered from company records. Engagement fully mediated the relationship between respect and turnover and the relationship between mission fulfilment and turnover. Diversity climate was not related to turnover. Turnover in health care poses a significant threat to the mission of creating a healing environment for patients and these results demonstrate that workplace respect and connection to the mission affect turnover by decreasing engagement. The findings demonstrated that to increase engagement, and improve turnover rates in health care, it would be beneficial for organisations, and nurse management to focus on improving mission fulfilment and interpersonal relationships. © 2013 John Wiley & Sons Ltd.

  7. Anion-exchange high-performance liquid chromatography with post-column detection for the analysis of phytic acid and other inositol phosphates

    Science.gov (United States)

    Rounds, M. A.; Nielsen, S. S.; Mitchell, C. A. (Principal Investigator)

    1993-01-01

    The use of gradient anion-exchange HPLC, with a simple post-column detection system, is described for the separation of myo-inositol phosphates, including "phytic acid" (myo-inositol hexaphosphate). Hexa-, penta-, tetra-, tri- and diphosphate members of this homologous series are clearly resolved within 30 min. This method should facilitate analysis and quantitation of "phytic acid" and other inositol phosphates in plant, food, and soil samples.

  8. Modulation of agonist-induced inositol phosphate metabolism by cyclic adenosine 3',5'-monophosphate in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Baukal, A.J.; Hunyady, L.; Balla, T.; Ely, J.A.; Catt, K.J.

    1990-01-01

    Activation of the cAMP messenger system was found to cause specific changes in angiotensin-II (All)-induced inositol phosphate production and metabolism in bovine adrenal glomerulosa cells. Pretreatment of [3H]inositol-labeled glomerulosa cells with 8-bromo-cAMP (8Br-cAMP) caused both short and long term changes in the inositol phosphate response to stimulation by All. Exposure to 8Br-cAMP initially caused dose-dependent enhancement (ED50 = 0.7 microM) of the stimulatory action of All (50 nM; 10 min) on the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and its immediate metabolites. This effect of 8Br-cAMP was also observed in permeabilized [3H]inositol-labeled glomerulosa cells in which degradation of Ins(1,4,5)P3 was inhibited, consistent with increased activity of phospholipase-C. Continued exposure to 8Br-cAMP for 5-16 h caused selective enhancement of the All-induced increases in D-myo-inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4] and myo-inositol 1,4,5,6-tetrakisphosphate. The long term effect of 8Br-cAMP on the 6-phosphorylated InsP4 isomers, but not the initial enhancement of Ins(1,4,5)P3 formation, was inhibited by cycloheximide. The characteristic biphasic kinetics of All-induced Ins(1,4,5)P3 formation were also changed by prolonged treatment with 8Br-cAMP to a monophasic response in which Ins(1,4,5)P3 increased rapidly and remained elevated during All stimulation. In permeabilized glomerulosa cells treated with 8Br-cAMP for 16 h, the conversion of D-myo-inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] to Ins(1,3,4,6)P4 was consistently increased, whereas dephosphorylation of Ins(1,4,5)P3 to D-myo-inositol 1,4-bisphosphate and of D-myo-inositol 1,3,4,5-tetrakisphosphate to Ins(1,3,4)P3, was reduced

  9. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes.

    Science.gov (United States)

    Crawford, Tineke J; Crowther, Caroline A; Alsweiler, Jane; Brown, Julie

    2015-12-17

    Gestational diabetes, glucose intolerance with onset or first recognition during pregnancy, is a rising problem worldwide. Both non-pharmacological and pharmacological approaches to the prevention of gestational diabetes have been, and continue to be explored. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. It is one of the intracellular mediators of the insulin signal and correlated with insulin sensitivity in type 2 diabetes. The potential beneficial effect on improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes. We searched the Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, WHO ICTRP (2 November 2015) and reference lists of retrieved studies. We sought published and unpublished randomised controlled trials, including conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes mellitus (GDM). Quasi-randomised and cross-over trials were not eligible for inclusion, but cluster designs were eligible. Participants in the trials were pregnant women. Women with pre-existing type 1 or type 2 diabetes were excluded. Trials that compared the administration of any dose of myo-inositol, alone or in a combination preparation were eligible for inclusion. Trials that used no treatment, placebo or another intervention as the comparator were eligible for inclusion. Two review authors independently assessed trials for inclusion, risk of bias and extracted the data. Data were checked for accuracy. We included four randomised controlled trials (all conducted in Italy) reporting on 567 women who were less than 11 weeks' to 24 weeks' pregnant at the start of the trials. The trials had small sample sizes and one trial only reported an

  10. Myo-inositol-14C, phytic acid-14C and ferric phytate-14C metabolism through microbian action in an andosol soil

    International Nuclear Information System (INIS)

    Gonzalez I, J.

    1977-01-01

    The myo-inositol- 14 C, phytic acid- 14 C and ferric phytate- 14 C compounds were incubated in an andosol soil at 70% of the field capacity and at 36.5 deg C during twelve days. These compounds suffered a microbian oxidation at 14 CO 2 of 61.0, 1.9 and 0% respectively. The fixation of the phytic acid- 14 C was observed through the fast decrease in the metabolism, due to the formation of complexes with the Fe and Al (phytates). The myo-inositol- 14 C metabolism was reduced by a factor of nine at the second incubation day. The following mechanisms were observed in the myo-inositol metabolism: (i) adsorption of the inositol by the soil minerals, (ii) adsorption by humic acids, (iii) myo-inositol phosphorylation and (iv) epimerization of myo-inositol to chiro-inositol. It was found that the (i) and (ii) formation depends on the soil microbian activity. The (i), (ii) and (iii) interactions were considered as possible mechanisms for the inhibition of the myo-inositol microbian oxidation. The inhibition of the myo-inositol oxidation through adsorption or phosphorylation is considered as a chemical blockade for the hydroaxial group, avoiding this way a microbian oxidation stereospecific of this hydroxil group. (author)

  11. DNA turnover in rat cerebral cortex.

    Science.gov (United States)

    Perrone-Capano, C; D'Onofrio, G; Giuditta, A

    1982-01-01

    After the intracranial injection of [methyl-3H]thymidine the specific activity of rat cortical DNA increases rapidly, reaching a maximum at about 5 h. More than half of the radioactive DNA disappears from the tissue in the following few hours. During the same period of time the concentration of radioactive DNA in liver remains essentially constant. Minor variations occur in both organs after 41 h. An apparent rapid turnover of DNA is also present in a fraction of purified neuronal perikarya prepared from the cerebral cortex.

  12. Metabolism of inositol(1,4,5)trisphosphate by a soluble enzyme fraction from pea (Pisum sativum) roots

    International Nuclear Information System (INIS)

    Drobak, B.K.; Watkins, P.A.C.; Roberts, K.; Chattaway, J.A.; Dawson, A.P.

    1991-01-01

    Metabolism of the putative messenger molecule D-myo-inositol(1,4,5)trisphosphate [Ins(1,4,5)P 3 ] in plant cells has been studied using a soluble fraction from pea (pisum sativum) roots as enzyme source and [5- 32 P]Ins(1,4,5)P 3 and [2- 3 H]Ins(1,4,5)P 3 as tracers. Ins(1,4,5)P 3 was rapidly converted into both lower and higher inositol phosphates. The major dephosphorylation product was inositol (4,5) bisphosphate [Ins(4,5)P 2 ] whereas inositol(1,4)bisphosphate [Ins(1,4)P 2 ] was only present in very small quantities throughout a 15 minute incubation period. In addition to these compounds, small amounts of nine other metabolites were produced including inositol and inositol(1,4,5,X)P 4 . Dephosphorylation of Ins(1,4,5)P 3 to Ins(4,5)P 2 was dependent on Ins(1,4,5)P 3 concentration and was partially inhibited by the phosphohydrolase inhibitors 2,3-diphosphoglycerate, glucose 6-phosphate, and p-nitrophenylphosphate. Conversion of Ins(1,4,5)P 3 to Ins(4,5)P 2 and Ins(1,4,5,X)P 4 was inhibited by 55 micromolar Ca 2+ . This study demonstrates that enzymes are present in plant tissues which are capable of rapidly converting Ins(1,4,5)P 3 and that pathways of inositol phosphate metabolism exist which may prove to be unique to the plant kingdom

  13. Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial.

    Science.gov (United States)

    DʼAnna, Rosario; Di Benedetto, Antonino; Scilipoti, Angela; Santamaria, Angelo; Interdonato, Maria Lieta; Petrella, Elisabetta; Neri, Isabella; Pintaudi, Basilio; Corrado, Francesco; Facchinetti, Fabio

    2015-08-01

    To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (α=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. From January 2011 to April 2014, 220 pregnant women at 12-13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17-0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, -1.0±3.1 compared with 0.1±1.8 (P=.048). Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.

  14. PENGARUH KEPUASAN KERJA DAN KOMITMEN ORGANISASI TERHADAP TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    V. Mardi Widyadmono

    2017-04-01

    Full Text Available This study assesses the influence of job satisfaction and organizational commitment on Turnover Intention. Futhermore, the study identify the mediation role of organizational commitment in the relationship between job satifaction and Turnover Intention. The participants of the study are 98 employees working in private companies operated in Yogyakarta, (36 men and 62 women. Respondents complete questionnaire containing questions on job satisfaction variable, questions on organizational commitment and questions on Turnover Intention. The statistics tools applied are regression analysis to assess the relation between variables and Sobel test to measure the mediation role of organizational commitment. The results of the investigation revealed that job satisfication and organizational commitment influence negatively and significantly Turnover Intention. The higher the job satisfication and the organizational commitment of employees lead to the lower Turnover Intention. The organizational commitment does not play mediation role in the relationship between job satisfication and Turnover Intention

  15. Lipid Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They ...

  16. Explaining turnover intention in Korean public community hospitals: occupational differences.

    Science.gov (United States)

    Hwang, Jee-In; Chang, Hyejung

    2008-01-01

    Personnel in public hospitals had relatively low job satisfaction despite of tenure employment. High turnover rates degrade hospital image and incur additional costs related to recruitment and training. The purposes of this study were to describe the occupational differences and to identify factors affecting turnover intention among public hospital personnel. A questionnaire survey was conducted as part of Administrative Services Quality Evaluation Program by Seoul metropolitan municipality from 1 November to 1 December in 2003. The subjects were 1251 entire hospital personnel in four hospitals. The questionnaire was designed to measure job satisfaction, organizational commitment, turnover intention, and demographic characteristics. Logistic regression analysis was performed to determine factors influencing turnover intention. There were significant differences in job satisfaction, organizational commitment, and turnover intention according to the occupations. The turnover intention rates were highest among physicians, followed by paramedicals and nursing staffs and then administrators. The significant factors affecting turnover intention were involvement and loyalty among physicians, hospital type, satisfaction with systems and loyalty among nursing staffs, satisfaction with relationship and loyalty among administrators, and loyalty among paramedicals. There were different moderators that influence turnover intentions of hospital personnel. Loyalty had the most important effect upon turnover intention in all occupations. 2007 John Wiley & Sons, Ltd

  17. Relationships between Bone Turnover and Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Tânia A. P. Fernandes

    2017-01-01

    Full Text Available It is well established that diabetes can be detrimental to bone health, and its chronic complications have been associated with an increased risk of osteoporotic fracture. However, there is growing evidence that the skeleton plays a key role in a whole-organism approach to physiology. The hypothesis that bone may be involved in the regulation of physiological functions, such as insulin sensitivity and energy metabolism, has been suggested. Given the roles of insulin, adipokines, and osteocalcin in these pathways, the need for a more integrative conceptual approach to physiology is emphasized. Recent findings suggest that bone plays an important role in regulating intermediary metabolism, being possibly both a target of diabetic complications and a potential pathophysiologic factor in the disease itself. Understanding the relationships between bone turnover and glucose metabolism is important in order to develop treatments that might reestablish energy metabolism and bone health. This review describes new insights relating bone turnover and energy metabolism that have been reported in the literature.

  18. Synergism between inositol polyphosphates and TOR kinase signaling in nutrient sensing, growth control, and lipid metabolism in Chlamydomonas

    Science.gov (United States)

    The networks that govern carbon metabolism and control intracellular carbon partitioning in photosynthetic cells are poorly understood. Target of rapamycin (TOR) kinase is a conserved growth regulator that integrates nutrient signals and modulates cell growth in eukaryotes, though the TOR signaling ...

  19. [3H]Indole-3-acetyl-myo-inositol hydrolysis by extracts of Zea mays L. vegetative tissue

    Science.gov (United States)

    Hall, P. J.; Bandurski, R. S.

    1986-01-01

    [3H]Indole-3-acetyl-myo-inositol was hydrolyzed by buffered extracts of acetone powders prepared from 4 day shoots of dark grown Zea mays L. seedlings. The hydrolytic activity was proportional to the amount of extract added and was linear for up to 6 hours at 37 degrees C. Boiled or alcohol denatured extracts were inactive. Analysis of reaction mixtures by high performance liquid chromatography demonstrated that not all isomers of indole-3-acetyl-myo-inositol were hydrolyzed at the same rate. Buffered extracts of acetone powders were prepared from coleoptiles and mesocotyls. The rates of hydrolysis observed with coleoptile extracts were greater than those observed with mesocotyl extracts. Active extracts also catalyzed the hydrolysis of esterase substrates such as alpha-naphthyl acetate and the methyl esters of indoleacetic acid and naphthyleneacetic acid. Attempts to purify the indole-3-acetyl-myo-inositol hydrolyzing activity by chromatographic procedures resulted in only slight purification with large losses of activity. Chromatography over hydroxylapatite allowed separation of two enzymically active fractions, one of which catalyzed the hydrolysis of both indole-3-acetyl-myo-inositol and esterase substrates. With the other enzymic hydrolysis of esterase substrates was readily demonstrated, but no hydrolysis of indole-3-acetyl-myo-inositol was ever detected.

  20. Methyl-inositol, γ-aminobutyric acid and other health benefit compounds in the aril of litchi.

    Science.gov (United States)

    Wu, Zi-Chen; Yang, Zhuan-Ying; Li, Jian-Guo; Chen, Hou-Bin; Huang, Xu-Ming; Wang, Hui-Cong

    2016-11-01

    The available components in the flesh of litchi seem insufficient to interpret its wide and significant physiological effects. Some unusual compounds, including myo-inositol, inositol methyl derivatives and γ-aminobutyric acid (GABA) were identified as main constituents in the flesh of litchi. Their concentrations varied among cultivars but remain relatively constant during development. Litchi flesh was shown to contain moderate myo-inositol (0.28-0.78 mg g(-1) FW), ascorbic acid (0.08-0.39 mg g(-1) FW) and phenolics (0.47-1.60 mg g(-1) FW), but abundant l-quebrachitol (1.6-6.4 mg g(-1) FW) and GABA (1.7-3.5 mg g(-1) FW). The concentration of GABA in the flesh of litchi was about 100 times higher than in other fruits. And l-quebrachitol is not a common component in fruits. The biological and physiological activities of inositols, inositol derivatives and GABA have been extensively documented. These compounds are probably important compositional characteristic contributing to the widely shown health benefits of litchi.

  1. Identification, purification, characterization and regulation of the rabbit peritoneal neutrophil cytosolic inositol 1,4,5-trisphosphate 5-phosphomonoesterase

    International Nuclear Information System (INIS)

    Kennedy, S.P.

    1988-01-01

    Inositol 1,4,5-trisphosphate (IP 3 ) is a second messenger involved in intracellular Ca 2+ mobilization. Its enzymatic breakdown by inositol 1,4,5-trisphosphate 5-phosphomonoesterase (IP 3 phosphatase) yields inositol 1,4-bisphosphate (IP 2 ) which does not mobilize Ca 2+ . Thus, the IP 3 phosphatase can serve to regulate internal free Ca 2+ levels. In Triton X-100 permeabilized rabbit peritoneal neutrophils and neutrophil cytosol, exogenously added [ 3 H]IP 3 is rapidly hydrolyzed to IP 2 , inositol monophosphate (IP) and free inositol. The rate of IP 3 hydrolysis was greater than that of IP 2 in permeabilized neutrophils, while the converse was observed in cytosol. DE-52 chromatography of cytosol separates the specific from nonspecific IP 3 phosphatase activity. Further purification of the specific enzyme resulted in a 790-fold purification over cytosol activity, however, the IP 3 phosphatase could not be identified with any protein in this preparation. The neutrophil IP 3 phosphatase has a molecular weight of 43-47 kDa, and an isoelectric point of 5.6, as determined by size exclusion chromatography and Chromatofocusing, respectively. Physiological concentrations of Ca 2+ and calmodulin have no effect on IP 3 phosphatase activity. Activation of endogenous protein kinase C in permeabilized cells and cytosol also has no effect on the activity. Characteristics of the neutrophil IP 3 phosphatase are discussed in relation to IP 3 phosphatases in other cells and tissues

  2. Inhibitory effect of diazepam on muscarinic receptor-stimulated inositol 1,4,5-trisphosphate production in rat parotid acinar cells

    Science.gov (United States)

    Kujirai, Masao; Sawaki, Kohei; Kawaguchi, Mitsuru

    2002-01-01

    This study examined the effect of diazepam (DZP) on phosphoinositide turnover, which plays an important role in the regulation of salivary secretion, in rat parotid acinar cells. DZP (10−9 M to 10−5 M), a potent agonist of both central- and peripheral-type benzodiazepine receptors, dose-dependently decreased inositol 1,4,5-trisphosphate (IP3) production stimulated by carbachol, a muscarinic receptor agonist, in the cells. DZP produced a maximum inhibitory response at a concentration of 10−5 M, with IP3 production decreased to 63% of maximal levels. The concentration inducing half maximal inhibition of IP3 production was approximately 3.5×10−8 M. An inhibitory response to DZP was produced by a short-term pretreatment (benzodiazepine receptors, flumazenil and PK 11195, respectively. DZP showed a non-competitive inhibition of carbachol-stimulated IP3 production. It did not directly inhibit the activities of GTP-binding regulatory proteins and phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PLC) in the parotid gland membranes, though choline chloride inhibited PLC activity. DZP (10−5 M) attenuated the increase in the intracellular Ca2+ concentration ([Ca2+]i) in the cells following stimulation of the muscarinic and α1-adrenoceptors. These results suggest that in the parotid acinar cells, DZP inhibits muscarinic receptor-stimulated IP3 production through benzodiazepine receptors and that PLC activity which produces IP3 is inhibited by chloride. The decreases in IP3 and [Ca2+]i in the cells may be connected with the suppression of salivary secretion induced by DZP. PMID:12429566

  3. N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus.

    Science.gov (United States)

    Petroff, Ognen A C; Errante, Laura D; Kim, Jung H; Spencer, Dennis D

    2003-05-27

    Mesial temporal lobe epilepsy (mTLE) is characterized by hippocampal atrophy, decreased N-acetyl-aspartate, and a low N-acetyl-aspartate/total creatine ratio, often attributed to neuron loss and gliosis. Qualitative studies reported that N-acetyl-aspartate content was significantly lower in hippocampal sclerosis. It was proposed to measure the effects of neuron loss and gliosis on the hippocampal content of N-acetyl-aspartate, total creatine, and myo-inositol in mTLE. Twenty hippocampal specimens were obtained during temporal lobectomy and frozen quickly. Perchloric acid extracts of the small metabolites were prepared and analyzed by proton MRS at 11.75 T. Adjacent samples were used for cell counts. There were no significant associations between hippocampal neuron loss and the cellular content of N-acetyl-aspartate, total creatine, or myo-inositol, despite more than a threefold difference in neuron loss and a twofold increase in glial density. Metabolite concentrations varied two- to fourfold. Variation in the cellular content of total creatine accounted for more than three-quarters of the rank-order variance of the N-acetyl-aspartate concentrations. There were no associations between myo-inositol and N-acetyl-aspartate or total creatine. Overall, mean N-acetyl-aspartate levels were below those reported by in vivo MRS studies of control subjects. These data suggest that decreased N-acetyl-aspartate in mesial temporal lobe epilepsy reflects altered mitochondrial metabolism, not merely neuron loss or gliosis. It is hypothesized that the altered N-acetyl-aspartate and creatine metabolism could reflect mitochondrial dysfunction or proliferation of immature glial cells that could contribute to the epileptogenic state.

  4. Inositol-trisphosphate reduces alveolar apoptosis and pulmonary edema in neonatal lung injury.

    Science.gov (United States)

    Preuss, Stefanie; Stadelmann, Sabrina; Omam, Friede D; Scheiermann, Julia; Winoto-Morbach, Supandi; von Bismarck, Philipp; Knerlich-Lukoschus, Friederike; Lex, Dennis; Adam-Klages, Sabine; Wesch, Daniela; Held-Feindt, Janka; Uhlig, Stefan; Schütze, Stefan; Krause, Martin F

    2012-08-01

    D-myo-inositol-1,2,6-trisphosphate (IP3) is an isomer of the naturally occurring second messenger D-myo-inositol-1,4,5-trisphosphate, and exerts anti-inflammatory and antiedematous effects in the lung. Myo-inositol (Inos) is a component of IP3, and is thought to play an important role in the prevention of neonatal pulmonary diseases such as bronchopulmonary dysplasia and neonatal acute lung injury (nALI). Inflammatory lung diseases are characterized by augmented acid sphingomyelinase (aSMase) activity leading to ceramide production, a pathway that promotes increased vascular permeability, apoptosis, and surfactant alterations. A novel, clinically relevant triple-hit model of nALI was developed, consisting of repeated airway lavage, injurious ventilation, and lipopolysaccharide instillation into the airways, every 24 hours. Thirty-five piglets were randomized to one of four treatment protocols: control (no intervention), surfactant alone, surfactant + Inos, and surfactant + IP3. After 72 hours of mechanical ventilation, lungs were excised from the thorax for subsequent analyses. Clinically, oxygenation and ventilation improved, and extravascular lung water decreased significantly with the S + IP3 intervention. In pulmonary tissue, we observed decreased aSMase activity and ceramide concentrations, decreased caspase-8 concentrations, reduced alveolar epithelial apoptosis, the reduced expression of interleukin-6, transforming growth factor-β1, and amphiregulin (an epithelial growth factor), reduced migration of blood-borne cells and particularly of CD14(+)/18(+) cells (macrophages) into the airspaces, and lower surfactant surface tensions in S + IP3-treated but not in S + Inos-treated piglets. We conclude that the admixture of IP3 to surfactant, but not of Inos, improves gas exchange and edema in our nALI model by the suppression of the governing enzyme aSMase, and that this treatment deserves clinical evaluation.

