Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action

DEFF Research Database (Denmark)

Faerch, K; Vaag, A; Holst, Jens Juul

2008-01-01

.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p > or = 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion x insulin sensitivity) during IVGTT (DI(IVGTT))) was reduced......AIMS/HYPOTHESIS: The impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic...

Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

DEFF Research Database (Denmark)

Rask, E; Olsson, T; Söderberg, S

2004-01-01

of glucose, insulin, C-peptide, GLP-1, and GIP. Insulin secretion (TIS) and insulin sensitivity (OGIS) were assessed using models describing the relationship between glucose, insulin and C-peptide data. These models allowed estimation also of the hepatic extraction of insulin. The age (54.2 +/- 9.7 [mean......Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects...... over the whole 180-minute period was higher in IGT (26.2 +/- 2.4 v 20.0 +/- 2.0 nmol/L; P =.035). Hepatic insulin extraction correlated linearly with OGIS (r = 0.71; P

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

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Lakshmanan, J; Landel, C P

1986-07-01

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

p53- and ERK7-dependent ribosome surveillance response regulates Drosophila insulin-like peptide secretion.

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Kiran Hasygar

2014-11-01

Full Text Available Insulin-like signalling is a conserved mechanism that coordinates animal growth and metabolism with nutrient status. In Drosophila, insulin-producing median neurosecretory cells (IPCs regulate larval growth by secreting insulin-like peptides (dILPs in a diet-dependent manner. Previous studies have shown that nutrition affects dILP secretion through humoral signals derived from the fat body. Here we uncover a novel mechanism that operates cell autonomously in the IPCs to regulate dILP secretion. We observed that impairment of ribosome biogenesis specifically in the IPCs strongly inhibits dILP secretion, which consequently leads to reduced body size and a delay in larval development. This response is dependent on p53, a known surveillance factor for ribosome biogenesis. A downstream effector of this growth inhibitory response is an atypical MAP kinase ERK7 (ERK8/MAPK15, which is upregulated in the IPCs following impaired ribosome biogenesis as well as starvation. We show that ERK7 is sufficient and essential to inhibit dILP secretion upon impaired ribosome biogenesis, and it acts epistatically to p53. Moreover, we provide evidence that p53 and ERK7 contribute to the inhibition of dILP secretion upon starvation. Thus, we conclude that a cell autonomous ribosome surveillance response, which leads to upregulation of ERK7, inhibits dILP secretion to impede tissue growth under limiting dietary conditions.

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

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Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

2003-01-01

of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

Secretion of alpha 2-plasmin inhibitor is impaired by amino acid deletion in a small region of the molecule.

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Toyota, S; Hirosawa, S; Aoki, N

1994-02-01

Alpha 2-plasmin inhibitor (alpha 2PI) deficiency Okinawa results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of the deletion of Glu137 in the amino acid sequence of alpha 2PI. To examine the effects of replacing the amino acid occupying position 137 or deleting its neighboring amino acid on alpha 2PI secretion, we used oligonucleotide-directed mutagenesis of alpha 2PI cDNA to change the codon specifying Glu137 or delete a codon specifying its neighboring amino acid. The effects were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of media from transiently transfected COS-7 cells. Replacement of Glu137 with an amino acid other than Cys had little effect on alpha 2PI secretion. In contrast, deletion of an amino acid in a region spanning a sequence of less than 30 amino acids including positions 127 and 137 severely impaired the secretion. The results suggest that structural integrity of the region, rather than its component amino acids, is important for the intracellular transport and secretion of alpha 2PI.

Mitochondrial Dysfunction Contributes to Impaired Insulin Secretion in INS-1 Cells with Dominant-negative Mutations of HNF-1α and in HNF-1α-deficient Islets*

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Pongratz, Rebecca L.; Kibbey, Richard G.; Kirkpatrick, Clare L.; Zhao, Xiaojian; Pontoglio, Marco; Yaniv, Moshe; Wollheim, Claes B.; Shulman, Gerald I.; Cline, Gary W.