  5. General amyloid inhibitors? A critical examination of the inhibition of IAPP amyloid formation by inositol stereoisomers.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available Islet amyloid polypeptide (IAPP or amylin forms amyloid deposits in the islets of Langerhans; a process that is believed to contribute to the progression of type 2 diabetes and to the failure of islet transplants. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation by different polypeptides share common features and exert their effects by common mechanisms. If correct, this suggests that inhibitors of amyloid formation by one polypeptide might be effective against other amyloidogenic sequences. IAPP and Aβ, the peptide responsible for amyloid formation in Alzheimer's disease, are particularly interesting in this regard as they are both natively unfolded in their monomeric states and share some common characteristics. Comparatively little effort has been expended on the design of IAPP amyloid inhibitors, thus it is natural to inquire if Aβ inhibitors are effective against IAPP, especially since no IAPP inhibitors have been clinically approved. A range of compounds inhibit Aβ amyloid formation, including various stereoisomers of inositol. Myo-, scyllo-, and epi-inositol have been shown to induce conformational changes in Aβ and prevent Aβ amyloid fibril formation by stabilizing non-fibrillar β-sheet structures. We investigate the ability of inositol stereoisomers to inhibit amyloid formation by IAPP. The compounds do not induce a conformational change in IAPP and are ineffective inhibitors of IAPP amyloid formation, although some do lead to modest apparent changes in IAPP amyloid fibril morphology. Thus not all classes of Aβ inhibitors are effective against IAPP. This work provides a basis of comparison to work on polyphenol based inhibitors of IAPP amyloid formation and helps provide clues as to the features which render them effective. The study also helps provide information for further efforts in rational inhibitor design.

  6. Cellular internalisation of an inositol phosphate visualised by using fluorescent InsP5.

    Science.gov (United States)

    Riley, Andrew M; Windhorst, Sabine; Lin, Hong-Yin; Potter, Barry V L

    2014-01-03

    When applied extracellularly, myo-inositol hexakisphosphate (InsP6 ) and myo-inositol pentakisphosphate (InsP5 ) can inhibit the growth and proliferation of tumour cells. There is debate about whether these effects result from interactions of InsP6 and InsP5 with intracellular or extracellular targets. We synthesised FAM-InsP5 , a fluorescent conjugate of InsP5 that allows direct visualisation of its interaction with cells. FAM-InsP5 was internalised by H1229 tumour cells, a finding that supports earlier reports that externally applied inositol phosphates can-perhaps surprisingly-enter into cells. Close examination of the process of FAM-InsP5 uptake suggests a mechanism of non-receptor-mediated endocytosis, which is blocked at 4 °C and probably involves interaction of the ligand with the glycocalyx. However, our results are difficult to reconcile with antiproliferative mechanisms that require direct interactions of externally applied InsP5 or InsP6 with cytosolic proteins, because internalised FAM-InsP5 appears in lysosomes and apparently does not enter the cytoplasm. Studies using FAM-InsP5 are less difficult and time-consuming than experiments using InsP5 or InsP6 , a factor that allowed us to analyse cellular uptake across a range of human cell types, identifying strong cell-specific differences. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Prefrontal inositol levels and implicit decision-making in healthy individuals and depressed patients.

    Science.gov (United States)

    Jollant, Fabrice; Richard-Devantoy, Stéphane; Ding, Yang; Turecki, Gustavo; Bechara, Antoine; Near, Jamie

    2016-08-01

    Risky decision-making is found in several mental disorders and is associated with deleterious consequences. Current research aims at understanding the biological underpinnings of this complex cognitive function and the basis of individual variability. We used 3T proton Magnetic Resonance Spectroscopy to measure in vivo glutamate, GABA, N-acetyl-aspartate (NAA), and myo-inositol levels at rest in the right dorsal prefrontal cortex of 54 participants, comprising 24 unmedicated depressed patients and 30 healthy individuals. Participants were also tested with the Iowa Gambling Task (IGT), a classical measure of value-based decision-making. No group differences were found in terms of compound levels or decision-making performance. However, high inositol levels were associated with lower decision-making scores independently from group, notably during the initial stage of the task when explicit rules are still unknown and decisions are largely based on implicit processes (whole sample: F=4.0; p=0.02), with a large effect size (Cohen׳s d=0.8, 95% [0.2-1.5]). This effect was stronger when explicit knowledge was taken into account, with explicit knowledge showing an independent effect on performance. There was no association with other compounds. This study suggests, for the first time, a role for the inositol pathway on the implicit learning component of decision-making, without any direct effect on the explicit component. Hypothesized mechanisms implicate intracellular calcium modulation and subsequent synaptic plasticity. These findings represent a first step in the understanding of the biochemical mechanisms underlying decision-making and the identification of therapeutic targets. They also emphasize a dimensional approach in the study of the neurobiological determinants of mental disorders. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  8. General Amyloid Inhibitors? A Critical Examination of the Inhibition of IAPP Amyloid Formation by Inositol Stereoisomers

    Science.gov (United States)

    Wang, Hui; Raleigh, Daniel P.

    2014-01-01

    Islet amyloid polypeptide (IAPP or amylin) forms amyloid deposits in the islets of Langerhans; a process that is believed to contribute to the progression of type 2 diabetes and to the failure of islet transplants. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation by different polypeptides share common features and exert their effects by common mechanisms. If correct, this suggests that inhibitors of amyloid formation by one polypeptide might be effective against other amyloidogenic sequences. IAPP and Aβ, the peptide responsible for amyloid formation in Alzheimer's disease, are particularly interesting in this regard as they are both natively unfolded in their monomeric states and share some common characteristics. Comparatively little effort has been expended on the design of IAPP amyloid inhibitors, thus it is natural to inquire if Aβ inhibitors are effective against IAPP, especially since no IAPP inhibitors have been clinically approved. A range of compounds inhibit Aβ amyloid formation, including various stereoisomers of inositol. Myo-, scyllo-, and epi-inositol have been shown to induce conformational changes in Aβ and prevent Aβ amyloid fibril formation by stabilizing non-fibrillar β-sheet structures. We investigate the ability of inositol stereoisomers to inhibit amyloid formation by IAPP. The compounds do not induce a conformational change in IAPP and are ineffective inhibitors of IAPP amyloid formation, although some do lead to modest apparent changes in IAPP amyloid fibril morphology. Thus not all classes of Aβ inhibitors are effective against IAPP. This work provides a basis of comparison to work on polyphenol based inhibitors of IAPP amyloid formation and helps provide clues as to the features which render them effective. The study also helps provide information for further efforts in rational inhibitor design. PMID:25260075

  9. THE ROLE OF INOSITOL 1,3,4,5-TETRAKISPHOSPHATE IN INTERNAL CA2+ MOBILIZATION FOLLOWING HISTAMINE H-1 RECEPTOR STIMULATION IN DDT1 MF-2 CELLS

    NARCIS (Netherlands)

    VANDERZEE, L; SIPMA, H; NELEMANS, A; DENHERTOG, A

    1995-01-01

    Receptor-activated formation of inositol phosphates results in mobilization of intracellular stored Ca2+ in a variety of cells, including vas deferens derived DDT1 MF-2 cells. Stimulation of the histamine H-1 receptor on these cells caused a pronounced formation of inositol 1,3,4,5-tetrakisphosphate

  10. A cold-induced myo-inositol transporter-like gene confers tolerance to multiple abiotic stresses in transgenic tobacco plants.

    Science.gov (United States)

    Sambe, Mame Abdou Nahr; He, Xueying; Tu, Qinghua; Guo, Zhenfei

    2015-03-01

    A full length cDNA encoding a myo-inositol transporter-like protein, named as MfINT-like, was cloned from Medicago sativa subsp. falcata (herein falcata), a species with greater cold tolerance than alfalfa (M. sativa subsp. sativa). MfINT-like is located on plasma membranes. MfINT-like transcript was induced 2-4 h after exogenous myo-inositol treatment, 24-96 h with cold, and 96 h by salinity. Given that myo-inositol accumulates higher in falcata after 24 h of cold treatment, myo-inositol is proposed to be involved in cold-induced expression of MfINT-like. Higher levels of myo-inositol was observed in leaves of transgenic tobacco plants overexpressing MfINT-like than the wild-type but not in the roots of plants grown on myo-inositol containing medium, suggesting that transgenic plants had higher myo-inositol transport activity than the wild-type. Transgenic plants survived better to freezing temperature, and had lower ion leakage and higher maximal photochemical efficiency of photosystem II (Fv /Fm ) after chilling treatment. In addition, greater plant fresh weight was observed in transgenic plants as compared with the wild-type when plants were grown under drought or salinity stress. The results suggest that MfINT-like mediated transport of myo-inositol is associated with plant tolerance to abiotic stresses. © 2014 Scandinavian Plant Physiology Society.

  11. P2 PURINOCEPTOR-MEDIATED INOSITOL PHOSPHATE FORMATION IN RELATION TO CYTOPLASMIC CALCIUM IN DDT1 MF-2 SMOOTH-MUSCLE CELLS

    NARCIS (Netherlands)

    HOITING, B; MOLLEMAN, A; DUIN, M; DENHERTOG, A; NELEMANS, A

    1990-01-01

    The effect of P2 purinoceptor stimulation on inositol phosphate (InsP) formation in relation to the intracellular Ca2+ concentration was measured in vas deferens DDT1 MF-2 smooth muscle cells. The different [H-3]myo-inositol-labelled InsP fractions were analyzed by high performance liquid

  12. ALPHA-ADRENOCEPTOR REGULATION OF INOSITOL PHOSPHATES, INTERNAL CALCIUM AND MEMBRANE CURRENT IN DDT1 MF-2 SMOOTH-MUSCLE CELLS

    NARCIS (Netherlands)

    NELEMANS, A; HOITING, B; MOLLEMAN, A; DUIN, M; DENHERTOG, A

    1990-01-01

    The effect of alpha-1-adrenoceptor stimulation on inositol phosphates (InsPs), intracellular Ca2+ and membrane current was measured in vas deferens DDT1 MF-2 cells. The InsPs were analyzed after labelling the cells with [H-3]myo-inositol using high performance liquid chromatography and the internal

  13. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C

    1993-01-01

    Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found...... in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  14. Organizational commitment and turnover intentions in humanitarian organizations

    NARCIS (Netherlands)

    Wijnmalen, Julia; Heyse, Liesbet; Voordijk, Hans

    2016-01-01

    Unwanted staff turnover is a prominent HRM problem in humanitarian organisations. In the profit sector, HRM tools such as pay, benefits, socialisation and training have proven to be effective in increasing organisational commitment and decreasing staff turnover. This study explores whether such

  15. Health workforce acquisition, retention and turnover in southwest ...

    African Journals Online (AJOL)

    Background: Skill mix of health professionals, staff acquisition and turnover rate are among the major challenges for the delivery of quality health care. This study assessed the health workforce acquisition, retention, turnover rate and their intention to leave. Methods: A cross-sectional survey with quantitative and qualitative ...

  16. Work-life balance, job satisfaction and turnover intention amongst

    African Journals Online (AJOL)

    kirstam

    consider the relationships between work-life balance, job satisfaction and turnover intention. 21Key words: Knowledge workers, IT employees, work-life balance, job satisfaction, turnover intention, talent management, talent retention. Prof. R.M. Oosthuizen and Prof. M. Coetzee are in the Department of Industrial and ...

  17. Below the Surface of Special Education Administrator Turnover

    Science.gov (United States)

    Meeks, Amy

    2016-01-01

    The field of special education administration has experienced a shortage of high quality special education leadership candidates for several decades. If school districts are to effectively address the turnover of educational leaders, they must know what is happening that affects turnover of their leadership team. The intent of this study was to…

  18. Survey of pay satisfaction, job satisfaction and employee turnover in ...

    African Journals Online (AJOL)

    Survey of pay satisfaction, job satisfaction and employee turnover in selected business organisations in Lagos, Nigeria. ... Global Journal of Social Sciences ... The study was an attempt at investigating the relatedness of pay satisfaction, job satisfaction and employee turnover in business organizations in Lagos Nigeria.

  19. Voluntary Turnover and Women Administrators in Higher Education

    Science.gov (United States)

    Jo, Victoria H.

    2008-01-01

    A salient characteristic about the U.S. workforce is the continual process of voluntary employee turnover, which can be problematic for employers who invest a substantial amount of time and money in recruiting and training employees. This paper discusses the effects of workplace policies and practices on the voluntary turnover of women…

  20. Second trimester amniotic fluid myo-inositol concentrations in women later developing gestational diabetes mellitus or pregnancy-induced hypertension.

    Science.gov (United States)

    Santamaria, Angelo; Corrado, Francesco; Baviera, Giovanni; Carlomagno, Gianfranco; Unfer, Vittorio; D'anna, Rosario

    2016-01-01

    To evaluate myo-inositol concentrations in amniotic fluid in women later developing gestational diabetes and hypertension. A retrospective study was carried out with three groups of amniotic fluid samples (15-18 gestational weeks): 30 gestational hypertension pregnancies, 30 gestational diabetes pregnancies, and 30 normal pregnancy. A significant difference was observed in myo-inositol concentrations between the median gestational diabetes values (124.0 µmol/L, IQR 90.0-162.5) and the control group values (79.0 µmol/L, IQR 62.0-107.5), but also with gestational hypertension median values (79.0 µmol/L, IQR 67.75-92.0) (p inositol concentrations in amniotic fluid increased significantly in women later developing gestational diabetes compared to the control group.

  1. Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts.

    OpenAIRE

    Bunce, C M; French, P J; Allen, P; Mountford, J C; Moor, B; Greaves, M F; Michell, R H; Brown, G

    1993-01-01

    We have compared the levels of inositol metabolites in three pairs of normal and transformed cells which have been matched with respect to their cell lineage, differentiation and proliferation status: (i) normal human myeloid blast cells and the human promyelocytic leukaemic cell line, HL60; (ii) human umbilical-cord T-helper cells and C8166 cells, a HTLV-1-transformed T-helper cell line; and (iii) an interleukin 3-dependent long-term culture of murine pro-B-cells (BAF3) and BAF3 cells transf...

  2. Adenosine (ADO) released during orthodromic stimulation of the frog sympathetic ganglion inhibits phosphatidylinositol turnover (PI) associated with synaptic transmission

    International Nuclear Information System (INIS)

    Curnish, R.; Bencherif, M.; Rubio, R.; Berne, R.M.

    1986-01-01

    The authors have previously demonstrated that 3 H-purine release was enhanced during synaptic activation of the prelabelled frog sympathetic ganglion. In addition, during orthodromic stimulation, there is an increased 3 H-inositol release (an index of PI) that occurs during the poststimulation period and not during the period of stimulation. They hypothesized that endogenous ADO inhibits PI turnover during orthodromic stimulation. To test this hypothesis (1) they performed experiments to directly measure ADO release in the extracellular fluid by placing the ganglion in a 5 μl drop of Ringer's and let it come to equilibrium with the interstitial fluid, (2) they destroyed endogenous ADO by suffusing adenosine deaminase (ADA) during the stimulation period. Their results show (1) orthodromic stimulation increases release of ADO into the bathing medium, (2) ADA induced an increase of PI during the stimulation period in contrast to an increase seen only during the poststimulation period when ADA was omitted. They conclude that there is dual control of PI during synaptic activity, a stimulatory effect (cause unknown) and a short lived inhibitory effect that is probably caused by adenosine

  3. PENGARUH KEPUASAN KERJA TERHADAP KOMITMEN ORGANISASI DAN TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Agi Syarif Hidayat

    2018-03-01

    Full Text Available The high level of employee turnover in the marketing department at PT. Toyamilindo indicates low organizational commitment and high turnover intention. The purpose of this study is to determine the effect of job satisfaction on organizational commitment and turnover intention. Quantitative methods are used in this study. Population is the  employees of marketing department at PT. Toyamilindo with 50 people. Sampling technique used is sampling saturated with the number of samples of 50 people. Data collection technique uses questionnaires and regression analysis. Finding on the research results shows that there are positive and significant influence of job satisfaction on organizational commitment and negative and significant influence of job satisfaction on turnover intention, and also the influence of organizational commitment on work satisfaction to turnover intention. The managerial implications of corporate leaders must improve employee work satisfaction, especially in terms of salary.

  4. One hundred years of employee turnover theory and research.

    Science.gov (United States)

    Hom, Peter W; Lee, Thomas W; Shaw, Jason D; Hausknecht, John P

    2017-03-01

    We review seminal publications on employee turnover during the 100-year existence of the Journal of Applied Psychology . Along with classic articles from this journal, we expand our review to include other publications that yielded key theoretical and methodological contributions to the turnover literature. We first describe how the earliest papers examined practical methods for turnover reduction or control and then explain how theory development and testing began in the mid-20th century and dominated the academic literature until the turn of the century. We then track 21st century interest in the psychology of staying (rather than leaving) and attitudinal trajectories in predicting turnover. Finally, we discuss the rising scholarship on collective turnover given the centrality of human capital flight to practitioners and to the field of human resource management strategy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Pitfalls in quantifying species turnover: the residency effect

    Directory of Open Access Journals (Sweden)

    Kevin Chase Burns

    2014-03-01

    Full Text Available The composition of ecological communities changes continuously through time and space. Understanding this turnover in species composition is a central goal in biogeography, but quantifying species turnover can be problematic. Here, I describe an underappreciated source of bias in quantifying species turnover, namely ‘the residency effect’, which occurs when the contiguous distributions of species across sampling domains are small relative to census intervals. I present the results of a simulation model that illustrates the problem theoretically and then I demonstrate the problem empirically using a long-term dataset of plant species turnover on islands. Results from both exercises indicate that empirical estimates of species turnover may be susceptible to significant observer bias, which may potentially cloud a better understanding of how the composition of ecological communities changes through time.

  6. Rv2131c gene product: An unconventional enzyme that is both inositol monophosphatase and fructose-1,6-bisphosphatase

    International Nuclear Information System (INIS)

    Gu Xiaoling; Chen Mao; Shen Hongbo; Jiang Xin; Huang Yishu; Wang Honghai

    2006-01-01

    Inositol monophosphatase is an enzyme in the biosynthesis of myo-inostiol, a crucial substrate for the synthesis of phosphatidylinositol, which has been demonstrated to be an essential component of mycobacteria. In this study, the Rv2131c gene from Mycobacterium tuberculosis H37Rv was cloned into the pET28a vector and the recombinant plasmid was transformed into Escherichia coli BL21 (DE3) strain, allowing the expression of the enzyme in fusion with a histidine-rich peptide on the N-terminal. The fusion protein was purified from the soluble fraction of the lysed cells under native conditions by immobilized metal affinity chromatography (IMAC). The purified Rv2131c gene product showed inositol monophosphatase activity but with substrate specificity that was broader than those of several bacterial and eukaryotic inositol monophosphatases, and it also acted as fructose-1,6-bisphosphatase. The dimeric enzyme exhibited dual activities of IMPase and FBPase, with K m of 0.22 ± 0.03 mM for inositol-1-phosphate and K m of 0.45 ± 0.05 mM for fructose-1,6-bisphosphatase. To better understand the relationship between the function and structure of the Rv2131c enzyme, we constructed D40N, L71A, and D94N mutants and purified these corresponding proteins. Mutations of D40N and D94N caused the proteins to almost completely lose both the inositol monophosphatase and fructose-1,6-bisphosphatase activities. However, L71A mutant did not cause loss either of the activities, but the activity toward the inositol was 12-fold more resistant to inhibition by lithium (IC 5 ∼ 60 mM). Based on the substrate specificity and presence of conserved sequence motifs of the M. tuberculosis Rv2131c, we proposed that the enzyme belonged to class IV fructose-1,6-bisphosphatase (FBPase IV)

  7. Effects of the hexahydroxyhexane myoinositol on bone uptake of radiocalcium in rats: Effect of inositol and vitamin D2 on bone uptake of 45Ca in rats

    International Nuclear Information System (INIS)

    Angeloff, L.G.; Skoryna, S.C.; Henderson, I.W.D.

    1977-01-01

    The objective of this study was to investigate the effects of inositol and vitamin D 2 on bone uptake of 45 Ca in rats. The radioactive calcium was administered to young rats by orogastric intubation (2 μci/100 g body weight (b.wt.)) with inositol (20 mg/100 g b.wt) and/or vitamin D 2 (500 IU/100g b.wt) to normal rats. Bone uptake of 45 Ca was measured after 24 hours by standard technique. Inositol alone produced a 48% increase in calcium uptake. It is concluded that inositol significantly increases bone uptake to radioactive calcium (P>0.005). Simultaneous administration of vitamin D 2 decreases the effect of inositol considerably, while vitamin D 2 has no significant effect. (author)

  8. Effect of exogenous phytase on feed inositol phosphate hydrolysis in an in vitro rumen fluid buffer system

    DEFF Research Database (Denmark)

    Brask-Pedersen, Dorte Niss; Glitsø, Lene Vibe; Skov, L.K.

    2011-01-01

    for inositol phosphates via high performance ion chromatography. Addition of phytase (Phy1) resulted in enhanced degradation of myo-inositol hexakisphosphate (InsP6) in rapeseed cake, whereas addition of exogenous phytase did not improve the degradation of InsP6 in wheat. Only rapeseed cake was therefore used...... when 5 mg of enzyme protein per gram of substrate of Phy2 was added to rapeseed cake, whereas 150 mg of enzyme protein per gram of substrate of Phy4 was necessary to achieve a similar result. Therefore, Phy2 appeared to be most applicable under rumen-like conditions...

  9. Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

    Directory of Open Access Journals (Sweden)

    Charlotte Collet

    2016-02-01

    Full Text Available Efficient routes were developed for the diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues. The key steps of the synthesis were the easy accessibility of different types of arms in term of configuration (myo and scyllo, the linking method and length, which could modulate the biological properties. These inositol derivatives, bearing an arm terminated either with a hydroxy group or a fluorine atom, could be interesting candidates for diastereoisomeric intermediates and biological evaluations, especially for PET imaging experiments.

  10. Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology

    Science.gov (United States)

    Fenili, Daniela; Weng, Ying-Qi; Aubert, Isabelle; Nitz, Mark; McLaurin, JoAnne

    2011-01-01

    Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain and are significantly elevated following oral administration. Elevations in brain inositol levels occur across a concentration gradient as a result of active transport from the periphery. There are two sodium/myo-inositol transporters (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The goals of this study were to determine the effects of aging and Alzheimer's disease (AD)-like amyloid pathology on transporter expression, to compare regional expression and to analyze substrate requirements of the inositol transporters. QPCR was used to examine expression of the two transporters in the cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid pathology, in comparison to non-transgenic littermates. In addition, we examined the structural features of inositol required for active transport, utilizing a cell-based competitive uptake assay. Disease pathology did not alter transporter expression in the cortex or hippocampus (p>0.005), with only minimal effects of aging observed in the cerebellum (SMIT1: F2,26 = 12.62; p = 0.0002; SMIT2: F2,26 = 8.71; p = 0.0015). Overall, brain SMIT1 levels were higher than SMIT2, however, regional differences were observed. For SMIT1, at 4 and 6 months cerebellar SMIT1 levels were significantly higher than cortical and hippocampal levels (pInositol transporter levels are stably expressed as a function of age, and expression is unaltered with disease pathology in the TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical trials for the treatment of AD, the stable expression of inositol transporters regardless of disease pathology is an important finding. PMID:21887366

  11. Differential effects of Mycobacterium bovis - derived polar and apolar lipid fractions on bovine innate immune cells

    Directory of Open Access Journals (Sweden)

    Pirson Chris

    2012-06-01

    Full Text Available Abstract Mycobacterial lipids have long been known to modulate the function of a variety of cells of the innate immune system. Here, we report the extraction and characterisation of polar and apolar free lipids from Mycobacterium bovis AF 2122/97 and identify the major lipids present in these fractions. Lipids found included trehalose dimycolate (TDM and trehalose monomycolate (TMM, the apolar phthiocerol dimycocersates (PDIMs, triacyl glycerol (TAG, pentacyl trehalose (PAT, phenolic glycolipid (PGL, and mono-mycolyl glycerol (MMG. Polar lipids identified included glucose monomycolate (GMM, diphosphatidyl glycerol (DPG, phenylethanolamine (PE and a range of mono- and di-acylated phosphatidyl inositol mannosides (PIMs. These lipid fractions are capable of altering the cytokine profile produced by fresh and cultured bovine monocytes as well as monocyte derived dendritic cells. Significant increases in the production of IL-10, IL-12, MIP-1β, TNFα and IL-6 were seen after exposure of antigen presenting cells to the polar lipid fraction. Phenotypic characterisation of the cells was performed by flow cytometry and significant decreases in the expression of MHCII, CD86 and CD1b were found after exposure to the polar lipid fraction. Polar lipids also significantly increased the levels of CD40 expressed by monocytes and cultured monocytes but no effect was seen on the constitutively high expression of CD40 on MDDC or on the levels of CD80 expressed by any of the cells. Finally, the capacity of polar fraction treated cells to stimulate alloreactive lymphocytes was assessed. Significant reduction in proliferative activity was seen after stimulation of PBMC by polar fraction treated cultured monocytes whilst no effect was seen after lipid treatment of MDDC. These data demonstrate that pathogenic mycobacterial polar lipids may significantly hamper the ability of the host APCs to induce an appropriate immune response to an invading pathogen.

  12. Inositol Hexakisphosphate Mediates Apoptosis in Human Breast Adenocarcinoma MCF-7 Cell Line via Intrinsic Pathway

    Science.gov (United States)

    Agarwal, Rakhee; Ali, Nawab

    2010-04-01

    Inositol polyphosphates (InsPs) are naturally occurring compounds ubiquitously present in plants and animals. Inositol hexakisphosphate (InsP6) is the most abundant among all InsPs and constitutes the major portion of dietary fiber in most cereals, legumes and nuts. Certain derivatives of InsPs also regulate cellular signaling mechanisms. InsPs have also been shown to reduce tumor formation and induce apoptosis in cancerous cells. Therefore, in this study, the effects of InsPs on apoptosis were studied in an attempt to investigate their potential anti-cancer therapeutic application and understand their mechanism of action. Acridine orange and ethidium bromide staining suggested that InsP6 dose dependently induced apoptosis in human breast adenocarcinoma MCF-7 cells. Among InsPs tested (InsP3, InsP4, InsP5, and InsP6), InsP6 was found to be the most effective in inducing apoptosis. Furthermore, effects of InsP6 were found most potent inducing apoptosis. Etoposide, the drug known to induce apoptosis in both in vivo and in vitro, was used as a positive control. Western blotting experiments using specific antibodies against known apoptotic markers suggested that InsP6 induced apoptotic changes were mediated via an intrinsic apoptotic pathway.

  13. Determination of myo-inositol hexakisphosphate (phytate) in urine by inductively coupled plasma atomic emission spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Grases, F.; Perello, J.; Isern, B.; Prieto, R.M

    2004-05-10

    Myo-inositol hexakisphosphate (phytate) is a substance present in urine with an important role in preventing calcium renal calculi development. In spite of this, the use of urinary phytate levels on stone-formers' evaluation and treatment is still notably restricted as a consequence of the enormous difficulty to analyze this substance in urine. In this paper, a simple procedure for routinary urinary phytate determination based on phosphorus determination through inductively coupled plasma atomic emission spectrometry is described. The method only requires a previous separation of phytate from other components by column anion exchange chromatography. The working linear range used was 0-2 mg l{sup -1} phosphorus (0-7 mg l{sup -1} phytate). The limit of detection was 64 {mu}g l{sup -1} of phytate and the limit of quantification was 213 {mu}g l{sup -1}. The relative standard deviation (R.S.D.) for 1.35 mg l{sup -1} phytate was 2.4%. Different urine samples were analyzed using an alternative analytical methodology based on gas chromatography (GC)/mass detection used for inositol determination (phytate was previously hydrolyzed), resulting both methods comparable using as criterion to assess statistical significance P<0.05.

  14. Kinetic crystallization separation process of the inositol isomers by controlling metastable zones

    Science.gov (United States)

    Konuki, Kaname; Hirasawa, Izumi

    2013-06-01

    D-chiro-inositol (DCI) is prepared by the immobilized enzyme reaction which uses myo-inositol (MI) as the substrate and the conversion rate is about 13%. The aim of this study was to develop a separation method for high purity DCI crystals from a reaction solution including low purity DCI only by the crystallization process. We succeeded in separating DCI crystals of 96% purity by water cooling crystallization, but it was presumed that scale-up was difficult. Although we tried anti-solvent crystallization similar to water cooling crystallization, high purity DCI crystals were not obtained. Therefore, we proposed the crystallization separation process by controlling metastable zones. The purity of a desired compound is controlled by this process, because solid-liquid separation is achieved before crystallization of compound in metastable zone. By the crystallization using this method, the DCI crystals of 97% purity were obtained. Although the yield per batch is about 50%, the actual yield is improved as the last mother liquor returns into the process of the following batch. When this process was repeated, the purity and the yield of DCI were reproduced and the robustness of this process was proved. It is expected that scale-up of this process will be successful, and this purification method could be applicable to similar systems such as separation of isomers and analogs.

  15. Potentiometric and spectroscopic study of the interaction of 3d transition metal ions with inositol hexakisphosphate

    Science.gov (United States)

    Veiga, Nicolás; Macho, Israel; Gómez, Kerman; González, Gabriel; Kremer, Carlos; Torres, Julia

    2015-10-01

    Among myo-inositol phosphates, the most abundant in nature is the myo-inositol hexakisphosphate, InsP6. Although it is known to be vital to cell functioning, the biochemical research into its metabolism needs chemical and structural analysis of all the protonation, complexation and precipitation processes that it undergoes in the biological media. In view of its high negative charge at physiological level, our group has been leading a thorough research into the InsP6 chemical and structural behavior in the presence of the alkali and alkaline earth metal ions essential for life. The aim of this article is to extend these studies, dealing with the chemical and structural features of the InsP6 interaction with biologically relevant 3d transition metal ions (Fe(II), Fe(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)), in a non-interacting medium and under simulated physiological conditions. The metal-complex stability constants were determined by potentiometry, showing under ligand-excess conditions the formation of mononuclear species in different protonation states. Under metal ion excess, polymetallic species were detected for Fe(II), Fe(III), Zn(II) and Cu(II). Additionally, the 31P NMR and UV-vis spectroscopic studies provided interesting structural aspects of the strong metal ion-InsP6 interaction.

  16. INOSITOL HEXAKISPHOSPHATE MEDIATES APOPTOSIS IN HUMAN BREAST ADENOCARCINOMA MCF-7 CELL LINE VIA INTRINSIC PATHWAY

    International Nuclear Information System (INIS)

    Agarwal, Rakhee; Ali, Nawab

    2010-01-01

    Inositol polyphosphates (InsP s ) are naturally occurring compounds ubiquitously present in plants and animals. Inositol hexakisphosphate (InsP 6 ) is the most abundant among all InsP s and constitutes the major portion of dietary fiber in most cereals, legumes and nuts. Certain derivatives of InsP s also regulate cellular signaling mechanisms. InsP s have also been shown to reduce tumor formation and induce apoptosis in cancerous cells. Therefore, in this study, the effects of InsPs on apoptosis were studied in an attempt to investigate their potential anti-cancer therapeutic application and understand their mechanism of action. Acridine orange and ethidium bromide staining suggested that InsP 6 dose dependently induced apoptosis in human breast adenocarcinoma MCF-7 cells. Among InsP s tested (InsP 3 , InsP 4 , InsP 5 , and InsP 6 ), InsP 6 was found to be the most effective in inducing apoptosis. Furthermore, effects of InsP 6 were found most potent inducing apoptosis. Etoposide, the drug known to induce apoptosis in both in vivo and in vitro, was used as a positive control. Western blotting experiments using specific antibodies against known apoptotic markers suggested that InsP 6 induced apoptotic changes were mediated via an intrinsic apoptotic pathway.

  17. Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study.

    Science.gov (United States)

    Yaman, Ferhan; Acikan, Izzet; Dundar, Serkan; Simsek, Sercan; Gul, Mehmet; Ozercan, Ibrahim Hanifi; Komorowski, James; Sahin, Kazim

    2016-01-01

    Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25%) is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P0.05). ASI supplementation significantly improved bone tissue healing in rats with critical-sized defects. This study demonstrated that ASI can enhance bone repair and has potential as a therapeutic regimen in humans.

  18. Understanding the factors that determine registered nurses' turnover intentions.

    Science.gov (United States)

    Osuji, Joseph; Uzoka, Faith-Michael; Aladi, Flora; El-Hussein, Mohammed

    2014-01-01

    Turnover among registered nurses (RNs) produces a negative impact on the health outcomes of any health care organization. It is also recognized universally as a problem in the nursing profession. Little is known about the turnover intentions and career orientations of RNs working in Calgary, Alberta, Canada. The aim of this study is to contribute to the knowledge of and to advance the discussion on the turnover of nursing professionals. The study population consisted of RNs employed in the five major hospitals in Calgary. There were 193 surveys returned, representing a response rate of 77.2%. The results show that age and education have a negative effect on turnover intention. Education was found to have a significant negative effect on career satisfaction but not on job satisfaction and organizational commitment. Length of service has a significant negative effect on turnover intention. Role ambiguity has significant highly negative effect on career satisfaction. Growth opportunity and supervisor support have a very significant positive effect on job satisfaction, career satisfaction, and organizational commitment. External career opportunities and organizational commitment do not seem to have a significant effect on turnover intention. Career satisfaction, on the other hand, had negative significant effects on turnover intention.

  19. Measurements of protein turnover in man with nitrogen-15

    International Nuclear Information System (INIS)

    Garlick, P.J.; Waterlow, J.C.

    1977-01-01

    Past and present methods of measuring total body protein turnover with 15 N-labelled compounds are reviewed, and a short assessment made of results achieved. Protein turnover in man was first measured by Sprinson and Rittenberg (1949) using 15 N glycine as tracer. The rate of turnover was calculated from the fraction of the dose excreted in urine in the days following a single oral dose of the isotope. In the following years a number of similar methods were devised but interest waned, perhaps because consistent changes in turnover rate under different conditions were not detected. A revival of interest came with the measurement of changes in protein turnover in malnourished and recovering children by Picou and Taylor-Roberts (1969). Nitrogen-15-glycine was infused and measurements were made of the abundance of 15 N in urinary urea, which reached a plateau in about 24 hours. Turnover rates were calculated from the proportion of the infused dose excreted in urea after the plateau had been reached. This method has also been used successfully on adults when the isotope has been given as three-hourly oral doses. In adults, however, plateau labelling in urea is not usually reached for two days. In our laboratory the use of urinary ammonia, which reaches a plateau more quickly than urea, has been examined. In addition, comparisons have been made between constant infusion and single dose of isotope. Halliday and McKeran (1975) infused 15 N-lysine and measured the 15 N abundance in the free lysine of plasma, which reached a plateau in about 12 hours. Turnover in the whole body and turnover of muscle proteins and of plasma albumin were estimated separately. These methods of measuring protein turnover with 15 N are described and results reviewed of the effects of food intake, nutritional status and age. (author)

  20. Employee turnover and productivity among small business entities in Nigeria

    Directory of Open Access Journals (Sweden)

    John N. N. Ugoani

    2016-12-01

    Full Text Available This study was designed to evaluate the problems of employee turnover on productivity among small business entities in Nigeria, and recommend remedial actions. Employee turnover is the separation of employees from employers and replacement with other employees. Productive manpower is a critical element for the economic survival of any small business entity. The survey research design was used for the study. The sample comprised of 320 respondents. Data generated were analyzed by using descriptive, and Z-test statistical techniques. It was found that employee turnover adversely affects productivity in small business entities.

  1. Colloidal 234Th and the turnover of oceanic DOC

    International Nuclear Information System (INIS)

    Murray, J.W.; Balistrieri, L.S.

    1994-01-01

    234 Th has been proposed to be a tracer for the labile, colloidal fraction of DOC in seawater. During the recent North Atlantic Bloom Experiment (NABE) the turnover of DOC was directly measured. 234 Th and total suspended matter (C p ) were also measured by different research groups. Using the NABE 234 Th data the authors have calculated the turnover rate of colloidal material using the Brownian Pumping model of Honeyman and Santschi and the 4-box particle cycling model of Moran and Buesseler. The rate constants for colloid cycling determined from the 234 Th data agree well with the experimentally determined rate constants for turnover of DOC

  2. Turnover and employment in the German wind energy industry

    International Nuclear Information System (INIS)

    Keuper, A.

    1995-01-01

    Results of the fast growing wind energy market in 1994 are the turnover reaching more than 800 million DM, and the number of employees to about 3,700. In 1995 the manufacturers expect to need less than 4 employees to build and to install 1 MW rated power and to decrease the ratio of manufacturer's turnover per installed power unit to about 1900 DM/kW. In spite of this development it is expected that the turnover and the number of employees will increase due to the still fast growing market. (orig.)

  3. The Influence of Job Satisfaction on Employee Turnover

    OpenAIRE

    Krempl, Jan

    2016-01-01

    This Master's Thesis deals with the topics of employee turnover and job satisfaction, more precisely with the way in which job satisfaction can influence employee turnover in a company. The goal of the Thesis is to design a way to analyse job satisfaction in an organization and determine the way in which job satisfaction influences the turnover potential of current employees. The Thesis is divided into three main chapters. The first chapter is a literary research that deals with topics of emp...

  4. Sildenafil Stimulates Aqueous Humor Turnover in Rabbits

    Science.gov (United States)

    Alvarez, Lawrence J.; Zamudio, Aldo C.; Candia, Oscar A.

    2013-01-01

    Sildenafil citrate increases ocular blood flow and accelerates the rate of anterior chamber refilling after paracentesis. The latter effect could have resulted from a reduction in outflow facility or from an increase in aqueous humor (AH) production. In this study, we used scanning ocular fluorophotometry to examine the effects of sildenafil on AH turnover, and thus, AH production in eyes of live normal rabbits. For this, the rate of aqueous humor flow (AHF) was quantified with a commercially available fluorophotometer that measured the rate of fluorescein clearance from the anterior segment, which predominantly occurs via the trabecular meshwork. After ≈ 2 hrs of control scans to determine the baseline rate of AHF, the rabbits were fed 33 mg of sildenafil and allowed ≈ 45 min for the drug to enter the systemic circulation. Thereafter, fluorescence scans were retaken for an additional 90–120 min. Sildenafil ingestion increased AHF by about 36%, from 2.31 μL/min to 3.14 μL/min (PViagra, Revatio), stimulates AHF in rabbits. Our results seem consistent with reports indicating that the drug dilates intraocular arteries and augments intraocular vascular flow. These physiological responses to the agent apparently led to increased fluid entry into the anterior chamber. As such, the drug might have utility in patients with ocular hypotony resulting from insufficient AH formation. PMID:23562660

  5. Quantification of myo-inositol, 1,5-anhydro- D-sorbitol, and D-chiro-inositol using high-performance liquid chromatography with electrochemical detection in very small volume clinical samples.

    Science.gov (United States)

    Schimpf, Karen J; Meek, Claudia C; Leff, Richard D; Phelps, Dale L; Schmitz, Daniel J; Cordle, Christopher T

    2015-11-01

    Inositol is a six-carbon sugar alcohol and is one of nine biologically significant isomers of hexahydroxycyclohexane. Myo-inositol is the primary biologically active form and is present in higher concentrations in the fetus and newborn than in adults. It is currently being examined for the prevention of retinopathy of prematurity in newborn preterm infants. A robust method for quantifying myo-inositol (MI), D-chiro-inositol (DCI) and 1,5-anhydro- D-sorbitol (ADS) in very small-volume (25 μL) urine, blood serum and/or plasma samples was developed. Using a multiple-column, multiple mobile phase liquid chromatographic system with electrochemical detection, the method was validated with respect to (a) selectivity, (b) accuracy/recovery, (c) precision/reproducibility, (d) sensitivity, (e) stability and (f) ruggedness. The standard curve was linear and ranged from 0.5 to 30 mg/L for each of the three analytes. Above-mentioned performance measures were within acceptable limits described in the Food and Drug Administration's Guidance for Industry: Bioanalytical Method Validation. The method was validated using blood serum and plasma collected using four common anticoagulants, and also by quantifying the accuracy and sensitivity of MI measured in simulated urine samples recovered from preterm infant diaper systems. The method performs satisfactorily measuring the three most common inositol isomers on 25 μL clinical samples of serum, plasma, milk, and/or urine. Similar performance is seen testing larger volume samples of infant formulas and infant formula ingredients. MI, ADS and DCI may be accurately tested in urine samples collected from five different preterm infant diapers if the urine volume is greater than 2-5 mL. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Alpha 1A and alpha 1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex

    NARCIS (Netherlands)

    Michel, M. C.; Büscher, R.; Philipp, T.; Brodde, O. E.

    1993-01-01

    We have studied the role of alpha 1A- and alpha 1B-adrenoceptors in noradrenaline- and methoxamine-stimulated inositol phosphate accumulation in rat renal cortical slices. [3H]Prazosin binding studies with and without inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment suggested

  7. The Vip1 inositol polyphosphate kinase family regulates polarized growth and modulates the microtubule cytoskeleton in fungi.

    Directory of Open Access Journals (Sweden)

    Jennifer Pöhlmann

    2014-09-01

    Full Text Available Microtubules (MTs are pivotal for numerous eukaryotic processes ranging from cellular morphogenesis, chromosome segregation to intracellular transport. Execution of these tasks requires intricate regulation of MT dynamics. Here, we identify a new regulator of the Schizosaccharomyces pombe MT cytoskeleton: Asp1, a member of the highly conserved Vip1 inositol polyphosphate kinase family. Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. Importantly, our analysis of the in vitro kinase activities of various S. pombe Asp1 variants demonstrated that the C-terminal phosphatase-like domain of the dual domain Vip1 protein negatively affects the inositol pyrophosphate output of the N-terminal kinase domain. These data suggest that the former domain has phosphatase activity. Remarkably, Vip1 regulation of the MT cytoskeleton is a conserved feature, as Vip1-like proteins of the filamentous ascomycete Aspergillus nidulans and the distantly related pathogenic basidiomycete Ustilago maydis also affect the MT cytoskeleton in these organisms. Consistent with the role of interphase MTs in growth zone selection/maintenance, all 3 fungal systems show aspects of aberrant cell morphogenesis. Thus, for the first time we have identified a conserved biological process for inositol pyrophosphates.

  8. Inositol-1-phosphate synthetase mRNA as a new target for antisense inhibition of Mycobacterium tuberculosis.

    Science.gov (United States)

    Li, Yuanyuan; Chen, Zhifei; Li, Xiaobo; Zhang, Hongling; Huang, Qiang; Zhang, Ying; Xu, Shunqing

    2007-03-10

    The need for novel antimicrobial agents to combat the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis is a worldwide urgency. This study has investigated the effects on phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of inositol-1-phosphate synthase, the key enzyme in the first step in inositol synthesis. Inositol is utilized by M. tuberculosis in the production of its major thiol, which is an antioxidant that helps M. tuberculosis to get rid of reactive oxygen species and electrophilic toxins. Real-time RT-PCR analysis revealed that mRNA expression of inositol-1-phosphate (I-1-P) synthase was significantly reduced upon addition of 20 microM PS-ODNs. Treatment with antisense PS-ODNs also reduced the level of mycothiol and the proliferation of M. tuberculosis and enhanced susceptibility to antibiotics. The experiments indicated that the antisense PS-ODNs could enter the cytoplasm of M. tuberculosis and inhibit the expression of I-1-P synthase. This study demonstrates that the M. tuberculosis I-1-P synthase is a target for the development of novel antibiotics and PS-ODN to I-1-P synthase is a promising antimycobaterial candidate.

  9. Involvement of inositol biosynthesis and nitric oxide in the mediation of UV-B induced oxidative stress

    Directory of Open Access Journals (Sweden)

    Dmytro I Lytvyn

    2016-04-01

    Full Text Available The involvement of NO-signaling in ultraviolet B (UV-B induced oxidative stress in plants is an open question. Inositol biosynthesis contributes to numerous cellular functions, including the regulation of plants tolerance to stress. This work reveals the involvement of inositol-3-phosphate synthase 1 (IPS1, a key enzyme for biosynthesis of myo-inositol and its derivatives, in the response to NO-dependent oxidative stress in Arabidopsis. Homozygous mutants deficient for IPS1 (atips1 and wild-type plants were transformed with a reduction-oxidation-sensitive green fluorescent protein 2 (grx1-rogfp2 and used for the dynamic measurement of UV-B-induced and SNP (sodium nitroprusside-mediated oxidative stresses by confocal microscopy. atips1 mutants displayed greater tissue-specific resistance to the action of UV-B than the wild type. SNP can act both as an oxidant or repairer depending on the applied concentration, but mutant plants were more tolerant than the wild type to nitrosative effects of high concentration of SNP. Additionally, pretreatment with low concentrations of SNP (10, 100 μM before UV-B irradiation resulted in a tissue-specific protective effect that was enhanced in atips1. We conclude that the interplay between nitric oxide and inositol signaling can be involved in the mediation of UV-B-initiated oxidative stress in the plant cell.

  10. 5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus. A pharmacological characterization.

    Science.gov (United States)

    Hoyer, D; Waeber, C; Schoeffter, P; Palacios, J M; Dravid, A

    1989-03-01

    1) 5-HT (5-hydroxytryptamine, serotonin) induces inositol phosphate production in a pig choroid plexus preparation. This effect has been pharmacologically characterized and the data compared to those obtained from radioligand binding studies performed with [3H]mesulergine to 5-HT1C sites in pig choroid plexus membranes. 2) The rank order of potency of agonists stimulating inositol phosphate production was: alpha-methyl-5-HT greater than 1-methyl-5-HT greater than DOI greater than bufotenine = SKF 83566 = 5-HT greater than 5-MeO-DMT greater than 5-MeOT = RU 24969 greater than SCH 23390 greater than 5-CT. 8-OH-DPAT was virtually devoid of activity at 100 mumol/l. 3) The increase in inositol phosphate production induced by 5-HT and other agonists was surmountably antagonised by mesulergine, ketanserin and spiperone with pKB values of 8.7, 6.7 and 5.3, respectively. 4) The rank order of potency of antagonists was: metergoline greater than mesulergine greater than LY 53857 greater than ritanserin greater than methiothepin greater than mianserin greater than cyproheptadine greater than pirenperone greater than cinanserin greater than ketanserin greater than spiperone. The following antagonists were virtually devoid of activity at 100 mumol/l; pindolol, 21-009 and yohimbine. 5) The results obtained both with agonists and antagonists strongly support the view that 5-HT1C receptors mediate agonist induced production of inositol phosphates in pig choroid plexus.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Maternal myo-inositol, glucose, and zinc status is associated with the risk of offspring with spina bifida.