2009-01-01

Maturity Onset Diabetes of the Young-type 3 (MODY-3) has been linked to mutations in the transcription factor hepatic nuclear factor (HNF)-1α, resulting in deficiency in glucose-stimulated insulin secretion. In INS-1 cells overexpressing doxycycline-inducible HNF-1α dominant-negative (DN-) gene mutations, and islets from Hnf-1α knock-out mice, insulin secretion was impaired in response to glucose (15 mm) and other nutrient secretagogues. Decreased rates of insulin secretion in response to glutamine plus leucine and to methyl pyruvate, but not potassium depolarization, indicate defects specific to mitochondrial metabolism. To identify the biochemical mechanisms responsible for impaired insulin secretion, we used 31P NMR measured mitochondrial ATP synthesis (distinct from glycolytic ATP synthesis) together with oxygen consumption measurements to determine the efficiency of mitochondrial oxidative phosphorylation. Mitochondrial uncoupling was significantly higher in DN-HNF-1α cells, such that rates of ATP synthesis were decreased by approximately one-half in response to the secretagogues glucose, glutamine plus leucine, or pyruvate. In addition to closure of the ATP-sensitive K+ channels with mitochondrial ATP synthesis, mitochondrial production of second messengers through increased anaplerotic flux has been shown to be critical for coupling metabolism to insulin secretion. 13C-Isotopomer analysis and tandem mass spectrometry measurement of Krebs cycle intermediates revealed a negative impact of DN-HNF-1α and Hnf-1α knock-out on mitochondrial second messenger production with glucose but not amino acids. Taken together, these results indicate that, in addition to reduced glycolytic flux, uncoupling of mitochondrial oxidative phosphorylation contributes to impaired nutrient-stimulated insulin secretion with either mutations or loss of HNF-1α. PMID:19376774

Methylglyoxal Impairs Insulin Secretion of Pancreatic β-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs

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Jinshuang Bo

2016-01-01

Full Text Available Methylglyoxal (MG is a highly reactive glucose metabolic intermediate and a major precursor of advanced glycation end products. MG level is elevated in hyperglycemic disorders such as diabetes mellitus. Substantial evidence has shown that MG is involved in the pathogenesis of diabetes and diabetic complications. We investigated the impact of MG on insulin secretion by MIN6 and INS-1 cells and the potential mechanisms of this effect. Our study demonstrates that MG impaired insulin secretion by MIN6 or ISN-1 cells in a dose-dependent manner. It increased reactive oxygen species (ROS production and apoptosis rate in MIN6 or ISN-1 cells and inhibited mitochondrial membrane potential (MMP and ATP production. Furthermore, the expression of UCP2, JNK, and P38 as well as the phosphorylation JNK and P38 was increased by MG. These effects of MG were attenuated by MG scavenger N-acetyl cysteine. Collectively, these data indicate that MG impairs insulin secretion of pancreatic β-cells through increasing ROS production. High levels of ROS can damage β-cells directly via JNK/P38 upregulation and through activation of UCP2 resulting in reduced MMP and ATP production, leading to β-cell dysfunction and impairment of insulin production.

Mitochondrial Dysfunction Contributes to Impaired Insulin Secretion in INS-1 Cells with Dominant-negative Mutations of HNF-1α and in HNF-1α-deficient Islets*

OpenAIRE

Pongratz, Rebecca L.; Kibbey, Richard G.; Kirkpatrick, Clare L.; Zhao, Xiaojian; Pontoglio, Marco; Yaniv, Moshe; Wollheim, Claes B.; Shulman, Gerald I.; Cline, Gary W.

2009-01-01

Maturity Onset Diabetes of the Young-type 3 (MODY-3) has been linked to mutations in the transcription factor hepatic nuclear factor (HNF)-1α, resulting in deficiency in glucose-stimulated insulin secretion. In INS-1 cells overexpressing doxycycline-inducible HNF-1α dominant-negative (DN-) gene mutations, and islets from Hnf-1α knock-out mice, insulin secretion was impaired in response to glucose (15 mm) and other nutrient secretagogues. Decreased rates of insulin secretion in response to glu...

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.