    NARCIS (Netherlands)

    Groenen, P.; Peer, P.G.M.; Wevers, R.A.; Swinkels, D.W.; Franke, B.; Mariman, E.C.M.; Steegers-Theunissen, R.P.M.

    2003-01-01

    OBJECTIVE: The purpose of this study was to investigate the maternal and children's myo-inositol, glucose, and zinc status in association with spina bifida risk. STUDY DESIGN: Sixty-three mothers and 70 children with spina bifida and 102 control mothers and 85 control children were investigated. The

  12. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature.

    Science.gov (United States)

    Regidor, Pedro-Antonio; Schindler, Adolf Eduard; Lesoine, Bernd; Druckman, Rene

    2018-03-02

    Introduction The use of 2 × 2000 mg myo-inositol +2 × 200 μg folic acid per day is a safe and promising tool in the effective improvement of symptoms and infertility for patients with polycystic ovary syndrome (PCOS). In addition, PCOS is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Typically, PCOS patients suffer of poor quality oocytes. Patients and methods In an open, prospective, non-blinded, non-comparative observational study, 3602 infertile women used myo-inositol and folic acid between 2 and 3 months in a dosage of 2 × 2000 mg myo-inositol +2 × 200 μg folic acid per day. In a subgroup of 32 patients, hormonal values for testosterone, free testosterone and progesterone were analyzed before and after 12 weeks of treatment. The mean time of use was 10.2 weeks. In the second part of this trial it was investigated if the combination of myo-inositol + folic acid was able to improve the oocyte quality, the ratio between follicles and retrieved oocytes, the fertilization rate and the embryo quality in PCOS patients undergoing IVF treatments. Twenty-nine patients with PCOS, underwent IVF protocols for infertility treatment and were randomized prospectively into two groups. Group A (placebo) with 15 patients and group B (4000 mg myo-inositol +400 μg folic acid per day) with 14 patients were evaluated. The patients of group B used 2 months' myo-inositol + folic acid before starting the IVF protocol. For statistically analyses Student's t-test was performed. Results Seventy percent of the women had a restored ovulation, and 545 pregnancies were observed. This means a pregnancy rate of 15.1% of all the myo-inositol and folic acid users. In 19 cases a concomitant medication with clomiphene or dexamethasone was used. One twin pregnancy was documented. Testosterone levels changed from 96.6 ng/mL to 43.3 ng/mL and progesterone from 2.1 ng/mL to 12.3 ng/mL in the mean after 12 weeks of treatment (p

  13. Cyclic AMP counteracts mitogen-induced inositol phosphate generation and increases in intracellular Ca2+ concentrations in human lymphocytes

    NARCIS (Netherlands)

    van Tits, L. J.; Michel, M. C.; Motulsky, H. J.; Maisel, A. S.; Brodde, O. E.

    1991-01-01

    1. The effects of increases in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) on mitogen-induced generation of inositol phosphates and increases in intracellular Ca2+ concentration were investigated in human peripheral blood mononuclear leukocytes (MNL). 2. The mitogens concanavalin

  14. Metabolomics Reveals Relationship between Plasma Inositols and Birth Weight: Possible Markers for Fetal Programming of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Pia Marlene Nissen

    2011-01-01

    Full Text Available Epidemiological studies in man and with experimental animal models have shown that intrauterine growth restriction (IUGR resulting in low birth weight is associated with higher risk of programming welfare diseases in later life. In the pig, severe IUGR occurs naturally and contribute substantially to a large intralitter variation in birth weight and may therefore be a good model for man. In the present paper the natural form of IUGR in pigs was studied close to term by nuclear magnetic resonance (NMR-based metabolomics. The NMR-based investigations revealed different metabolic profiles of plasma samples from low-birth weight (LW and high-birth weight (HW piglets, respectively, and differences were assigned to levels of glucose and myo-inositol. Further studies by GC-MS revealed that LW piglets had a significant higher concentration of myoinositol and D-chiro-inositol in plasma compared to larger littermates. Myo-inositol and D-chiro-inositol have been coupled with glucose intolerance and insulin resistance in adults, and the present paper therefore suggests that IUGR is related to impaired glucose metabolism during fetal development, which may cause type 2 diabetes in adulthood.

  15. Raman spectra of organic (myo-inositol hexakis phosphate) and inorganic P sepctra show pH dependence

    Science.gov (United States)

    Understanding phosphorous fate and transport is in part limited by technical difficulties and/or access to expensive equipment associated with differentiating ortho-phosphate (P) from organic phosphate in complex environmental samples. Myo-inositol hexakis phosphate (IHP) is the most prevalent form...

  16. Comparison of alpha 1A- and alpha 1B-adrenoceptor coupling to inositol phosphate formation in rat kidney

    NARCIS (Netherlands)

    Büscher, R.; Erdbrügger, W.; Philipp, T.; Brodde, O. E.; Michel, M. C.

    1994-01-01

    We have compared the coupling mechanisms of rat renal alpha 1A- and alpha 1B-like adrenoceptors to inositol phosphate formation. The experiments were performed in parallel in native renal tissue preparations and in those where alpha 1B-adrenoceptors had been inactivated by treatment with 10 mumol/l

  17. Supplementation of plant-based diets for rainbow trout, Oncorhynchus mykiss with macro-minerals and inositol.

    Science.gov (United States)

    Replacement of fish meal with plant products in aquafeeds results in the elimination of dietary compounds which may be important for optimal growth and physiology. A study was conducted to determine if supplementation with macro-minerals and/or inositol would improve performance of rainbow trout fe...

  18. Isolation of 1-monomethylphosphoinositol 4,5-bisphosphate [a product of methanolysis of inositol 1,2-(cyclic)-4,5-trisphosphate] from Swiss mouse 3T3 cells

    International Nuclear Information System (INIS)

    Lips, D.L.; Bross, T.E.; Majerus, P.W.

    1988-01-01

    We have noted two previously undescribed inositol polyphosphates in neutral methanol extracts from Swiss mouse 3T3 cells that were grown in [ 3 H]inositol and stimulated with platelet-derived growth factor. They have been identified as 1-monomethylphosphoinositol 4,5-bisphosphate and 1-monomethylphosphoinositol 4-phosphate by comparison to a synthesized standard using HPLC chromatography, paper electrophoresis, and enzymatic dephosphorylation with inositol polyphosphate 5-phosphomonoesterase and intestinal alkaline phosphatase. We propose that these compounds are formed by methanolysis of inositol 1,2-(cyclic)-4,5-trisphosphate and inositol 1,2-(cyclic)-4-bisphosphate present in the cells. Inositol cyclic phosphates did not react with neutral methanol in the absence of the cells, which are required for the methanolysis reaction. These findings suggest a role for inositol cyclic phosphates as reactive compounds that are added to as yet unidentified cellular acceptors

  19. Parenteral Nutrition and Lipids.

    Science.gov (United States)

    Raman, Maitreyi; Almutairdi, Abdulelah; Mulesa, Leanne; Alberda, Cathy; Beattie, Colleen; Gramlich, Leah

    2017-04-14

    Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them.

  20. 4-hydroxyphenylacetic acid derivatives of inositol from dandelion (Taraxacum officinale) root characterised using LC-SPE-NMR and LC-MS techniques.

    Science.gov (United States)

    Kenny, O; Smyth, T J; Hewage, C M; Brunton, N P; McLoughlin, P

    2014-02-01

    The combination of hyphenated techniques, LC-SPE-NMR and LC-MS, to isolate and identify minor isomeric compounds from an ethyl acetate fraction of Taraxacum officinale root was employed in this study. Two distinct fractions of 4-hydroxyphenylacetic acid derivatives of inositol were isolated and characterised by spectroscopic methods. The (1)H NMR spectra and MS data revealed two groups of compounds, one of which were derivatives of the di-4-hydroxyphenylacetic acid derivative of the inositol compound tetrahydroxy-5-[2-(4-hydroxyphenyl)acetyl] oxycyclohexyl-2-(4-hydroxyphenyl) acetate, while the other group consisted of similar tri-substituted inositol derivatives. For both fractions the derivatives of inositols vary in the number of 4-hydroxyphenylacetic acid groups present and their position and geometry on the inositol ring. In total, three di-substituted and three tri-substituted 4-hydroxyphenylacetic acid inositol derivates were identified for the first time along with a further two previously reported di-substituted inositol derivatives. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Preventive and Therapeutic Role of Dietary Inositol Supplementation in Periconceptional Period and During Pregnancy: A Summary of Evidences and Future Applications.

    Science.gov (United States)

    Noventa, Marco; Vitagliano, Amerigo; Quaranta, Michela; Borgato, Shara; Abdulrahim, Baydaa; Gizzo, Salvatore

    2016-03-01

    Although inositol dietary deficiency in the general population has not been demonstrated at the serum level, several findings are emerging regarding the impact of inositol supplementation in periconceptional period and in early phases of pregnancy. We are aimed to summarize all experimental (murine in vivo and in vitro murine embryo studies) and clinical (human) evidences regarding the role of inositol in the prevention and treatment of folate-resistant embryo neural tube defects (FR-NTDs) and gestational diabetes mellitus (GDM). We also collected all information regarding the effect that inositol supplementation may have in the metabolic reassessment of early and late pregnancy in order to draw evidence-based conclusions and suggest further studies defining the potential therapeutic role of this molecule in human reproduction. The systematic review of literature clearly showed that inositol supplementation in preconceptional period and in early phase of pregnancy reduces the risk of developing GDM in patients at increased risk. Furthermore, continued intake during pregnancy improves the metabolic status of affected patients, but further studies are needed to confirm this end point. All women at risk of FR-NTDs assuming inositol from the periconceptional period until late pregnancy are reported to have healthy newborns without any significant complications linked to inositol supplementation. © The Author(s) 2015.

  2. Turnover of grain legume N rhizodeposits and effect of rhizodeposition on the turnover of crop residues

    DEFF Research Database (Denmark)

    Mayer, J.; Buegger, F.; Jensen, E.S.

    2004-01-01

    C). A sandy loam soil for the experiment was either stored at 6 degreesC or planted with the respective grain legume in pots. Legumes were in situ N-15 stem labelled during growth and visible roots were removed at maturity. The remaining plant-derived N in soil was defined as N rhizodeposition....... In the experiment the turnover of C and N was compared in soils with and without previous growth of three legumes and with and without incorporation of crop residues. After 168 days, 21% (lupin), 26% (faba bean) and 27% (pea) of rhizodeposition N was mineralised in the treatments without crop residues. A smaller...

  3. Uncoupling of attenuated myo-[3H]inositol uptake and dysfunction in Na(+)-K(+)-ATPase pumping activity in hypergalactosemic cultured bovine lens epithelial cells

    International Nuclear Information System (INIS)

    Cammarata, P.R.; Tse, D.; Yorio, T.

    1991-01-01

    Attenuation of both the active transport of myo-inositol and Na(+)-K(+)-ATPase pumping activity has been implicated in the onset of sugar cataract and other diabetic complications in cell culture and animal models of the disease. Cultured bovine lens epithelial cells (BLECs) maintained in galactose-free Eagle's minimal essential medium (MEM) or 40 mM galactose with and without sorbinil for up to 5 days were examined to determine the temporal effects of hypergalactosemia on Na(+)-K(+)-ATPase and myo-inositol uptake. The Na(+)-K(+)-ATPase pumping activity after 5 days of continuous exposure to galactose did not change, as demonstrated by 86Rb uptake. The uptake of myo-[3H]inositol was lowered after 20 h of incubation in galactose and remained below that of the control throughout the 5-day exposure period. The coadministration of sorbinil to the galactose medium normalized the myo-[3H]inositol uptake. No significant difference in the rates of passive efflux of myo-[3H]inositol or 86Rb from preloaded galactose-treated and control cultures was observed. Culture-media reversal studies were also carried out to determine whether the galactose-induced dysfunction in myo-inositol uptake could be corrected. BLECs were incubated in galactose for 5 days, then changed to galactose-free physiological medium with and without sorbinil for a 1-day recovery period. myo-Inositol uptake was reduced to 34% of control after 6 days of continuous exposure to galactose. Within 24 h of media reversal, myo-inositol uptake returned to or exceeded control values in BLECs switched to either MEM or MEM with sorbinil.2+ reversible and occurred independently of changes in Na(+)-K(+)-ATPase pumping activity in cultured lens epithelium, indicating that the two parameters are not strictly associated and that the deficit in myo-inositol uptake occurs rapidly during hypergalactosemia

  4. Uncoupling of attenuated myo-(3H)inositol uptake and dysfunction in Na(+)-K(+)-ATPase pumping activity in hypergalactosemic cultured bovine lens epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Cammarata, P.R.; Tse, D.; Yorio, T. (Department of Anatomy, Texas College of Osteopathic Medicine/University of North Texas, Fort Worth (USA))

    1991-06-01

    Attenuation of both the active transport of myo-inositol and Na(+)-K(+)-ATPase pumping activity has been implicated in the onset of sugar cataract and other diabetic complications in cell culture and animal models of the disease. Cultured bovine lens epithelial cells (BLECs) maintained in galactose-free Eagle's minimal essential medium (MEM) or 40 mM galactose with and without sorbinil for up to 5 days were examined to determine the temporal effects of hypergalactosemia on Na(+)-K(+)-ATPase and myo-inositol uptake. The Na(+)-K(+)-ATPase pumping activity after 5 days of continuous exposure to galactose did not change, as demonstrated by 86Rb uptake. The uptake of myo-(3H)inositol was lowered after 20 h of incubation in galactose and remained below that of the control throughout the 5-day exposure period. The coadministration of sorbinil to the galactose medium normalized the myo-(3H)inositol uptake. No significant difference in the rates of passive efflux of myo-(3H)inositol or 86Rb from preloaded galactose-treated and control cultures was observed. Culture-media reversal studies were also carried out to determine whether the galactose-induced dysfunction in myo-inositol uptake could be corrected. BLECs were incubated in galactose for 5 days, then changed to galactose-free physiological medium with and without sorbinil for a 1-day recovery period. myo-Inositol uptake was reduced to 34% of control after 6 days of continuous exposure to galactose. Within 24 h of media reversal, myo-inositol uptake returned to or exceeded control values in BLECs switched to either MEM or MEM with sorbinil.2+ reversible and occurred independently of changes in Na(+)-K(+)-ATPase pumping activity in cultured lens epithelium, indicating that the two parameters are not strictly associated and that the deficit in myo-inositol uptake occurs rapidly during hypergalactosemia.

  5. Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study.

    Science.gov (United States)

    Rago, R; Marcucci, I; Leto, G; Caponecchia, L; Salacone, P; Bonanni, P; Fiori, C; Sorrenti, G; Sebastianelli, A

    2015-01-01

    The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS.

  6. Global Distribution of Root Turnover in Terrestrial Ecosystems

    Data.gov (United States)

    National Aeronautics and Space Administration — Estimates of root turnover rates were calculated from measurements of live root standing crop and belowground net primary production (BNPP) compiled from the primary...

  7. Job turnover and regional attrition among physiotherapists in northern Ontario.

    Science.gov (United States)

    Noh, S; Beggs, C E

    1993-01-01

    Results of an initial study indicated that the most significant factor affecting retention for Physiotherapists in Northern Ontario was perceived opportunity for career development. A follow-up study was completed two years later to determine: 1) actual job turnover and regional attrition among physiotherapists in Northern Ontario; and 2) the predictive validity of variables identified in the first study regarding job turnover and regional attrition. Job turnover occurred in 29.5% of those sampled and the regional attrition rate was 12%. Discriminant function analysis revealed factors affecting job turnover and regional attrition including professional experience, practice location, opportunity for career development and size of community of residence. Based on previous intention, indicated by participants, follow-up revealed that the initial study correctly predicted 77.5% of those who changed their jobs and 74.1% of those who left Northern Ontario. Identified factors provide direction for the development of strategies for recruitment and retention of physiotherapists.

  8. Protein turnover in children studied using 15N

    International Nuclear Information System (INIS)

    Pencharz, P.B.

    1983-01-01

    In 12 neonates the effect of the route of feeding on protein turnover rates was studied, and in 8 children suffering from cystic fibrosis the effect of nutritional rehabilitation on the protein metabolism was examined

  9. Report: Remedial Project Manager Turnover at Superfund Sites

    Science.gov (United States)

    Report #2001-M-000015, June 15, 2001. We determined that EPA Region III did not have formal procedures in place to mitigate continuity problems caused by turnover of EPA personnel in the Superfund program.

  10. Autoradiographic imaging of phosphoinositide turnover in the brain

    International Nuclear Information System (INIS)

    Hwang, P.M.; Bredt, D.S.; Snyder, S.H.

    1990-01-01

    With [ 3 H]cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product [ 3 H]cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways

  11. Global Distribution of Root Turnover in Terrestrial Ecosystems

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: Estimates of root turnover rates were calculated from measurements of live root standing crop and belowground net primary production (BNPP) compiled from...

  12. Wind energy industry in Germany. Turnover and employment

    International Nuclear Information System (INIS)

    Keuper, A.; Schmidt, A.

    1994-01-01

    As a consequence of the growing wind energy market in Germany the importance of the industry in this business are has grown. In 1994 the turnover will go beyond 500 million DM, and the number of employees will reach 2,900. The turnover and the number of employees are increasing in spite of the higher efficiency. In 1994 only 5 employees are needed by a manufacturer to install 1 MW rated power instead of 15 in 1989, and the ratio of installed power to manufacturer's turnover has risen from 0,25 W/DM in 1988 to 0,455 W/DM in 1994. On the other hand the turnover of the manufacturers per employee has increased from 80,000 DM in 1988 to 440,000 DM in 1994. Economic development has considerably been advanced by subsidies for the application of wind energy technology. (orig.)

  13. [A predictive model on turnover intention of nurses in Korea].

    Science.gov (United States)

    Moon, Sook Ja; Han, Sang Sook

    2011-10-01

    The purpose of this study was to propose and test a predictive model that could explain and predict Korean nurses' turnover intentions. A survey using a structured questionnaire was conducted with 445 nurses in Korea. Six instruments were used in this model. The data were analyzed using SPSS 15.0 and Amos 7.0 program. Based on the constructed model, organizational commitment, and burnout were found to have a significant direct effect on turnover intention of nurses. In addition, factors such as empowerment, job satisfaction, and organizational commitment were found to indirectly affect turnover intention of nurse. The final modified model yielded χ²=402.30, pturnover intention in Korean nurses. Findings from this study can be used to design appropriate strategies to further decrease the nurses' turnover intention in Korea.

  14. Rationale for the evaluation of trabecular bone turnover

    International Nuclear Information System (INIS)

    Kimmel, D.B.; Jee, W.S.S.

    1976-01-01

    A procedure for the morphometric evaluation of trabecular bone is identified. Its scrupulous use allows total identification of bone formation and resorption rates, items necessary for the direct histologic analysis of bone turnover

  15. Influence of Religiosity on Turnover Intention: Empirical Evidence ...

    African Journals Online (AJOL)

    Influence of Religiosity on Turnover Intention: Empirical Evidence from Selected Employees in Lagos and Ogun States. Elizabeth I. Olowookere, Olujide A. Adekeye, Gbadebo O. Adejumo, Benedict. C. Agoha, Muyiwa A. Sholarin ...

  16. Soy Reduces Bone Turnover Markers in Women During Early Menopause: A Randomized Controlled Trial.

    Science.gov (United States)

    Sathyapalan, Thozhukat; Aye, Mo; Rigby, Alan S; Fraser, William D; Thatcher, Natalie J; Kilpatrick, Eric S; Atkin, Stephen L

    2017-01-01

    Menopausal estrogen loss leads to an increased bone loss. Soy isoflavones can act as selective estrogen receptor modulators, their role in bone turnover is unclear. The primary outcome was assessing changes in plasma bone turnover markers. The secondary outcomes were assessing changes in cardiovascular risk markers including insulin resistance, blood pressure, and lipid profile. We performed a double-blind randomized parallel study in which 200 women within 2 years after the onset of their menopause were randomized to 15 g soy protein with 66 mg isoflavone (SPI) or 15 g soy protein alone (SP), daily for 6 months. There was a significant reduction in type I collagen crosslinked beta C-telopeptide (βCTX) (bone-resorption marker) with SPI supplementation (0.40 ± 0.17 versus 0.15 ± 0.09 μg/L; p changes in these parameters was observed with SP. There were no significant changes in fasting lipid profile and diastolic blood pressure with either preparation. There was a significant increase in TSH and reduction in free thyroxine (p < 0.01) with SPI supplementation though free tri-iodothyronine was unchanged. In conclusion, soy protein with isoflavones may confer a beneficial effect on bone health, analogous to the mode of action of antiresorptive agents, albeit to a less magnitude. There was a significant improvement of cardiovascular risk markers, but a significant increase in TSH and reduction in free thyroxine after SPI supplementation indicating a detrimental effect on thyroid function. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  17. The efficacy of myo-inositol supplementation to prevent gestational diabetes onset: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, Haifeng; Lv, You; Li, Zhuo; Sun, Lin; Guo, Weiying

    2018-02-06

    The efficacy of myo-inositol supplementation to prevent gestational diabetes onset remains controversial. We conducted a systematic review and meta-analysis to explore the influence of myo-inositol supplementation on the incidence of gestational diabetes. We search PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases through November 2017 for randomized controlled trials (RCTs) assessing the effect of myo-inositol supplementation on gestational diabetes onset. This meta-analysis is performed using the random-effect model. Five randomized controlled trials (RCTs) are included in the meta-analysis. Compared with control group in pregnant women, myo-inositol supplementation is associated with significantly reduced incidence of gestational diabetes (risk ratio (RR) = 0.43; 95%CI = 0.21-0.89; p = .02), and preterm delivery (RR = 0.36; 95%CI = 0.17-0.73; p = .005), but has no substantial impact on 2-h glucose oral glucose tolerance test (OGTT) (mean difference (MD) = -6.90; 95%CI = -15.07 to 1.27; p = .10), gestational age at birth (MD = 0.74; 95%CI = -1.06 to 2.54; p = .42), birth weight (MD = -5.50; 95%CI = -116.99 to 105.99; p = .92), and macrosomia (RR = 0.65; 95%CI = 0.20-2.11; p = .47). Myo-inositol supplementation has some ability to reduce the incidence of gestational diabetes and preterm delivery in pregnant women.

  18. Osmotic regulation and tissue localization of the myo-inositol biosynthesis pathway in tilapia (Oreochromis mossambicus) larvae.

    Science.gov (United States)

    Sacchi, Romina; Gardell, Alison M; Chang, Nicole; Kültz, Dietmar

    2014-10-01

    The myo-inositol biosynthesis (MIB) pathway converts glucose-6-phosphate to the compatible osmolyte myo-inositol, which protects cells from salinity stress. We exposed tilapia larvae just after yolk sac resorption to various hypersaline environments and recorded robust induction of the enzymes that constitute the MIB pathway, myo-inositol-phosphate synthase (MIPS), and inositol monophosphatase 1 (IMPA1). Strong up-regulation of these enzymes is evident at both mRNA (quantitative real-time PCR) and protein (densitometric analysis of Western blots) levels. The highest level of induction of these enzymes occurs at the highest salinity that larvae were exposed to (90 ppt). Less severe salinity stress causes a proportionately reduced induction of the MIB pathway. Two distinct MIPS mRNA variants are present in tilapia larvae and both are induced at comparable levels for all the salinity challenges tested (34, 70, and 90 ppt). Immunohistochemical localization of IMPA1 protein in sagittal sections of salinity stressed and control larvae identified tissues that are particularly potent in inducing the MIB pathway. These tissues include the skin (epidermis), gills, eye (ciliary epithelium) and heart. In particular, the epidermis directly facing the external milieu showed a very strong induction of IMPA1 immunoreactivity. IMPA1 induction in response to salinity stress was not observed in other tissues suggesting that tilapia larvae may also utilize compatible organic osmolytes other than solely myo-inositol for osmoprotection. We conclude that the MIB pathway plays an important role in protecting multiple (but not all) tissues of tilapia larvae from hyperosmotic salinity stress. © 2014 Wiley Periodicals, Inc.

  19. Myo-inositol is a promising treatment for the prevention of ovarian hyperstimulation syndrome (OHSS): an animal study.

    Science.gov (United States)

    Turan, Guluzar Arzu; Eskicioglu, Fatma; Sivrikoz, Oya Nermin; Cengiz, Hakan; Adakan, Saban; Gur, Esra Bahar; Tatar, Sumeyra; Sahin, Nur; Yilmaz, Osman

    2015-11-01

    To evaluate the efficacy of myo-inositol (MI) pretreatment in OHSS. In this experimental OHSS rat model, 42 immature Wistar albino female rats were divided into 6 groups: (1) the control group, (2) the ovarian stimulation group, (3) the OHSS group, (4) the OHSS + Metformin group, (5) OHSS + MI group, (6) OHSS + Metformin + MI group. OHSS was established after treatment with metformin and myo-inositol for 14 days, in the meanwhile the treatment of metformin and myo-inositol was also continued. All animals were killed 48 h after hCG administration and were compared in terms of vascular permeability, ovarian weight and diameter, ovarian VEGF, COX-2 and PEDF expression (immunohistochemistry), serum PEDF and estradiol (E2) levels. Vascular permeability, VEGF and COX-2 expressions were reduced in animals treated with MI and/or metformin. While PEDF expression was increased in the groups taking metformin, there was no difference in PEDF expression in the group taking MI and OHSS group. There was no significant difference in serum PEDF levels between groups. Blood E2 levels were decreased in groups treated with MI or metformin compared to the OHSS group. Our data demonstrate that myo-inositol is effective in preventing OHSS, similar to metformin. Although the two drugs are thought to act through distinct mechanisms, there is no apparent benefit to co-treatment with both drugs in an animal model of OHSS. Administration of myo-inositol prior to IVF treatment may favor the control of ovulation induction. Further studies are necessary to elucidate the mechanism of action and further support our findings.

  20. Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study

    Directory of Open Access Journals (Sweden)

    Yaman F

    2016-06-01

    Full Text Available Ferhan Yaman,1 Izzet Acikan,1 Serkan Dundar,2 Sercan Simsek,3 Mehmet Gul,4 İbrahim Hanifi Ozercan,3 James Komorowski,5 Kazim Sahin6 1Department of Oral-Maxillofacial Surgery, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 2Department of Periodontology, Faculty of Dentistry, Firat University, Elazig, Turkey; 3Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey; 4Department of Periodontology, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 5Nutrition 21, LLC, Purchase, NY, USA; 6Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey Background: Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25% is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. Objective: The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. Methods: The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. Results: Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05. New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05. However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05. Conclusion: ASI supplementation significantly improved bone tissue

  1. A High-Throughput Screening-Compatible Strategy for the Identification of Inositol Pyrophosphate Kinase Inhibitors.

    Directory of Open Access Journals (Sweden)

    Brandi M Baughman

    Full Text Available Pharmacological tools-'chemical probes'-that intervene in cell signaling cascades are important for complementing genetically-based experimental approaches. Probe development frequently begins with a high-throughput screen (HTS of a chemical library. Herein, we describe the design, validation, and implementation of the first HTS-compatible strategy against any inositol phosphate kinase. Our target enzyme, PPIP5K, synthesizes 'high-energy' inositol pyrophosphates (PP-InsPs, which regulate cell function at the interface between cellular energy metabolism and signal transduction. We optimized a time-resolved, fluorescence resonance energy transfer ADP-assay to record PPIP5K-catalyzed, ATP-driven phosphorylation of 5-InsP7 to 1,5-InsP8 in 384-well format (Z' = 0.82 ± 0.06. We screened a library of 4745 compounds, all anticipated to be membrane-permeant, which are known-or conjectured based on their structures-to target the nucleotide binding site of protein kinases. At a screening concentration of 13 μM, fifteen compounds inhibited PPIP5K >50%. The potency of nine of these hits was confirmed by dose-response analyses. Three of these molecules were selected from different structural clusters for analysis of binding to PPIP5K, using isothermal calorimetry. Acceptable thermograms were obtained for two compounds, UNC10112646 (Kd = 7.30 ± 0.03 μM and UNC10225498 (Kd = 1.37 ± 0.03 μM. These Kd values lie within the 1-10 μM range generally recognized as suitable for further probe development. In silico docking data rationalizes the difference in affinities. HPLC analysis confirmed that UNC10225498 and UNC10112646 directly inhibit PPIP5K-catalyzed phosphorylation of 5-InsP7 to 1,5-InsP8; kinetic experiments showed inhibition to be competitive with ATP. No other biological activity has previously been ascribed to either UNC10225498 or UNC10112646; moreover, at 10 μM, neither compound inhibits IP6K2, a structurally-unrelated PP-InsP kinase. Our

  2. Aberrant 3H in Ehrlich mouse ascites tumor cell nucleotides after in vivo labeling with myo-[2-3H]- and L -myo-[1-3H]inositol: implications for measuring inositol phosphate signaling

    DEFF Research Database (Denmark)

    Christensen, Søren C.; Jensen, Annelie Kolbjørn; Simonsen, L.O.

    2003-01-01

    : the oxidative conversion to -glucuronate. In contrast, with the 3H at C2 of myo-inositol, the 3H-C2 passes into the pentose phosphate conversions with resulting labeling of nucleotides. The extent of catabolism to 3H-labeled water, the cellular accumulation of 3H-myo-inositol, the incorporation into cellular...

  3. Turnover of nursing employees in a Gauteng hospital group

    OpenAIRE

    Japie Greyling; Karel Stanz

    2010-01-01

    Orientation: The South African nursing profession is in a crisis as professional nurses leave the country in search of lucrative work overseas. Research purpose: The purpose of this study was to investigate individual determinants of voluntary turnover to identify a risk-group profile. Motivation for the study: Nursing employers should have a clearer understanding of the dynamics around nurses’ turnover behaviour and embark on strategies to retain their talent. Research design, app...

  4. Kramers Turnover Theory for a Triple Well Potential

    International Nuclear Information System (INIS)

    Pollak, E.; Talkner, P.

    2001-01-01

    Kramers turnover theory is solved for a particle in a symmetric triple well potential for temperatures above the crossover temperature between tunneling and activated barrier crossing. Comparison with the turnover theory for a double well potential shows that the presence of the intermediate well always leads to a decrease of the reaction rate. At most though, the rate is a factor of two smaller than in the case of a double well potential. (author)

  5. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  6. Telaah Hubungan Kepuasan Kerja Dan Komitmen Organisasional Terhadap Turnover Intention

    Directory of Open Access Journals (Sweden)

    Ali Amran

    2017-04-01

    ABSTRACT       Employees are the most important resources of company. They are human resources to do and move all of the activities of company. Therefore, company needs to keep and maintain their job satisfaction and organizational commitment in order to reduce the intention to leave the company (turnover intention. It is necessary to study the relationship among job satisfaction, organizational commitment and turnover intention. This will give benefit to determine the important values of employees’ job satisfaction and organizational commitment and its influences on turnover intention. The research methods are descriptive survey and verificative survey that is used to assess the performance of independent variables: those are job satisfaction and organizational commitment,  and dependent variable: that is turnover intention with doing observation to employees of PT. Alexindo Bekasi. The result of this research is there is influence of job satisfaction and organizational commitment on turnover intention. This research is the improvement of existing researches which can be applied in the other companies specially for the human resource or employee behavior field.   Keywords: Job Satisfaction, Organizational Commitment, Turnover Intention

  7. Long-period astronomical forcing of mammal turnover.

    Science.gov (United States)

    van Dam, Jan A; Abdul Aziz, Hayfaa; Alvarez Sierra, M Angeles; Hilgen, Frederik J; van den Hoek Ostende, Lars W; Lourens, Lucas J; Mein, Pierre; van der Meulen, Albert J; Pelaez-Campomanes, Pablo

    2006-10-12

    Mammals are among the fastest-radiating groups, being characterized by a mean species lifespan of the order of 2.5 million years (Myr). The basis for this characteristic timescale of origination, extinction and turnover is not well understood. Various studies have invoked climate change to explain mammalian species turnover, but other studies have either challenged or only partly confirmed the climate-turnover hypothesis. Here we use an exceptionally long (24.5-2.5 Myr ago), dense, and well-dated terrestrial record of rodent lineages from central Spain, and show the existence of turnover cycles with periods of 2.4-2.5 and 1.0 Myr. We link these cycles to low-frequency modulations of Milankovitch oscillations, and show that pulses of turnover occur at minima of the 2.37-Myr eccentricity cycle and nodes of the 1.2-Myr obliquity cycle. Because obliquity nodes and eccentricity minima are associated with ice sheet expansion and cooling and affect regional precipitation, we infer that long-period astronomical climate forcing is a major determinant of species turnover in small mammals and probably other groups as well.

  8. Factors influencing turnover intention among registered nurses in Samar Philippines.

    Science.gov (United States)

    Labrague, Leodoro J; Gloe, Donna; McEnroe, Denise M; Konstantinos, Kostas; Colet, Paolo

    2018-02-01

    Despite the massive nurse migration and turnover of nurses in the Philippines, there remains a lack of studies describing factors influencing the migration of Filipino nurses. This study explored the effects of nurses' characteristics, work satisfaction, and work stress with the intent to leave an organization among registered nurses in the Philippines. This study utilized a descriptive, cross-sectional approach. One hundred sixty six (166) nurses participated in the study during the months of September 2015 to December 2015. Three standardized instruments were used in the study: Job Satisfaction Index (JSI), Job Stress Scale (JSS), and Turnover Intention Inventory Scale (TIIS). Data were analyzed using descriptive and inferential statistical tools. Nurses' ages were found to significantly influence their turnover intentions. Job satisfaction (β=-0.47, p=0.001) and job stress (β=0.23, p=0.001) strongly predicted turnover intentions in the nurses. The mean values for the job satisfaction scale, job stress scale, and turnover intention inventory scale were 3.13 (SD=0.60), 2.74 (SD=0.71), and 2.43 (SD=0.67) respectively. Several predictors of turnover intentions were determined in this study through nurses' age, job satisfaction, and job stress as being the most influential factors. Efforts to increase nurses' job satisfaction and reduce job stress should be implemented to halt further loss of these skilled groups of healthcare professionals. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Stable isotopic constraints on global soil organic carbon turnover

    Science.gov (United States)

    Wang, Chao; Houlton, Benjamin Z.; Liu, Dongwei; Hou, Jianfeng; Cheng, Weixin; Bai, Edith

    2018-02-01

    Carbon dioxide release during soil organic carbon (SOC) turnover is a pivotal component of atmospheric CO2 concentrations and global climate change. However, reliably measuring SOC turnover rates on large spatial and temporal scales remains challenging. Here we use a natural carbon isotope approach, defined as beta (β), which was quantified from the δ13C of vegetation and soil reported in the literature (176 separate soil profiles), to examine large-scale controls of climate, soil physical properties and nutrients over patterns of SOC turnover across terrestrial biomes worldwide. We report a significant relationship between β and calculated soil C turnover rates (k), which were estimated by dividing soil heterotrophic respiration rates by SOC pools. ln( - β) exhibits a significant linear relationship with mean annual temperature, but a more complex polynomial relationship with mean annual precipitation, implying strong-feedbacks of SOC turnover to climate changes. Soil nitrogen (N) and clay content correlate strongly and positively with ln( - β), revealing the additional influence of nutrients and physical soil properties on SOC decomposition rates. Furthermore, a strong (R2 = 0.76; p global models of soil C turnover and thereby improving predictions of multiple global change influences over terrestrial C-climate feedback.

  10. Pengaruh Leadership Capability Terhadap Turnover Intention Melalui Job Satisfaction Di PT. Rajawali Nusindo

    OpenAIRE

    Kevin, Brillian

    2017-01-01

    Employee turnover mengarah pada Kenyataan akhir yang dihadapi Perusahaan (kehilangan sejumlah karyawan) pada periode tertentu, sedangkan keinginan pindah kerja (turnover intentions) sendiri mengacu kepada hasil evaluasi individu mengenai kelanjutan hubungannya dengan sebuah Perusahaan yang belum diwujudkan dalam tindakan nyata meninggalkan Perusahaan tersebut.Bagi PT Rajawali Nusindo, turnover intention juga menjadi salah satu masalah yang dihadapi oleh Perusahaan dikarenakan turnover yang te...

  11. Cell-cycle calcium transients driven by cyclic changes in inositol trisphosphate levels.

    Science.gov (United States)

    Ciapa, B; Pesando, D; Wilding, M; Whitaker, M

    1994-04-28

    Transient changes in intracellular calcium ([Ca2+]i) have been shown to punctuate the cell cycle in various types of cells in culture and in early embryos. The [Ca2+]i transients are correlated with cell-cycle events: pronuclear migration, nuclear envelope breakdown, the metaphase-anaphase transition of mitosis, and cytokinesis. Mitotic events can be induced by injecting calcium and prevented by injecting calcium chelators into the sea urchin embryo. Cell-cycle calcium transients differ from the transients linked to membrane signal transduction pathways: they are generated by an endogenous mechanism, not by plasma membrane receptor complexes, and their trigger is unknown. We report here that the phosphoinositide messenger system oscillates during the early embryonic cell cycle in the sea urchin, leading to cyclic increases in inositol trisphosphate that trigger cell-cycle [Ca2+]i transients and mitosis by calcium release from intracellular stores.

  12. Nutrients and neurodevelopment: lipids.

    Science.gov (United States)

    González, Horacio F; Visentin, Silvana

    2016-10-01

    Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding. Sociedad Argentina de Pediatría.

  13. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  14. Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia.

    Directory of Open Access Journals (Sweden)

    Fernando D Villarreal

    Full Text Available Myo-inositol (Ins is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus. Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS and inositol monophosphatase (IMPase, by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1 were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P, mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress.

  15. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Vittorio Unfer1,

    2017-10-01

    Full Text Available Myo-inositol (MI supplementation in women with polycystic ovary syndrome (PCOS has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016. Only randomized controlled trials (RCTs investigating the effects of MI alone or combined with DdCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = −1.021 μU/mL, 95% CI: −1.791 to −0.251, P = 0.009 and homeostasis model assessment (HOMA index (SMD = −0.585, 95% CI: −1.145 to −0.025, P = 0.041 were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = −0.49, 95% CI: −1.072 to 0.092, P = 0.099, whereas androstenedione levels remained unaffected. Throughout a subgroup’s meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050–0.801, P = 0.026. These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

  16. Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia.

    Science.gov (United States)

    Villarreal, Fernando D; Kültz, Dietmar

    2015-01-01

    Myo-inositol (Ins) is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus). Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS) and inositol monophosphatase (IMPase), by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1) were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P), mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P) is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress.

  17. Myo-inositol based nano-PCM for solar thermal energy storage

    International Nuclear Information System (INIS)

    Singh, D.K.; Suresh, S.; Singh, H.; Rose, B.A.J.; Tassou, S.; Anantharaman, N.

    2017-01-01

    Highlights: • Properties of Myo-Inositol laden with Al 2 O 3 and CuO nanoparticles was studied. • The melting point was found to increase for MI-A and decrease for MI-C. • MI interacted only physically on addition of NPs. • Mass changes were <3% after thermal cycling of MI-A and MI-C. • MI-A is more suited for thermal energy storage than MI-C. - Abstract: The thermo-physical behavior of Myo-Inositol (MI), (a sugar alcohol), was investigated as a potential material for developing more compact solar thermal energy storage systems than those currently available. This latent heat storage medium could be utilized for commercial and industrial applications using solar thermal energy storage in the temperature range of 160–260 °C, if its thermal performance was modified. The objective of this investigation was to determine via experimentation, if Al 2 O 3 and CuO nanoparticles dispersed in pure MI for mixtures of 1, 2 and 3% (by weight) improved the thermal performance of MI for solar thermal energy systems. Nanoparticles only physically interacted with MI, and not chemically, even after 50 thermal cycles. The distribution of CuO nanoparticles in the nano-PCM was found to be more uniform than alumina nanoparticles. After cycling, nano-MIs studied here suffered a lower decrease in heat of fusion than pure MI, which makes nano-MIs more suitable for solar thermal storage applications at 160–260 °C. Between CuO and Al 2 O 3 nanoparticles, latter was found to be more suitable for compact solar thermal energy storage owing to an increase in melting point observed.

  18. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...... of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations...

  19. Using Job Embeddedness Factors to Explain Voluntary Turnover in Five European Countries

    OpenAIRE

    Tanova, Cem

    2006-01-01

    This paper investigates actual voluntary turnover from the employee's perspective using a large European dataset integrating the available job factors related to job embeddedness and other variables that have been related to turnover in previous turnover models. The study shows that the traditional turnover model, where ease of movement and desire of movement are regarded as important predictors of turnover, receives support. However, the study also shows the job embeddedness factors play a k...

  20. Bone turnover marker reference intervals in young females.

    Science.gov (United States)

    Callegari, Emma T; Gorelik, Alexandra; Garland, Suzanne M; Chiang, Cherie Y; Wark, John D

    2017-07-01

    Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131  µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.

  1. Role of inositol (1,4,5)trisphosphate in epidermal growth factor-induced Ca2+ signaling in A431 cells

    DEFF Research Database (Denmark)

    Hughes, A R; Bird, G S; Obie, J F

    1991-01-01

    to thapsigargin. In nominally Ca(2+)-free medium, the addition of bradykinin to A431 cells rapidly but transiently increased inositol 1,4,5-trisphosphate and, in parallel fashion, transiently increased cytosolic Ca2+. Unexpectedly, under these experimental conditions, epidermal growth factor elicited a small...... but significant Ca2+ signal after the addition of bradykinin. Experiments were designed to determine whether the Ca2+ response to epidermal growth factor after bradykinin results from mobilization of Ca2+ by an inositol 1,4,5-trisphosphate-independent mechanism. Epidermal growth factor stimulated additional...... inositol 1,4,5-trisphosphate formation in bradykinin-treated cells. Furthermore, the Ca2+ signals elicited by both bradykinin and epidermal growth factor were blocked in cells microinjected with the inositol 1,4,5-trisphosphate receptor antagonist heparin, whereas the intracellular Ca(2+)-ATPase inhibitor...

  2. Mn++-stimulated 3H-inositol incorporation in cultured vascular smooth muscle cells: deficiency in cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Buck, S.H.; Nabika, T.; Lovenberg, W.

    1985-01-01

    Incubation of cultured dissociated aortic smooth muscle cells from Wistar-Kyoto rats (WKY) with Mn++ resulted in a 10-fold stimulation of 3 H-myo-inositol incorporation into membrane phospholipids. The stimulation was temperature and energy dependent. The Mn++ EC50 was 1 mM and maximum stimulation occurred at 10 mM Mn++. Other cations were ineffective. In cells from spontaneously hypertensive rats (SHR), the Mn++ EC50 was unchanged whereas the maximum stimulation of 3 H-inositol incorporation was reduced by 50% compared to cells from parallel WKY cultures. These results suggest that in SHR cultured vascular smooth muscle cells there is a deficiency in an enzymatic process mediating exchange of free inositol with the headgroup inositol of membrane phosphatidylinositol

  3. Arabidopsis FHY3 and FAR1 Regulate Light-Induced myo-Inositol Biosynthesis and Oxidative Stress Responses by Transcriptional Activation of MIPS1.

    Science.gov (United States)

    Ma, Lin; Tian, Tian; Lin, Rongcheng; Deng, Xing-Wang; Wang, Haiyang; Li, Gang

    2016-04-04

    myo-Inositol-1-phosphate synthase (MIPS) catalyzes the limiting step of inositol biosynthesis and has crucial roles in plant growth and development. In response to stress, the transcription of MIPS1 is induced and the biosynthesis of inositol or inositol derivatives is promoted by unknown mechanisms. Here, we found that the light signaling protein FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1) regulate light-induced inositol biosynthesis and oxidative stress responses by activating the transcription of MIPS1. Disruption of FHY3 and FAR1 caused light-induced cell death after dark-light transition, precocious leaf senescence, and increased sensitivity to oxidative stress. Reduction of salicylic acid (SA) accumulation by overexpression of SALICYLIC ACID 3-HYDROXYLASE largely suppressed the cell death phenotype of fhy3 far1 mutant plants, suggesting that FHY3- and FAR1-mediated cell death is dependent on SA. Furthermore, comparative analysis of chromatin immunoprecipitation sequencing and microarray results revealed that FHY3 and FAR1 directly target both MIPS1 and MIPS2. The fhy3 far1 mutant plants showed severely decreased MIPS1/2 transcript levels and reduced inositol levels. Conversely, constitutive expression of MIPS1 partially rescued the inositol contents, caused reduced transcript levels of SA-biosynthesis genes, and prevented oxidative stress in fhy3 far1. Taken together, our results indicate that the light signaling proteins FHY3 and FAR1 directly bind the promoter of MIPS1 to activate its expression and thereby promote inositol biosynthesis to prevent light-induced oxidative stress and SA-dependent cell death. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  4. The effect of fertilization levels and genetic deployment on soil organic matter chemistry and turnover in managed loblolly pine forests

    Science.gov (United States)

    Vogel, J. G.; Jokela, E. J.; He, D.; Hockaday, W. C.; Schuur, E. A.

    2013-12-01

    Soil organic matter (SOM) dynamics were examined for two managed loblolly pine forests (Pinus taeda L.) located in north-central Florida on sandy Spodosols. The study designs were split-plots with the whole plots designated as fertilization levels, and the split-plots full-sib families of loblolly pine. The forests were aged 9 and 10 years at sampling. Roots, wood, and charcoal were hand-picked from SOM and density fractionation (1.6 g/ml) used to further separate SOM into a light (LF) and heavy fraction (HF). LF turnover rates were estimated using radiocarbon and LF chemistry determined with nuclear magnetic resonance (NMR). Family or fertilization level effects on the mass of SOM components were not significant at both sites. The largest proportions of SOM were in the LF (83% and 85%) and wood (6% and 9%). Varying in relative contributions were charcoal (2% and 3%) and the HF (4% and 1%) while fine dead roots were between 1-2% of total SOM. Higher fertilization levels generally depressed fine root (family and soil horizon. The turnover rate for one family under low fertilization was significantly slower (14 yrs) than the other treatments. This treatment also had a greater proportion of lignin, and given the slow turnover, the results suggest this lignin derived from the previous stand. At the other site lignin and lipids differed significantly (pfamilies. These results suggest that tree genetics in forests can influence SOM chemistry, but that family and the degree of fertilization have little net effect on SOM chemistry and turnover.

  5. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation, and the com......Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  6. Developing human capital: what is the impact on nurse turnover?

    Science.gov (United States)

    Rondeau, Kent V; Williams, Eric S; Wagar, Terry H

    2009-09-01

    To investigate the impact that increasing human capital through staff training makes on the voluntary turnover of registered nurses. Healthcare organizations in Canada, the United Kingdom, the United States, and Australia are experiencing turbulent nursing labour markets characterized by extreme staff shortages and high levels of turnover. Organizations that invest in the development of their nursing human resources may be able to mitigate high turnover through the creation of conditions that more effectively develop and utilize their existing human capital. A questionnaire was sent to the chief nursing officers of 2208 hospitals and long-term care facilities in every province and territory of Canada yielding a response rate of 32.3%. The analysis featured a three-step hierarchical regression with two sets of control variables. After controlling for establishment demographics and local labour market conditions, perceptions of nursing human capital and the level of staff training provided were modestly associated with lower levels of establishment turnover. and implications for Nursing Management The results suggest that healthcare organizations that have made greater investments in their nursing human capital are more likely to demonstrate lower levels of turnover of their registered nursing personnel.

  7. Alterations in RNA turnover following x-irradiation

    International Nuclear Information System (INIS)

    Hetzel, F.W.; Kolodny, G.M.

    1975-01-01

    Mouse embryonic fibroblasts, 3T3, were irradiated in growing and confluent states with 280KV x-rays to a dose of 3750 rads. All cells were prelabeled while growing with 14 C thymidine for 24 hours and for 24 hours with 3 H uridine in either the growing or confluent state. The turnover of prelabeled cellular RNA was then studied. While RNA turnover normally occurs in confluent cells and does not occur in subconfluent cells the results of this study suggested the existence of RNA turnover in both cell populations following radiation. The rate of RNA turnover in irradiated confluent cells was less than that seen in normal confluent cells while for irradiated growing cells the rate of turnover was higher than in controls. The two rates were approximately equal in both irradiated populations. In each case the amount of prelabeled DNA lost from the acid insoluble fraction was approximately 50 percent after 10 days. The possible significance of these results in relation to radiation induced giant cell formation and alterations in RNA minor bases will be discussed

  8. Investigation on the turnover of plant proteins. 2

    International Nuclear Information System (INIS)

    Becker, R.; Winkler, E.; Jung, K.; Huebner, G.

    1981-01-01

    Based on kinetic analyses of amino acid and protein turnover by means of compartment models the synthesis and degradation of the soluble proteins in etiolated epicotyl segments of Pisum sativum L. as well as their dependence on the herbicide 2'-methyl-4'-chlorophenoxyacetic acid (MCPA) were determined quantitatively. The segments were incubated for 10 h in a medium containing 14 C-leucine and subsequently placed in an inactive medium. The radioactivity in the soluble proteins and in the amino acid fraction was followed up for a total of 24 h. A 3-pool model in which the total measurable amino acid pool was divided into a direct precursor pool for protein synthesis and into a degradation pool was best suited to interpret the data. The turnover rate for the soluble proteins of untreated epicotyl segments was determined to be 0.058 h -1 ; at an MCPA concentration of 10 -4 M this value was nearly doubled. An increased proteolytic activity in the epicotyl segments ran parallel to the change of the turnover rate in dependence on MCPA concentration. The heterogeneity of the soluble protein with respect to the turnover rate was investigated by means of 3 H/ 14 C double labelling for individual protein fractions separated by gel electrophoresis. The results obtained in this way were comparable with those of the total pool turnover. (author)

  9. Hepatic metallothionein turnover in toxic milk mutant mice

    International Nuclear Information System (INIS)

    Rauch, H.; Wells, A.J.

    1989-01-01

    Homozygous toxic milk (tx tx) mice are characterized by extraordinary hepatic copper levels, the excess copper being associated with metallothionein (MT). We have compared MT metabolism in normal and mutant animals. To evaluate MT turnover, animals were injected with 35 S-cysteine, followed in 24 hours by a cold cysteine chase. Animals were sacrificed daily and radioactivity in hepatic MT fractions was used to calculated MT half-life. Based on uptake of label, MT synthesis is very active in tx mice, this MT having a half life of 4-5 days. MT synthesis in normals is much lower, one fourth or less radioactivity. To increase MT synthesis, normals were primed by prior zinc (150 μg) or copper (90 μg) injection; MT label was doubled, the resulting MT showing a slow turnover rate, half-life about 6 days. Another group of normals were primed as above but with metal injections repeated daily so as to measure turnover under conditions of continuous high level MT synthesis, comparable to those prevailing in mutant animals. Although initial label uptake was the same as that of previously primed animals, turnover was hastened, half-life 2-3 days. Thus, copper accumulation in mutants is attributable at least in part to increased rate of synthesis coupled with decreased rate of turnover of MT

  10. Move over! Stock turnover, retrofit and industrial energy efficiency

    International Nuclear Information System (INIS)

    Worrell, Ernst; Biermans, Gijs

    2005-01-01

    We demonstrate the importance of stock turnover on industrial energy efficiency through a literature review and a case study of energy-intensive equipment, i.e. the electric arc furnace in the US steel industry. We describe the common methods for assessing stock turnover. We have found that both stock turnover and retrofit are important elements to explain the energy efficiency improvement rates. We investigated the development of electricity use in electric arc furnaces in the United States by tracking the development of individual furnaces over the period 1990-2002. This provides a detailed picture of changes in the stock or fleet of furnaces through turnover and/or retrofit. Our results confirm the results of other empirical studies that there is no clear lifetime of equipment. However, retired furnaces are distinctly less efficient than furnaces remaining in the stock, while new furnaces are distinctly more efficient than the average stock. We found an annual average improvement in specific electricity consumption of 1.3%/year over the studied period, of which 0.7%/year was due to stock turnover and 0.5%/year due to retrofit of stock in service throughout the period

  11. Turnover of recently assimilated carbon in arctic bryophytes.

    Science.gov (United States)

    Street, L E; Subke, J A; Sommerkorn, M; Heinemeyer, A; Williams, M

    2011-10-01

    Carbon (C) allocation and turnover in arctic bryophytes is largely unknown, but their response to climatic change has potentially significant impacts on arctic ecosystem C budgets. Using a combination of pulse-chase experiments and a newly developed model of C turnover in bryophytes, we show significant differences in C turnover between two contrasting arctic moss species (Polytrichum piliferum and Sphagnum fuscum). (13)C abundance in moss tissues (measured up to 1 year) and respired CO(2) (traced over 5 days) were used to parameterise the bryophyte C model with four pools representing labile and structural C in photosynthetic and stem tissue. The model was optimised using an Ensemble Kalman Filter to ensure a focus on estimating the confidence intervals (CI) on model parameters and outputs. The ratio of aboveground NPP:GPP in Polytrichum piliferum was 23% (CI 9-35%), with an average turnover time of 1.7 days (CI 1.1-2.5 days). The aboveground NPP:GPP ratio in Sphagnum fuscum was 43% (CI 19-65%) with an average turnover time of 3.1 days (CI 1.6-6.1 days). These results are the first to show differences in C partitioning between arctic bryophyte species in situ and highlight the importance of modelling C dynamics of this group separately from vascular plants for a realistic representation of vegetation in arctic C models.

  12. [A model on turnover intention of chief nurse officers].

    Science.gov (United States)

    Park, Kwang-Ok; Kim, Jong Kyung; Kim, Se Young; Chang, Sunju

    2012-02-01

    The purpose of this study was to test the turnover intention model for chief nurse officers in general hospitals. The variables for the study included job stress, social support, job satisfaction, and organization commitment. A predictive, non-experimental design was used with a sample of 144 chief nurse officers from 144 general hospitals. Data were collected using self-administered questionnaires and analyzed using SPSS, AMOS program. The overall fitness of the hypothetical model to the data was good (χ²=16.80, p=.052, GFI=.96, AGFI=.90, NFI=.97, CFI=.99). Job stress, social support, job satisfaction, and organization commitment explained 59.0% of the variance in turnover intention by chief nurse officers. Both organization commitment and social support directly influenced turnover intention for chief nurse officers, and job stress and job satisfaction indirectly influenced turnover intention. The results imply that chief nurse officers in hospitals need social support and management of job stress to increase job satisfaction and organization commitment, and lower turnover intention.

  13. Investigating the adequacy of the Competence-Turnover Intention Model: how does nursing competence affect nurses' turnover intention?

    Science.gov (United States)

    Takase, Miyuki; Teraoka, Sachiko; Kousuke, Yabase

    2015-03-01

    The aim of this study was to test the adequacy of the Competence-Turnover Intention Model, which was developed to identify how nursing competence could affect nurses' turnover intention (nurses' intention to voluntarily leave an organisation). Recent studies have suggested that the level of nursing competence is negatively related to nurses' intention to leave their jobs, suggesting that a lack of competence threatens both the quality and quantity of the nursing workforce. However, the mechanism of how nursing competence affects nurses' turnover intention has not been explored previously. A cross-sectional survey design was used. Surveys were distributed to 1337 Japanese registered nurses/midwives in October, 2013. The adequacy of the model was analysed using structural equation modelling. In total, 766 questionnaires were returned, with a return rate of 57%. The model fitted well with the data. The results showed that the level of nursing competence was related positively to the quantity of organisational rewards they felt they had received, and negatively related to the level of exhaustion they experienced. Moreover, the perceived organisational rewards and exhaustion were correlated with nurses' turnover intention through affective commitment. The Competence-Turnover Intention Model is useful for explaining how nursing competence impacts on their turnover intention. Clinical implications derived from the findings are that: promoting nursing competence is key to improving not only the quality of care provided by nurses, but also to retaining the nursing workforce, and the model can be used to develop strategies that would mitigate their turnover intention. © 2014 John Wiley & Sons Ltd.

  14. α-thrombin-induced inositol phosphate formation in G0-arrested and cycling hamster lung fibroblasts: evidence for a protein kinase C-mediated desensitization response

    International Nuclear Information System (INIS)

    L'allemain, G.; Paris, S.; Magnaldo, I.; Pouyssegur, J.

    1986-01-01

    In resting Chinese hamster fibroblasts (CCL39) α-thrombin rapidly induces the breakdown of phosphoinositides. Accumulation of inositol phosphates (IP), measured in the presence of Li + , is detectable within 5s (seconds) of thrombin stimulation. Formation of inositol tris- and bisphosphates slightly precedes that of inositol monophosphate, indicating that thrombin activates primarily the phospholipase C-mediated generation of inositol trisphosphate from phosphatidylinositol 4,5-bisphosphate. Initial rates of IP production increase with thrombin concentration, with no apparent saturability over the range 10 -4 -10 U/ml. Thrombin-induced phosphoinositide hydrolysis rapidly desensitizes (t/sub 1/2/ > 5 min), but a residual activity, corresponding to about 10% of the initial stimulation is sustained for at least 9 h, in contrast with the undetectable activity of G0-arrested cells. This apparent desensitization may be due to a feedback regulation by protein kinase C, since pretreatment with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) markedly inhibits (by up to 70%) subsequent thrombin-induced inositol phosphate formation. This up regulation was found maximal in A51, a very well growth-arrested CCL39 derivative,and reduced or virtually abolished in two tumoral and growth factor-relaxed derivatives of CCL39. Although preliminary, this observation suggests that a persistent activation of phosphatidyl inositol breakdown might operate in variants selected for autonomous growth

  15. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance.

    Science.gov (United States)

    Kamenov, Zdravko; Kolarov, Georgi; Gateva, Antoaneta; Carlomagno, Gianfranco; Genazzani, Alessandro D

    2015-02-01

    Insulin resistance plays a key role in the pathogenesis of polycystic ovarian syndrome (PCOS). One of the methods for correcting insulin resistance is using myo-inositol. The aim of the present study is to evaluate the effectiveness of myo-inositol alone or in combination with clomiphene citrate for (1) induction of ovulation and (2) pregnancy rate in anovulatory women with PCOS and proven insulin resistance. This study included 50 anovulatory PCOS patients with insulin resistance. All of them received myo-inositolduring three spontaneous cycles. If patients remained anovulatory and/or no pregnancy was achieved, combination of myo-inositol and clomiphene citrate was used in the next three cycles. Ovulation and pregnancy rate, changes in body mass index (BMI) and homeostatic model assessment (HOMA) index and the rate of adverse events were assessed. After myo-inositol treatment, ovulation was present in 29 women (61.7%) and 18 (38.3%) were resistant. Of the ovulatory women, 11 became pregnant (37.9%). Of the 18 myo-inositol resistant patients after clomiphene treatment, 13 (72.2%) ovulated. Of the 13 ovulatory women, 6 (42.6%) became pregnant. During follow-up, a reduction of body mass index and HOMA index was also observed. Myo-inositol treatment ameliorates insulin resistance and body weight, and improves ovarian activity in PCOS patients.

  16. Fermentation of phytic acid from lamtoro gung seeds (Leucaena leucocephala to produce inositol and tannin as pharmaceutical commodity

    Directory of Open Access Journals (Sweden)

    I. A.R. Bakti

    2003-12-01

    Full Text Available The research was done to define the effect of tempe yeast concentration on inositol and tannin contents of fermented lamtoro gung seeds (Leucaena leucocephala. This is a research with completely randomized design using four doses of tempe yeast, i.e. 0 %, 5 %, 10 %, and 15 %. Each treatment was replicated 4 times. The resulted data were analyzed by analysis of variance and the significant differences were tested by least significantly difference test. Tannin was analyzed by Lowenthal-Procter method. The result of the research showed that the treatment had significant effects (P<0.05 on the parameter measured. The highest inositol with lowest tannin contents were found by using 15 % tempe yeast and duration of fermentation 96 hours, that is 0.2631 %. (Med J Indones 2003; 12: 236-42Keywords: tempe yeast

  17. Changes of Protein Turnover in Aging Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Dhondt, Ineke; Petyuk, Vladislav A.; Bauer, Sophie; Brewer, Heather M.; Smith, Richard D.; Depuydt, Geert; Braeckman, Bart P.

    2017-07-05

    Protein turnover rates severely decline in aging organisms, including C. elegans. However, limited information is available on turnover dynamics at the individual protein level during aging. We followed changes in protein turnover at one-day resolution using a multiple-pulse 15Nlabeling and accurate mass spectrometry approach. Forty percent of the proteome shows gradual slowdown in turnover with age, whereas only few proteins show increased turnover. Decrease in protein turnover was consistent for only a minority of functionally related protein subsets, including tubulins and vitellogenins, whereas randomly diverging turnover patterns with age were the norm. Our data suggests increased heterogeneity of protein turnover of the translation machinery, whereas protein turnover of ubiquitin-proteasome and antioxidant systems are well-preserved over time. Hence, we presume that maintenance of quality control mechanisms is a protective strategy in aging worms, although the ultimate proteome collapse is inescapable.

  18. L-myo-inosose-1 as a probable intermediate in the reaction catalyzed by myo-inositol oxygenase

    International Nuclear Information System (INIS)

    Naber, N.I.; Swan, J.S.; Hamilton, G.A.

    1986-01-01

    In previous investigations, it was necessary to have Fe(II) and cysteine present in order to assay the catalytic activity of purified hog kidney myo-inositol oxygenase. In the present study it was found that, if this purified nonheme iron enzyme is slowly frozen in solution with glutathione and stored at -20 degrees C, it is fully active in the absence of activators if catalase is present to remove adventitious H 2 O 2 . With this simpler assay system it was possible to clarify the effects of several variables on the enzymic reaction. Thus, the maximum velocity is pH-dependent with a maximum around pH 9.5, but the apparent Km for myo-inositol (air atmosphere) remains constant at 5.0 mM throughout a broad pH range. The enzyme is quite specific for its substrate myo-inositol, is very sensitive to oxidants and reductants, but is not affected by a variety of complexing agents, nucleotides, sulfhydryl reagents, etc. In other experiments it was found that L-myo-inosose-1, a potential intermediate in the enzymic reaction, is a potent competitive inhibitor (Ki = 62 microM), while other inososes and a solution thought to contain D-glucodialdehyde, another potential intermediate, are weak inhibitors. Also, both a kinetic deuterium isotope effect (kH/kD = 2.1) and a tritium isotope effect (kH/kT = 7.5) are observed for the enzymic reaction when [1-2H]- and [1-3H]-myo-inositol are used as reactants. These latter results are considered strong evidence that the oxygenase reaction proceeds by a pathway involving L-myo-inosose-1 as an intermediate rather than by an alternative pathway that would have D-glucodialdehyde as the intermediate

  19. Thermococcus kodakarensis Mutants Deficient in Di-myo-Inositol Phosphate Use Aspartate To Cope with Heat Stress▿§

    Science.gov (United States)

    Borges, Nuno; Matsumi, Rie; Imanaka, Tadayuki; Atomi, Haruyuki; Santos, Helena

    2010-01-01

    Many of the marine microorganisms which are adapted to grow at temperatures above 80°C accumulate di-myo-inositol phosphate (DIP) in response to heat stress. This led to the hypothesis that the solute plays a role in thermoprotection, but there is a lack of definitive experimental evidence. Mutant strains of Thermococcus kodakarensis (formerly Thermococcus kodakaraensis), manipulated in their ability to synthesize DIP, were constructed and used to investigate the involvement of DIP in thermoadaptation of this archaeon. The solute pool of the parental strain comprised DIP, aspartate, and α-glutamate. Under heat stress the level of DIP increased 20-fold compared to optimal conditions, whereas the pool of aspartate increased 4.3-fold in response to osmotic stress. Deleting the gene encoding the key enzyme in DIP synthesis, CTP:inositol-1-phosphate cytidylyltransferase/CDP-inositol:inositol-1-phosphate transferase, abolished DIP synthesis. Conversely, overexpression of the same gene resulted in a mutant with restored ability to synthesize DIP. Despite the absence of DIP in the deletion mutant, this strain exhibited growth parameters similar to those of the parental strain, both at optimal (85°C) and supraoptimal (93.7°C) temperatures for growth. Analysis of the respective solute pools showed that DIP was replaced by aspartate. We conclude that DIP is part of the strategy used by T. kodakarensis to cope with heat stress, and aspartate can be used as an alternative solute of similar efficacy. This is the first study using mutants to demonstrate the involvement of compatible solutes in the thermoadaptation of (hyper)thermophilic organisms. PMID:19880594

  20. ADP stimulation of inositol phosphates in hepatocytes: role of conversion to ATP and stimulation of P2Y2 receptors.

    Science.gov (United States)

    Dixon, C Jane; Hall, John F; Boarder, Michael R

    2003-01-01

    1 Accumulation of inositol (poly)phosphates (InsP(x)) has been studied in rat hepatocytes labelled with [(3)H]inositol. Stimulation with ADP resulted in a significant increase in total [(3)H]InsP(x), whereas 2-MeSADP had only a small effect and ADPbetaS was ineffective. UTP and ITP also stimulated substantial increases in [(3)H]InsP(x). 2 The dose-response curve to ADP was largely unaltered by the presence of the P2Y(1) antagonist, adenosine-3'-phosphate-5'-phosphate (A3P5P). Similarly, inclusion of MRS 2179, a more selective P2Y(1) antagonist, had no effect on the dose-response curve to ADP. 3 The inclusion of hexokinase in the assay reduced, but did not abolish, the response to ADP. 4 HPLC analysis revealed that ADP in the medium was rapidly converted to AMP and ATP. The inclusion of hexokinase removed ATP, but exacerbated the decline in ADP concentration, leading to increased levels of AMP. 2-MeSADP was stable in the medium and ATP was largely unaffected. 5 The addition of the adenylate kinase inhibitor, diadenosine pentaphosphate (Ap(5)A) significantly reduced the ADP response. HPLC analysis conducted in parallel demonstrated that this treatment inhibited conversion of ADP to ATP and AMP. 6 Inclusion of the P1 antagonist CGS 15943 had no effect on the dose-response curve to ADP. 7 These observations indicate that hepatocytes respond to ADP with an increase in inositol (poly)phosphates following conversion to ATP. P2Y(1) activation in hepatocytes does not appear to be coupled to inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) production.

  1. Leukotriene B4 (LTB4) induces formation of inositol-phosphates (IP's) in rat peritoneal polymorphonuclear leukocytes (PMN's)

    International Nuclear Information System (INIS)

    Chi-Rosso, G.; Crooke, S.T.; Mong, S.

    1986-01-01

    LTB 4 induced rapid breakdown of prelabeled inositol-phospholipids (PI) in rat PMN. Formation of [ 3 H]-inositol-trisphosphate ([ 3 H]-IP 3 ) was rapid, with a peak of 250-300% of the control level, after 5-15 sec of stimulation with LTB 4 . Accumulation of [ 3 H]-inositol-bisphosphate ([ 3 H]-IP 2 ) was rapid, peaking after 30 sec of stimulation. [ 3 H]-inositol-monophosphate ([ 3 H]-IP 1 ) accumulated gradually in the presence of LiCl. The kinetics of [ 3 H]-IP 3 , [ 3 H]-IP 2 and [ 3 H]-IP 1 accumulation suggested that LTB 4 may interact with receptors in PMNs, activate phospholipase C which, in turn, induces hydrolysis of PI. The agonist activities of several LTB 4 analogs were employed to investigate the structure activity relationship of LTB 4 receptor mediated activation of PI hydrolysis. Increases in [ 3 H]-IP 3 formation were dependent upon the concentration of LTB 4 and the agonist analogs. The rank order potency of these analogs were equivalent to that of the pharmacological activity of LTB 4 agonists in the chemotaxis assay. Furthermore, the Islet activation protein (IAP) inhibited LTB 4 induced [ 3 H]-IP 3 formation. The tumor promoting phorbomyristate ester also inhibited LTB 4 induced [ 3 H]-IP 3 formation. These results suggest LTB 4 may interact with receptors in rat PMNs, activate G/sub i/ protein regulated phospholipase C and induce [ 3 H]-IP 3 formation

  2. Seawater acclimation and inositol monophosphatase isoform expression in the European eel (Anguilla anguilla) and Nile tilapia (Orechromis niloticus).

    Science.gov (United States)

    Kalujnaia, Svetlana; Gellatly, Steven A; Hazon, Neil; Villasenor, Alfredo; Yancey, Paul H; Cramb, Gordon

    2013-08-15

    Inositol monophosphatase (IMPA) is responsible for the synthesis of inositol, a polyol that can function as an intracellular osmolyte helping re-establish cell volume when exposed to hypertonic environments. Some epithelial tissues in euryhaline teleosts such as the eel and tilapia encounter considerable hyperosmotic challenge when fish move from freshwater (FW) to seawater (SW) environments; however, the roles played by organic osmolytes, such as inositol, have yet to be determined. Syntenic analysis has indicated that, as a result of whole genome- and tandem-duplication events, up to six IMPA isoforms can exist within teleost genomes. Four isoforms are homologs of the mammalian IMPA1 gene, and two isoforms are homologs of the mammalian IMPA2 gene. Although the tissue-dependent isoform expression profiles of the teleost isoforms appear to be species-specific, it was primarily mRNA for the IMPA1.1 isoform that was upregulated in epithelial tissues after fish were transferred to SW (up to 16-fold in eel and 90-fold in tilapia). Although up-regulation of IMPA1.1 expression was evident in many tissues in the eel, more substantial increases in IMPA1.1 expression were found in tilapia tissues, where SW acclimation resulted in up to 2,000-fold increases in protein expression, 16-fold increases in enzyme activity and 15-fold increases in tissue inositol contents. Immunohistochemical studies indicated that the tissue and cellular distribution of IMPA1.1 protein differed slightly between eels and tilapia; however, in both species the basal epithelial cell layers within the skin and fin, and the branchial epithelium and interstitial cells within the kidney, exhibited high levels of IMPA1.1 protein expression.

  3. Stereospecific recognition sites for [3H]inositol(1,4,5)-triphosphate in particulate preparations of rat cerebellum

    International Nuclear Information System (INIS)

    Willcocks, A.L.; Cooke, A.M.; Potter, B.V.; Nahorski, S.R.

    1987-01-01

    A very high density of stereospecific binding sites for inositol-(1,4,5)P3 have been identified in rat cerebellar membranes using [ 3 H]inositol-(1,4,5)P3 and a rapid centrifugation step to separate free and bound ligand. Binding was shown to be rapid and reversible and of relatively high affinity (KD 23 nM). Incubations were carried out at 4 degrees and under these conditions HPLC analysis demonstrated that there was no significant metabolism of [ 3 H]-(1,4,5)P3 in the presence or absence of ATP over 15 min. The specificity of the site has been carefully evaluated using both natural and novel synthetic inositol phosphates. The stereospecificity is very marked with the D-, DL- and L-isomers of Ins(1,4,5)P3 showing a 1:4:2000 ratio of affinity for the binding site. D-Ins(2,4,5)P3 was the only other phosphate to show relatively high affinity (KD 1500 nM). HPLC-pure Ins(1,3,4)P3 and Ins(1,3,4,5)P4 were substantially weaker and Ins(1,4)P2, Ins-2-P1, Ins-1-P1, Ins(1,2)-cyclic P1 and inositol were totally inactive at concentrations less than 50 microM. These data are discussed in relation to a putative receptor on the endoplasmic reticulum by which Ins(1,4,5)P3 can initiate the release of bound Ca 2+

  4. PENGARUH JOB SATISFACTION TERHADAP OCB DAN TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Febru Rida Ningsih

    2015-06-01

    Full Text Available This article aims to provide the impact of job satisfaction to OCB and turnover intention. This study used a quantitative method with a statistical analysis. Simple analysis regression used to test each hypotheses. The object of this research is a branch of national bank. Population in this research are entire employees of a brach of national bank that is e non frontliner employees. Non-probability sampling is used of this reseach. The measurement of job satiafaction and turnover intention variables used likert scale that developed by Rinaldi (2008 and measurement of OCB variable adopted from  Organ (1988.  The result of this research has shown that hypotheses one is rejected and hypotheses two is accepted. Eventually, through this article, an understanding that job satisfaction does not significantly influence to OCB but job satisfaction has significant influence to turnover intention.

  5. Quality of Working Life: An Antecedent to Employee Turnover Intention

    Science.gov (United States)

    Mosadeghrad, Ali Mohammad

    2013-01-01

    Background: The purpose of this study was to measure the level of quality of work life (QWL) among hospital employees in Iran. Additionally, it aimed to identify the factors that are critical to employees’ QWL. It also aimed to test a theoretical model of the relationship between employees’ QWL and their intention to leave the organization. Methods: A survey study was conducted based on a sample of 608 hospital employees using a validated questionnaire. Face, content and construct validity were conducted on the survey instrument. Results: Hospital employees reported low QWL. Employees were least satisfied with pay, benefits, job promotion, and management support. The most important predictor of QWL was management support, followed by job proud, job security and job stress. An inverse relationship was found between employees QWL and their turnover intention. Conclusion: This study empirically examined the relationships between employees’ QWL and their turnover intention. Managers can take appropriate actions to improve employees’ QWL and subsequently reduce employees’ turnover. PMID:24596835

  6. DNA turnover and strand breaks in Escherichia coli

    International Nuclear Information System (INIS)

    Hanawalt, P.; Grivell, A.; Nakayama, H.

    1975-01-01

    The extent of DNA turnover has been measured in a dnaB mutant of Escherichia coli, temperature sensitive for semiconservative DNA replication. At the nonpermissive temperature about 0.02 percent of the deoxynucleotides in DNA are exchanged per generation period. This turnover rate is markedly depressed in the presence of rifampicin. During thymine starvation strand breaks accumulate in the DNA of E. coli strains that are susceptible to thymineless death. Rifampicin suppresses the appearance of these breaks, consistent with our hypothesis that transcription may be accompanied by repairable single-strand breaks in DNA. DNA turnover is enhanced severalfold in strands containing 5-bromodeoxyuridine in place of thymidine, possibly because the analog (or the deoxyuridine, following debromination) is sometimes recognized and excised

  7. Firm-level innovation activity, employee turnover and HRM practices

    DEFF Research Database (Denmark)

    Eriksson, Tor; Qin, Zhihua; Wang, Wenjing

    2014-01-01

    ' innovation activities. Innovation is measured both by the number of ongoing projects and new commercialized products. The results show that higher R&D employee turnover is associated with a higher probability of being innovative, but decreases the intensity of innovation activities in innovating firms......This paper examines the relationship between employee turnover, HRM practices and innovation in Chinese firms in five high technology sectors. We estimate hurdle negative binomial models for count data on survey data allowing for analyses of the extensive as well as intensive margins of firms....... Innovating firms are more likely to have adopted high performance HRM practices, and the impact of employee turnover varies with the number of HRM practices implemented by the firm...

  8. 'Memory and molecular turnover,' 30 years after inception.

    Science.gov (United States)

    Meagher, Richard B

    2014-01-01

    In 1984 Sir Francis Crick hypothesized that memory is recorded in the brain as reversible modifications to DNA and protein, but acknowledged that most biomolecules turn over too rapidly to account for long-term memories. To accommodate this possible paradox he modeled an enzymatic mechanism to maintain modifications on hemi-modified multimeric symmetrical molecules. While studies on the turnover of chromatin modifications that may be involved in memory are in their infancy, an exploration of his model in the light of modern epigenetics produced somewhat surprising results. The molecular turnover rates for two classes of chromatin modifications believed to record and store durable memories were approximated from experiments using diverse approaches and were found to be remarkably short. The half-lives of DNA cytosine methylation and post-translationally modified nucleosomal histones are measured in hours and minutes, respectively, for a subset of sites on chromatin controlling gene expression. It appears likely that the turnover of DNA methylation in the brain and in neurons, in particular, is even more rapid than in other cell types and organs, perhaps accommodating neuronal plasticity, learning, and memory. The machinery responsible for the rapid turnover of DNA methylation and nucleosomal histone modifications is highly complex, partially redundant, and appears to act in a sequence specific manner. Molecular symmetry plays an important part in maintaining site-specific turnover, but its particular role in memory maintenance is unknown. Elucidating Crick's paradox, the contradiction between rapid molecular turnover of modified biomolecules and long-term memory storage, appears fundamental to understanding cognitive function and neurodegenerative disease.

  9. Peptide Level Turnover Measurements Enable the Study of Proteoform Dynamics.

    Science.gov (United States)

    Zecha, Jana; Meng, Chen; Zolg, Daniel Paul; Samaras, Patroklos; Wilhelm, Mathias; Kuster, Bernhard

    2018-05-01

    The coordination of protein synthesis and degradation regulating protein abundance is a fundamental process in cellular homeostasis. Today, mass spectrometry-based technologies allow determination of endogenous protein turnover on a proteome-wide scale. However, standard dynamic SILAC (Stable Isotope Labeling in Cell Culture) approaches can suffer from missing data across pulse time-points limiting the accuracy of such analysis. This issue is of particular relevance when studying protein stability at the level of proteoforms because often only single peptides distinguish between different protein products of the same gene. To address this shortcoming, we evaluated the merits of combining dynamic SILAC and tandem mass tag (TMT)-labeling of ten pulse time-points in a single experiment. Although the comparison to the standard dynamic SILAC method showed a high concordance of protein turnover rates, the pulsed SILAC-TMT approach yielded more comprehensive data (6000 proteins on average) without missing values. Replicate analysis further established that the same reproducibility of turnover rate determination can be obtained for peptides and proteins facilitating proteoform resolved investigation of protein stability. We provide several examples of differentially turned over splice variants and show that post-translational modifications can affect cellular protein half-lives. For example, N-terminally processed peptides exhibited both faster and slower turnover behavior compared with other peptides of the same protein. In addition, the suspected proteolytic processing of the fusion protein FAU was substantiated by measuring vastly different stabilities of the cleavage products. Furthermore, differential peptide turnover suggested a previously unknown mechanism of activity regulation by post-translational destabilization of cathepsin D as well as the DNA helicase BLM. Finally, our comprehensive data set facilitated a detailed evaluation of the impact of protein

  10. Peningkatan Komitmen Organisasi untuk Menurunkan Angka Turnover Karyawan

    Directory of Open Access Journals (Sweden)

    Elita Halimsetiono

    2014-05-01

    Full Text Available Komitmen organisasi dapat diartikan sebagai suatu sikap yang harus dimiliki oleh setiap pegawai untuk menunjukkan loyalitas terhadap organisasi tempat mereka bekerja. Pada dasarnya, komitmen organisasi berkaitan erat dengan aspek-aspek psikologis dalam menerima dan memercayai nilai-nilai dan tujuan organisasi yang muncul sebagai keinginan untuk tetap mempertahankan keanggotaan dalam organisasi. Permasalahan yang sering dikaitkan dengan rendahnya komitmen organisasi adalah pindah kerja (turnover. Masalah ini memiliki dampak yang merugikan organisasi karena dapat menghambat efektivitas dan efisiensi kerja yang selanjutnya akan menurunkan tingkat produktivitas organisasi. Oleh karena itu, untuk mencegah tingginya turnover karyawan, organisasi perlu meningkatkan komitmen organisasi karyawannya. Caranya adalah dengan mengetahui faktor-faktor apa saja yang memengaruhi komitmen organisasi dan bagaimana cara untuk meningkatkan komitmen organisasi tersebut. Artikel ini membahas faktor-faktor apa saja yang memengaruhi komitmen organisasi dan cara-cara yang dapat digunakan untuk meningkatkan komitmen organisasi sebagai upaya untuk menurunkan angka turnover karyawan. Organizational commitment can be interpreted as an attitude that should be owned by every employee to demonstrate loyalty to the organization where they work. Basically, organizational commitment is closely related to the psychological aspects in the acceptance and confidence to the values and objectives of the organization that are presented through the existence of a desire to maintain membership in the organization. Problems which are associated with low organizational commitment is turnover. This problem has an adverse impact on the organization because it can inhibit the effectiveness and efficiency of the work that would lower the level of productivity of the organization. Therefore, to prevent the high employee turnover, the organization should increase the organizational commitment of

  11. Stable isotopic constraints on global soil organic carbon turnover

    Directory of Open Access Journals (Sweden)

    C. Wang

    2018-02-01

    Full Text Available Carbon dioxide release during soil organic carbon (SOC turnover is a pivotal component of atmospheric CO2 concentrations and global climate change. However, reliably measuring SOC turnover rates on large spatial and temporal scales remains challenging. Here we use a natural carbon isotope approach, defined as beta (β, which was quantified from the δ13C of vegetation and soil reported in the literature (176 separate soil profiles, to examine large-scale controls of climate, soil physical properties and nutrients over patterns of SOC turnover across terrestrial biomes worldwide. We report a significant relationship between β and calculated soil C turnover rates (k, which were estimated by dividing soil heterotrophic respiration rates by SOC pools. ln( − β exhibits a significant linear relationship with mean annual temperature, but a more complex polynomial relationship with mean annual precipitation, implying strong-feedbacks of SOC turnover to climate changes. Soil nitrogen (N and clay content correlate strongly and positively with ln( − β, revealing the additional influence of nutrients and physical soil properties on SOC decomposition rates. Furthermore, a strong (R2 = 0.76; p < 0.001 linear relationship between ln( − β and estimates of litter and root decomposition rates suggests similar controls over rates of organic matter decay among the generalized soil C stocks. Overall, these findings demonstrate the utility of soil δ13C for independently benchmarking global models of soil C turnover and thereby improving predictions of multiple global change influences over terrestrial C-climate feedback.

  12. Human turnover dynamics during sleep: Statistical behavior and its modeling

    Science.gov (United States)

    Yoneyama, Mitsuru; Okuma, Yasuyuki; Utsumi, Hiroya; Terashi, Hiroo; Mitoma, Hiroshi

    2014-03-01

    Turnover is a typical intermittent body movement while asleep. Exploring its behavior may provide insights into the mechanisms and management of sleep. However, little is understood about the dynamic nature of turnover in healthy humans and how it can be modified in disease. Here we present a detailed analysis of turnover signals that are collected by accelerometry from healthy elderly subjects and age-matched patients with neurodegenerative disorders such as Parkinson's disease. In healthy subjects, the time intervals between consecutive turnover events exhibit a well-separated bimodal distribution with one mode at ⩽10 s and the other at ⩾100 s, whereas such bimodality tends to disappear in neurodegenerative patients. The discovery of bimodality and fine temporal structures (⩽10 s) is a contribution that is not revealed by conventional sleep recordings with less time resolution (≈30 s). Moreover, we estimate the scaling exponent of the interval fluctuations, which also shows a clear difference between healthy subjects and patients. We incorporate these experimental results into a computational model of human decision making. A decision is to be made at each simulation step between two choices: to keep on sleeping or to make a turnover, the selection of which is determined dynamically by comparing a pair of random numbers assigned to each choice. This decision is weighted by a single parameter that reflects the depth of sleep. The resulting simulated behavior accurately replicates many aspects of observed turnover patterns, including the appearance or disappearance of bimodality and leads to several predictions, suggesting that the depth parameter may be useful as a quantitative measure for differentiating between normal and pathological sleep. These findings have significant clinical implications and may pave the way for the development of practical sleep assessment technologies.

  13. High-performance ion chromatography method for separation and quantification of inositol phosphates in diets and digesta

    DEFF Research Database (Denmark)

    Blaabjerg, Karoline; Hansen-Møller, Jens; Poulsen, Hanne Damgaard

    2010-01-01

    A gradient high-performance ion chromatographic method for separation and quantification of inositol phosphates (InsP2-InsP6) in feedstuffs, diets, gastric and ileal digesta from pigs was developed and validated. The InsP2-InsP6 were separated on a Dionex CarboPacTM PA1 column using a gradient...... is not as aggressive as HCl. Twenty-three of the 27 separated inositol phosphate isomers were isolated. ICP-MS was used for quantification of phosphorus in the isolated isomers and used for calculation of correction factors for each isomer allowing InsP6 to be used as calibration standard. The detection limits for Ins......P2-InsP6 were in the range of 0.9-4.4 mg phosphorus L-1. The recovery of the major part of the inositol phosphates was 80-100%, and the CV for repeatability and reproducibility were 1-17% and 1-14%, respectively....

  14. Current Insights Into Inositol Isoforms, Mediterranean and Ketogenic Diets for Polycystic Ovary Syndrome: From Bench to Bedside.

    Science.gov (United States)

    Muscogiuri, Giovanna; Palomba, Stefano; Laganà, Antonio Simone; Orio, Francesco

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a complex syndrome characterized by reproductive and metabolic implications. Lifestyle changes, such as diet and exercise, are considered first-line treatment for women affected by PCOS. Pharmacologic treatments target the hormonal and metabolic dysregulations associated to the disease such as insulin resistance, anovulation, hirsutism and menstrual irregularities. To focus on the role of inositol isoforms, as well as Mediterranean and ketogenic diets, as possible therapeutic strategies in PCOS women. Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Accumulating evidence suggests that two inositol isoforms, myo- and D-chiro-, may play a pivotal role in re-addressing both hormonal and metabolic parameters toward homeostasis, counteracting the symptoms and signs typical of this syndrome. In addition, studies focused on Mediterranean and ketogenic diet provided positive results in patients affected by obesity and type 2 diabetes, so these dietetic regimens could represent a fascinating dietetic treatment for the management of PCOS. Both the isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS. In spite of accumulating evidence, it is currently not possible to draw firm conclusion(s) about the efficacy of these interventions considering the severe bias due to different samples size, dose, and duration of intervention among the published studies on this topic. Furthermore, future longitudinal cohort studies along with prospective interventional trials may contribute to better clarify the role of Mediterranean and ketogenic diets in the treatment of PCOS.

  15. Occurrence of myo-inositol and alkyl-substituted polysaccharide in the prey-trapping mucilage of Drosera capensis

    Science.gov (United States)

    Kokubun, Tetsuo

    2017-10-01

    The chemical composition of the exudate mucilage droplets of the carnivorous plant Drosera capensis was investigated using nuclear magnetic resonance spectroscopy. The mucilage was found to contain beside a very large molecular weight polysaccharide a significant amount of myo-inositol. It appears that myo-inositol escaped detection due to the commonly applied methodology on the chemical analysis of plant mucilage, such as dialysis, precipitation of polysaccharide component with alcohol, acid hydrolysis and detection of the resultant monosaccharide (aldose) units. The possible functions of myo-inositol in the mucilage droplets and the fate after being washed off from the leaf tentacles are proposed. On the polysaccharide component, the presence of methyl ester and alkyl chain-like moieties could be confirmed. These lipophilic moieties may provide the prey-trapping mucilage with the unique adhesive property onto the hydrophobic insect body parts, as well as onto the nature's well-known superhydrophobic surfaces such as the leaves of the sacred lotus plants. A re-evaluation of the mineral components of the mucilage, reported 40 years ago, is presented from the viewpoints of the current result and plants' natural habitat. A case for re-examination of the well-studied plant mucilaginous materials is made in light of the new findings.

  16. 2H-NMR studies of hypocotyl cell walls of germinating beans supplied with perdeuterated myo-inositol

    International Nuclear Information System (INIS)

    Sasaki, K.; Wallace, J.C.; MacKay, A.L.; Balza, F.; Taylor, I.E.P.

    1987-01-01

    When myo-[2- 3 H] inositol (MI) was supplied to bean seeds by imbibition, only uronic acid, arabinose and xylose residues of cell wall polysaccharides were labeled. To study the structural mobility of the uronic acid- and/or pentose-rich polysaccharides in cell wall using 2 H-NMR, the authors supplied perdeuterated MI with [2- 3 H] MI to germinating bean seeds. Perdeuterated MI was prepared by the 1 H- 2 H exchange reaction of MI in deuterium oxide with Raney nickel. During the exchange reaction, extensive epimerization occurred and at least 6 inositol epimers in addition to MI were identified in the reaction mixture of GC/MS. The perdeuterated MI was completely resolved from other inositol epimers and purified by anion-exchange chromatography using Dowex 1 (borate form) and by crystallization. The 2 H-NMR analysis resolved the 2 H-labeled hypocotyl cell walls into two components (rigid and mobile components). They also report the distribution of 2 H and 3 H from perdeuterated and [2- 3 H] MI in the cell wall sugar residues

  17. Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease.

    Science.gov (United States)

    Chang, H-H; Chao, H-N; Walker, C S; Choong, S-Y; Phillips, A; Loomes, K M

    2015-11-01

    Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (-51%)>diabetes mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease. Copyright © 2015 the American Physiological Society.

  18. Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial.

    Science.gov (United States)

    Rizzo, P; Raffone, E; Benedetto, V

    2010-06-01

    The aim of the study was to evaluate the efficacy of a treatment with myo-inositol plus folic acid plus melatonin compared with myo-inositol plus folic acid alone on oocyte quality in women underwent in vitro fertilization (IVF) cycles. A prospective, clinical trial. Starting on the day of GnRH administration, 65 women undergoing IVF cycles were randomized in two groups to receive myo-inositol plus folic acid plus melatonin (32 women, group A), and myo-inositol plus folic acid (33 women, group B), administered continuously. Primary endpoints were number of morphologically mature oocytes retrieved (MII oocytes), embryo quality, and pregnancy rate. Secondary endpoints were the total number of oocytes retrieved (immature and mature oocytes), fertilization rate per number of retrieved oocytes and embryo cleavage rate. The mean number of oocytes retrieved did not differ between the two groups (7.88 +/- 1.76 vs 7.67 +/- 1.88; P=0.65). Whereas the group cotreated with melatonin reported a significantly greater mean number of mature oocytes (6.56 +/- 1.64 vs 5.76 +/- 1.56; P=0.047) and a lower mean number of immature oocytes (1.31 +/- 0.74 vs. 1.91 +/- 0.68; P=0.001). The mean number of embyos of top-quality (class 1 and 2) resulted higher in the group A (1.69 +/- 0.64 vs 1.24 +/- 0.75; P=0.01). Fertilization rate did not differ between the two groups. A total of 22 pregnancies were obtained (13 in group A and 9 in group B; P=0.26). Clinical pregnancy rate and implantation rate were in tendency higher in the group cotreated with melatonin, although the differences did not reach statistical significance. Biochemical pregnancy rate and abortion rate were similar in both groups. melatonin ameliorates the activity of myo-inositol and folic acid by improving oocyte quality and pregnancy outcome in women with low oocyte quality history.

  19. Fat storage-inducing transmembrane (FIT or FITM proteins are related to lipid phosphatase/phosphotransferase enzymes

    Directory of Open Access Journals (Sweden)

    Matthew J Hayes

    2017-12-01

    Full Text Available Fat storage-inducing transmembrane (FIT or FITM proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known. Saccharomyces cerevisiae has two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline. This strongly suggests a role for Scs3p in phospholipid biosynthesis. Looking at the FITM family as widely as possible, we found that FITMs are widespread throughout eukaryotes, indicating presence in the last eukaryotic common ancestor. Protein alignments also showed that FITM sequences contain the active site of lipid phosphatase/phosphotransferase (LPT enzymes. This large family transfers phosphate-containing headgroups either between lipids or in exchange for water. We confirmed the prediction that FITMs are related to LPTs by showing that single amino-acid substitutions in the presumptive catalytic site prevented their ability to rescue growth of the mutants on low inositol/high choline media when over-expressed. The substitutions also prevented rescue of other phenotypes associated with loss of FITM in yeast, including mistargeting of Opi1p, defective ER morphology, and aberrant lipid droplet budding. These results suggest that Scs3p, Yft2p and FITMs in general are LPT enzymes involved in an as yet unknown critical step in phospholipid metabolism.

  20. Synthesis and turnover of purine nucleoside phosphorylase in human lymphocytes

    International Nuclear Information System (INIS)

    Snyder, F.F.; Kwan, E.; Mably, E.R.; Neote, K.

    1986-01-01

    The authors study the synthesis of purine nucleoside phosphorylase during phytohumagglutinin induced T cell transformation and have examined the turnover of purine nucleoside phosphorylase in thte human lymphoblast WI-L2. A polyclonal antibody to purine nucleoside phosphorylase in the synthetic and turnover studies is used. Fluorography of purine nucleoside phosphorylase immunoprecipitates from WI-L2 cells are shown. Lymphoblast proteins were labelled during 16hour cultrue with 4,5-tritium-leucine. Samples were 20 ug of total protein, immunoprecipitate of 200 ug protein with control serum and purine nucleoside phosphorylase antiserum

  1. Platelet monoamine oxidase: specific activity and turnover number in headache

    International Nuclear Information System (INIS)

    Summers, K.M.; Brown, G.K.; Craig, I.W.; Peatfield, R.; Rose, F.C.

    1982-01-01

    Monoamine oxidase turnover numbers (molecules of substrate converted to product per minute per active site) have been calculated for the human platelet enzyme using [ 3 H]pargyline. Headache patients with high and low monoamine oxidase specific activities relative to controls were found to have turnover numbers very close to those for controls. This finding suggests that their specific activities vary because of differences in the concentration of active monoamine oxidase molecules, rather than differences in the ability of those enzyme molecules to catalyse the deamination reaction. (Auth.)

  2. [Pharmaceutical logistic in turnover of pharmaceutical products of Azerbaijan].

    Science.gov (United States)

    Dzhalilova, K I

    2009-11-01

    Development of pharmaceutical logistic system model promotes optimal strategy for pharmaceutical functioning. The goal of such systems is organization of pharmaceutical product's turnover in required quantity and assortment, at preset time and place, at a highest possible degree of consumption readiness with minimal expenses and qualitative service. Organization of the optimal turnover chain in the region is offered to start from approximate classification of medicaments by logistic characteristics. Supplier selection was performed by evaluation of timeliness of delivery, quality of delivered products (according to the minimum acceptable level of quality) and time-keeping of time spending for orders delivery.

  3. Dietary arginine silicate inositol complex inhibits periodontal tissue loss in rats with ligature-induced periodontitis

    Directory of Open Access Journals (Sweden)

    Dundar S

    2016-11-01

    Full Text Available Serkan Dundar,1 Abubekir Eltas,2 Sema S Hakki,3 Sıddık Malkoc,4 M Ozay Uslu,2 Mehmet Tuzcu,5 James Komorowski,6 I Hanifi Ozercan,7 Fatih Akdemir,8 Kazim Sahin9 1Department of Periodontology, Faculty of Dentistry, Firat University, Elazig, 2Department of Periodontology, Faculty of Dentistry, Inonu University, Malatya, 3Department of Periodontology, Faculty of Dentistry, Selcuk University, Konya, 4Department of Orthodontics, Faculty of Dentistry, Inonu University, Malatya, 5Department of Biology, Faculty of Science, Firat University, Elazig, Turkey; 6Research & Development, Nutrition 21 Inc., Purchase, NY, USA; 7Department of Pathology, Faculty of Medicine, 8Department of Animal Nutrition, Faculty of Fisheries, Inonu University, Malatya, 9Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey Abstract: The purpose of this study was to induce experimental periodontitis in rats previously fed diets containing arginine silicate inositol (ASI complex and examine the biochemical, immunological, and radiological effects. Fifty two 8-week-old female Sprague Dawley rats were equally divided into four groups. The control group included those fed a standard rat diet with no operation performed during the experiment. The periodontitis, ASI I, and ASI II groups were subjected to experimental periodontitis induction for 11 days after being fed a standard rat diet alone, a diet containing 1.81 g/kg ASI complex, or a diet containing 3.62 g/kg ASI complex, respectively, for 8 weeks. Throughout the 11-day duration of periodontitis induction, all rats were fed standard feed. The rats were euthanized on the eleventh day, and their tissue and blood samples were collected. In the periodontitis group, elevated tissue destruction parameters and reduced tissue formation parameters were found, as compared to the ASI groups. Levels of enzymes, cytokines, and mediators associated with periodontal tissue destruction were lower

  4. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

    2005-01-01

    Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five...... conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

  5. The evolution of lipids

    Science.gov (United States)

    Itoh, Y. H.; Sugai, A.; Uda, I.; Itoh, T.

    2001-01-01

    Living organisms on the Earth which are divided into three major domains - Archaea, Bacteria, and Eucarya, probably came from a common ancestral cell. Because there are many thermophilic microorganisms near the root of the universal phylogenetic tree, the common ancestral cell should be considered to be a thermophilic microorganism. The existence of a cell is necessary for the living organisms; the cell membrane is the essential structural component of a cell, so its amphiphilic property is vital for the molecule of lipids for cell membranes. Tetraether type glycerophospholipids with C 40 isoprenoid chains are major membrane lipids widely distributed in archaeal cells. Cyclization number of C 40 isoprenoid chains in thermophilic archaea influences the fluidity of lipids whereas the number of carbons and degree of unsaturation in fatty acids do so in bacteria and eucarya. In addition to the cyclization of the tetraether lipids, covalent bonding of two C 40 isoprenoid chains was found in hyperthermophiles. These characteristic structures of the lipids seem to contribute to their fundamental physiological roles in hyperthermophiles. Stereochemical differences between G-1-P archaeal lipids and G-3-P bacterial and eucaryal lipids might have occured by the function of some proteins long after the first cell was developed by the reactions of small organic molecules. We propose that the structure of lipids of the common ancestral cell may have been similar to those of hyperthermophilic archaea.

  6. Lysosomal lipid storage diseases.

    Science.gov (United States)

    Schulze, Heike; Sandhoff, Konrad

    2011-06-01

    Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the help of lipid binding proteins in a sequential manner. Because of a functionally impaired hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease, cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome. In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the coprecipitation of other hydrophobic substances in the endolysosomal system, such as lipids and proteins, causing a "traffic jam." This can impair lysosomal function, such as delivery of nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic approaches are currently restricted to mild forms of diseases with significant residual catabolic activities and without brain involvement.

  7. Methane turnover and environmental change from Holocene biomarker records in a thermokarst lake in Arctic Alaska

    Science.gov (United States)

    Elvert, Marcus; Pohlman, John; Becker, Kevin W.; Gaglioti, Benjamin V.; Hinrichs, Kai-Uwe; Wooller, Matthew J.

    2016-01-01

    Arctic lakes and wetlands contribute a substantial amount of methane to the contemporary atmosphere, yet profound knowledge gaps remain regarding the intensity and climatic control of past methane emissions from this source. In this study, we reconstruct methane turnover and environmental conditions, including estimates of mean annual and summer temperature, from a thermokarst lake (Lake Qalluuraq) on the Arctic Coastal Plain of northern Alaska for the Holocene by using source-specific lipid biomarkers preserved in a radiocarbon-dated sediment core. Our results document a more prominent role for methane in the carbon cycle when the lake basin was an emergent fen habitat between ~12,300 and ~10,000 cal yr BP, a time period closely coinciding with the Holocene Thermal Maximum (HTM) in North Alaska. Enhanced methane turnover was stimulated by relatively warm temperatures, increased moisture, nutrient supply, and primary productivity. After ~10,000 cal yr BP, a thermokarst lake with abundant submerged mosses evolved, and through the mid-Holocene temperatures were approximately 3°C cooler. Under these conditions, organic matter decomposition was attenuated, which facilitated the accumulation of submerged mosses within a shallower Lake Qalluuraq. Reduced methane assimilation into biomass during the mid-Holocene suggests that thermokarst lakes are carbon sinks during cold periods. In the late-Holocene from ~2700 cal yr BP to the most recent time, however, temperatures and carbon deposition rose and methane oxidation intensified, indicating that more rapid organic matter decomposition and enhanced methane production could amplify climate feedback via potential methane emissions in the future.

  8. Distribution of Inositol 1,4,5-Trisphosphate Receptors in Rat Osteoclasts

    International Nuclear Information System (INIS)

    Morikawa, Kazumasa; Goto, Tetsuya; Tanimura, Akihiko; Kobayashi, Shigeru; Maki, Kenshi

    2008-01-01

    Inositol 1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs) are Ca 2+ channels that localize to intracellular Ca 2+ stores such as the endoplasmic reticulum (ER). Recently, IP 3 Rs were found to participate in the formation of the cytoskeleton and cellular adhesions. In this study, we examined the cellular localization of type I, II, and III IP 3 Rs to assess their role in cellular adhesion in rat osteoclasts. Rat bone marrow cells were cultured in α-MEM with 10% fetal bovine serum, M-CSF, RANKL, and 1,25(OH) 2 D 3 for 1 week to promote osteoclast formation. Type I, II, and III IP 3 R expression in the osteoclasts was then examined by RT-PCR. Double-staining was performed using antibodies against type I, II, and III IP 3 Rs and DiOC 6 , an ER marker, or TRITC-phalloidin, an actin filament marker. Expression of all three IP 3 Rs was detected in the newly formed osteoclasts; however, the localization of the type I and II IP 3 Rs was predominantly close to nuclear, and possibly colocalized with the ER, while the type III IP 3 Rs were localized to the ER and podosomes, actin-rich adhesion structures in osteoclasts. These findings suggest that type III IP 3 Rs are associated with osteoclast adhesion

  9. Treating Woman with Myo-Inositol Vaginal Suppositories Improves Partner’s Sperm Motility and Fertility

    Directory of Open Access Journals (Sweden)

    Mario Montanino Oliva

    2016-01-01

    Full Text Available Motility is the feature that allows spermatozoa to actively reach and penetrate the female gamete during fertilization. When this function is altered, and especially decreased, troubles in conceiving may occur. In this study, we demonstrated that treating fertile women with myo-inositol (MI vaginal suppositories ameliorated their partners’ sperm motility and also positively affected their conceiving capacity, without changes in cervical mucus structural and biochemical characteristics. Indeed, by means of the postcoital test on female cervical mucus, a significant improvement especially in progressive sperm motility was recorded after MI suppository use. Concomitantly, after MI treatment, a reduction of immotile spermatozoa percentage was observed. Importantly, MI vaginal supplementation positively correlated with a pregnancy for 5 of the 50 couples enrolled in the study, leading us to speculate that this substance may substantially contribute to create in the cervical mucus an ideal milieu that makes spermatozoa more motile and functionally able to fertilize. Even though the detailed mechanism is still unclear, these results should encourage MI vaginal use for the clinical improvement of male infertility, through their partners.

  10. Age-associated repression of type 1 inositol 1, 4, 5-triphosphate receptor impairs muscle regeneration

    Science.gov (United States)

    Lee, Bora; Lee, Seung-Min; Bahn, Young Jae; Lee, Kwang-Pyo; Kang, Moonkyung; Kim, Yeon-Soo; Woo, Sun-Hee; Lim, Jae-Young; Kim, Eunhee; Kwon, Ki-Sun

    2016-01-01

    Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5-triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA-expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies. PMID:27658230

  11. Evaluation of the effect of Retrograde Intrarenal Surgery with Myo-Inositol Oxygenase

    Science.gov (United States)

    Mertoglu, Cuma; Bozkurt, Aliseydi; Keskin, Ercüment; Gunay, Murat

    2018-01-01

    Objective: To investigate the effect of retrograde intra-renal surgery (RIRS) on kidneys using the myo-inositol oxygenase (MIOX) enzyme. MIOX is a renal tubular-specific novel marker for the early diagnosis of acute kidney injury. Methods: A total of twenty seven individuals that had undergone RIRS to treat kidney stones were included in the study. Biochemical tests were performed on serum samples collected immediately before RIRS (hour 0) and at the 6th and 24th hours after the surgery. Results: The creatinine value at hour 6 was lower than the baseline (hour 0) value (p = 0.0305). Cystatin C at hour 6 was lower than the value measured at hour 24 (p = 0.0142). Similarly, MIOX was lower at hour 6 compared to hour 24 (p = 0.0214). MIOX/creatinine at hour 6 was lower than the value calculated at hour 24 (p = 0.0348). The basal values of MIOX and creatinine were found to have a positive correlation (correlation coefficient r = 0.5946, p = 0.0035). Conclusions: Similar to the serum creatinine, the serum MIOX level provides information about kidney functions. RIRS was confirmed to be a safe procedure for the treatment of acute kidney injury with no negative effects on the kidneys. PMID:29643901

  12. Quantification of inositol phosphates in almond meal and almond brown skins by HPLC/ESI/MS.

    Science.gov (United States)

    Duong, Quynh H; Clark, Kevin D; Lapsley, Karen G; Pegg, Ronald B

    2017-08-15

    The extraction and measurement of all six forms of inositol phosphates (InsPs) in almond meal and brown skins were improved from existing methods by pH adjustment, supplementation of EDTA, and rapid analysis via anion-exchange high-performance liquid chromatography coupled with electrospray ionization mass spectrometry. The quantity of InsPs in six major almond cultivars ranged from 8 to 12μmol/g in the meal and 5 to 14μmol/g in the brown skins. InsP 6 was the dominant form, but lower forms still accounted for ∼20% of the total InsPs molar concentration in a majority of the samples. InsPs contributed 32-55% of the organic phosphorus content and 20-38% of the total phosphorus content in the meal. In brown skins, these ranges were 44-77% and 30-52%, respectively. The successful application of this analytical method with almonds demonstrates its potential use for re-examination of the reported phytic acid contents in many other tree nuts, legumes, grains, and complex foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.

    Science.gov (United States)

    Wang, Liwei; Wagner, Larry E; Alzayady, Kamil J; Yule, David I

    2017-07-14

    The inositol 1,4,5 trisphosphate receptor (IP 3 R) is an intracellular Ca 2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP 3 R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP 3 R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP 3 binding despite the loss of peptide continuity. In this study, we demonstrate that region-specific receptor fragmentation modifies channel regulation. Specifically, the agonist-evoked temporal Ca 2+ release profile and protein kinase A modulation of Ca 2+ release are markedly altered. Moreover, we also demonstrate that activation of fragmented IP 3 R1 can result in a distinct functional outcome. Our work suggests that proteolysis of IP 3 R1 may represent a novel form of modulation of IP 3 R1 channel function and increases the repertoire of Ca 2+ signals achievable through this channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. HLH-29 regulates ovulation in C. elegans by targeting genes in the inositol triphosphate signaling pathway

    Directory of Open Access Journals (Sweden)

    Ana White

    2012-02-01

    The reproductive cycle in the nematode Caenorhabditis elegans depends in part on the ability of the mature oocyte to ovulate into the spermatheca, fuse with the sperm during fertilization, and then exit the spermatheca as a fertilized egg. This cycle requires the integration of signals between the germ cells and the somatic gonad and relies heavily on the precise control of inositol 1,4,5 triphosphate (IP3levels. The HLH-29 protein, one of five Hairy/Enhancer of Split (HES homologs in C. elegans, was previously shown to affect development of the somatic gonad. Here we show that HLH-29 expression in the adult spermatheca is strongly localized to the distal spermatheca valve and to the spermatheca-uterine valve, and that loss of hlh-29 activity interferes with oocyte entry into and egg exit from the spermatheca. We show that HLH-29 can regulate the transcriptional activity of the IP3 signaling pathway genes ppk-1, ipp-5, and plc-1 and provide evidence that hlh-29 acts in a genetic pathway with each of these genes. We propose that the HES-like protein HLH-29 acts in the spermatheca of larval and adult animals to effectively increase IP3 levels during the reproductive cycle.

  15. Involvement of Arabidopsis Hexokinase1 in Cell Death Mediated by Myo -Inositol Accumulation

    KAUST Repository

    Bruggeman, Quentin

    2015-06-05

    Programmed cell death (PCD) is essential for several aspects of plant life, including development and stress responses. We recently identified the mips1 mutant of Arabidopsis thaliana, which is deficient for the enzyme catalyzing the limiting step of myo-inositol (MI) synthesis. One of the most striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD. Here, we identified a suppressor of PCD by screening for mutations that abolish the mips1 cell death phenotype. Our screen identified the hxk1 mutant, mutated in the gene encoding the hexokinase1 (HXK1) enzyme that catalyzes sugar phosphorylation and acts as a genuine glucose sensor. We show that HXK1 is required for lesion formation in mips1 due to alterations in MI content, via SA-dependant signaling. Using two catalytically inactive HXK1 mutants, we also show that hexokinase catalytic activity is necessary for the establishment of lesions in mips1. Gas chromatography-mass spectrometry analyses revealed a restoration of the MI content in mips1 hxk1 that it is due to the activity of the MIPS2 isoform, while MIPS3 is not involved. Our work defines a pathway of HXK1-mediated cell death in plants and demonstrates that two MIPS enzymes act cooperatively under a particular metabolic status, highlighting a novel checkpoint of MI homeostasis in plants. © 2015 American Society of Plant Biologists. All rights reserved.

  16. Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.

    Science.gov (United States)

    Takada, Silvia Honda; Ikebara, Juliane Midori; de Sousa, Erica; Cardoso, Débora Sterzeck; Resende, Rodrigo Ribeiro; Ulrich, Henning; Rückl, Martin; Rüdiger, Sten; Kihara, Alexandre Hiroaki

    2017-11-01

    It is well known that calcium (Ca 2+ ) is involved in the triggering of neuronal death. Ca 2+ cytosolic levels are regulated by Ca 2+ release from internal stores located in organelles, such as the endoplasmic reticulum. Indeed, Ca 2+ transit from distinct cell compartments follows complex dynamics that are mediated by specific receptors, notably inositol trisphosphate receptors (IP3Rs). Ca 2+ release by IP3Rs plays essential roles in several neurological disorders; however, details of these processes are poorly understood. Moreover, recent studies have shown that subcellular location, molecular identity, and density of IP3Rs profoundly affect Ca 2+ transit in neurons. Therefore, regulation of IP3R gene products in specific cellular vicinities seems to be crucial in a wide range of cellular processes from neuroprotection to neurodegeneration. In this regard, microRNAs seem to govern not only IP3Rs translation levels but also subcellular accumulation. Combining new data from molecular cell biology with mathematical modelling, we were able to summarize the state of the art on this topic. In addition to presenting how Ca 2+ dynamics mediated by IP3R activation follow a stochastic regimen, we integrated a theoretical approach in an easy-to-apply, cell biology-coherent fashion. Following the presented premises and in contrast to previously tested hypotheses, Ca 2+ released by IP3Rs may play different roles in specific neurological diseases, including Alzheimer's disease and Parkinson's disease.

  17. Structure-Function Analysis of Inositol Hexakisphosphate-induced Autoprocessing in Clostridium difficile Toxin A

    Energy Technology Data Exchange (ETDEWEB)

    Pruitt, Rory N.; Chagot, Benjamin; Cover, Michael; Chazin, Walter J.; Spiller, Ben; Lacy, D. Borden; (Vanderbilt)

    2009-09-25

    The action of Clostridium difficile toxins A and B depends on inactivation of host small G-proteins by glucosylation. Cellular inositol hexakisphosphate (InsP6) induces an autocatalytic cleavage of the toxins, releasing an N-terminal glucosyltransferase domain into the host cell cytosol. We have defined the cysteine protease domain (CPD) responsible for autoprocessing within toxin A (TcdA) and report the 1.6 {angstrom} x-ray crystal structure of the domain bound to InsP6. InsP6 is bound in a highly basic pocket that is separated from an unusual active site by a {beta}-flap structure. Functional studies confirm an intramolecular mechanism of cleavage and highlight specific residues required for InsP6-induced TcdA processing. Analysis of the structural and functional data in the context of sequences from similar and diverse origins highlights a C-terminal extension and a {pi}-cation interaction within the {beta}-flap that appear to be unique among the large clostridial cytotoxins.

  18. Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.

    Directory of Open Access Journals (Sweden)

    Takaaki Inaba

    Full Text Available Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice. We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.

  19. Novel structural features of the immunocompetent ceramide phospho-inositol glycan core from Trichomonas vaginalis.

    Science.gov (United States)

    Heiss, Christian; Wang, Zhirui; Black, Ian; Azadi, Parastoo; Fichorova, Raina N; Singh, Bibhuti N

    2016-01-01

    The ceramide phosphoinositol glycan core (CPI-GC) of the lipophosphoglycan of Trichomonas vaginalis is a major virulent factor of this common genitourinary parasite. While its carbohydrate composition has been reported before, its structure has remained largely unknown. We isolated the glycan portions of CPI-GC by nitrous acid deamination and hydrofluoric acid treatment and investigated their structures by methylation analysis and 1- and 2-D NMR. We found that the α-anomer of galactose is a major constituent of CPI-GC. The β-anomer was found exclusively at the non-reducing end of CPI-GC side chains. Furthermore the data showed that the rhamnan backbone is more complex than previously thought and that the inositol residue at the reducing end is linked to a 4-linked α-glucuronic acid (GlcA) residue. This appears to be the most striking and novel feature of this GPI-anchor type molecule. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Dietary arginine silicate inositol complex inhibits periodontal tissue loss in rats with ligature-induced periodontitis.

    Science.gov (United States)

    Dundar, Serkan; Eltas, Abubekir; Hakki, Sema S; Malkoc, Sıddık; Uslu, M Ozay; Tuzcu, Mehmet; Komorowski, James; Ozercan, I Hanifi; Akdemir, Fatih; Sahin, Kazim

    2016-01-01

    The purpose of this study was to induce experimental periodontitis in rats previously fed diets containing arginine silicate inositol (ASI) complex and examine the biochemical, immunological, and radiological effects. Fifty two 8-week-old female Sprague Dawley rats were equally divided into four groups. The control group included those fed a standard rat diet with no operation performed during the experiment. The periodontitis, ASI I, and ASI II groups were subjected to experimental periodontitis induction for 11 days after being fed a standard rat diet alone, a diet containing 1.81 g/kg ASI complex, or a diet containing 3.62 g/kg ASI complex, respectively, for 8 weeks. Throughout the 11-day duration of periodontitis induction, all rats were fed standard feed. The rats were euthanized on the eleventh day, and their tissue and blood samples were collected. In the periodontitis group, elevated tissue destruction parameters and reduced tissue formation parameters were found, as compared to the ASI groups. Levels of enzymes, cytokines, and mediators associated with periodontal tissue destruction were lower in rats fed a diet containing ASI complex after experimental periodontitis. These results indicate that ASI complex could be an alternative agent for host modulation.