Science.gov (United States)

Bouchlariotou, Sofia; Liakopoulos, Vassilios; Giannopoulou, Myrto; Arampatzis, Spyridon; Eleftheriadis, Theodoros; Mertens, Peter R; Zintzaras, Elias; Messinis, Ioannis E; Stefanidis, Ioannis

2014-08-01

Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, pcircadian BP rhythm status ascribed this finding exclusively to non-dippers (pcircadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.

Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure.

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El Asmar, Ramzi; Panigrahi, Pinaki; Bamford, Penelope; Berti, Irene; Not, Tarcisio; Coppa, Giovanni V; Catassi, Carlo; Fasano, Alessio; El Asmar, Rahzi

2002-11-01

Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability. Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers. Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex. This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine.

Incretins, insulin secretion and Type 2 diabetes mellitus

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Vilsbøll, Tina; Holst, Jens Møller

2004-01-01

the genes encoding their receptors have been deleted. In patients with Type 2 diabetes, the incretin effect is either greatly impaired or absent, and it is assumed that this could contribute to the inability of these patients to adjust their insulin secretion to their needs. In studies of the mechanism...... of the impaired incretin effect in Type 2 diabetic patients, it has been found that the secretion of GIP is generally normal, whereas the secretion of GLP-1 is reduced, presumably as a consequence of the diabetic state. It might be of even greater importance that the effect of GLP-1 is preserved whereas...... the effect of GIP is severely impaired. The impaired GIP effect seems to have a genetic background, but could be aggravated by the diabetic state. The preserved effect of GLP-1 has inspired attempts to treat Type 2 diabetes with GLP-1 or analogues thereof, and intravenous GLP-1 administration has been shown...

Incretins, insulin secretion and Type 2 diabetes mellitus

DEFF Research Database (Denmark)

Vilsbøll, T; Holst, Jens Juul

2004-01-01

the effect of GIP is severely impaired. The impaired GIP effect seems to have a genetic background, but could be aggravated by the diabetic state. The preserved effect of GLP-1 has inspired attempts to treat Type 2 diabetes with GLP-1 or analogues thereof, and intravenous GLP-1 administration has been shown...... the genes encoding their receptors have been deleted. In patients with Type 2 diabetes, the incretin effect is either greatly impaired or absent, and it is assumed that this could contribute to the inability of these patients to adjust their insulin secretion to their needs. In studies of the mechanism...... of the impaired incretin effect in Type 2 diabetic patients, it has been found that the secretion of GIP is generally normal, whereas the secretion of GLP-1 is reduced, presumably as a consequence of the diabetic state. It might be of even greater importance that the effect of GLP-1 is preserved whereas...

System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

Science.gov (United States)

Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

2014-03-01

The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

[Changes in the secretion of somatotropin and insulin in hyperthyroidism].

Science.gov (United States)

Cavagnini, F; Peracchi, M; Panerai, A E; Pinto, M

1975-06-01

Twenty hyperthyroid patients were investigated for growth hormone (GH) and immunoreactive insulin (IRI) secretion in response to insulin hypoglycaemia, arginine infusion and glucose-induced hyperglycaemia. GH response to either insulin hypoglycaemia or arginine infusion was significantly reduced in these patients compared with 20 normal subjects. Thyrotoxic patients also displayed an abnormal GH pattern after a 100 g oral glucose load: in fact, serum GH underwent a paradoxical increase in spite of abnormally high levels attained by blood glucose. IRI secretion was also clearly reduced in response to arginine infusion and moderately blunted after oral glucose. In a group of patients re-evaluated under euthyroid conditions, a fair increase of GH response to the provocative stimuli jointly with the restoration of a normal suppressibility of serum GH by glucose were noted; by contrast, no significant change of IRI response to arginine or glucose took place. Likewise, the impairment of glucose tolerance was not improved. These findings indicate that an impairment of GH and IRI secretion is present in hyperthyroidism. The possibility that a potentiation of the catecholamine effects caused by the thyroid hormones is involved in this alteration deserves consideration.

GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion

DEFF Research Database (Denmark)

Cani, Patrice D; Holst, Jens Juul; Drucker, Daniel J

2007-01-01

to those described for beta-cells, brain and hepatoportal sensors. We determined the role of GLUT2, GLP-1 or GIP receptors in glucose-induced incretins secretion, in the corresponding knockout mice. GLP-1 secretion was reduced in all mutant mice, while GIP secretion did not require GLUT2. Intestinal GLP-1...... content was reduced only in GIP and GLUT2 receptors knockout mice suggesting that this impairment could contribute to the phenotype. Intestinal GIP content was similar in all mice studied. Furthermore, the impaired incretins secretion was associated with a reduced glucose-stimulated insulin secretion...

Species-specific sensitivity to selenium-induced impairment of cortisol secretion in adrenocortical cells of rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis)

International Nuclear Information System (INIS)

Miller, L.L.; Hontela, A.

2011-01-01

Species differences in physiological and biochemical attributes exist even among closely related species and may underlie species-specific sensitivity to toxicants. Rainbow trout (RT) are more sensitive than brook trout (BT) to the teratogenic effects of selenium (Se), but it is not known whether all tissues exhibit this pattern of vulnerability. In this study, primary cultures of RT and BT adrenocortical cells were exposed to selenite (Na 2 SO 3 ) and selenomethionine (Se-Met) to compare cell viability and ACTH-stimulated cortisol secretion in the two fish species. Cortisol, the primary stress hormone in fish, facilitates maintenance of homeostasis when fish are exposed to stressors, including toxicants. Cell viability was not affected by Se, but selenite impaired cortisol secretion, while Se-Met did not (RT and BT EC 50 > 2000 mg/L). RT cells were more sensitive (EC 50 = 8.7 mg/L) to selenite than BT cells (EC 50 = 90.4 mg/L). To identify the targets where Se disrupts cortisol synthesis, selenite-impaired RT and BT cells were stimulated with ACTH, dbcAMP, OH-cholesterol, and pregnenolone. Selenite acted at different steps in the cortisol biosynthesis pathway in RT and BT cells, confirming a species-specific toxicity mechanism. To test the hypothesis that oxidative stress mediates Se-induced toxicity, selenite-impaired RT cells were exposed to NAC, BSO and antioxidants (DETCA, ATA, Vit A, and Vit E). Inhibition of SOD by DETCA enhanced selenite-induced cortisol impairment, indicating that oxidative stress plays a role in Se toxicity; however, modifying GSH content of the cells did not have an effect. The results of this study, with two closely related salmonids, provided additional evidence for species-specific differences in sensitivity to Se which should be considered when setting thresholds and water quality guidelines. - Research Highlights: → We investigated species-specific sensitivity to Se in trout adrenocortical cells. → Selenite, not Se-Met, disrupts

Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

Science.gov (United States)

Dayeh, Tasnim; Ling, Charlotte

2015-10-01

β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.

Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation.

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Nils Paulmann

2009-10-01

Full Text Available While serotonin (5-HT co-localization with insulin in granules of pancreatic beta-cells was demonstrated more than three decades ago, its physiological role in the etiology of diabetes is still unclear. We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/- and 5-HT to show that intracellular 5-HT regulates insulin secretion. We found that these mice are diabetic and have an impaired insulin secretion due to the lack of 5-HT in the pancreas. The pharmacological restoration of peripheral 5-HT levels rescued the impaired insulin secretion in vivo. These findings were further evidenced by patch clamp experiments with isolated Tph1-/- beta-cells, which clearly showed that the secretory defect is downstream of Ca(2+-signaling and can be rescued by direct intracellular application of 5-HT via the clamp pipette. In elucidating the underlying mechanism further, we demonstrate the covalent coupling of 5-HT by transglutaminases during insulin exocytosis to two key players in insulin secretion, the small GTPases Rab3a and Rab27a. This renders them constitutively active in a receptor-independent signaling mechanism we have recently termed serotonylation. Concordantly, an inhibition of such activating serotonylation in beta-cells abates insulin secretion. We also observed inactivation of serotonylated Rab3a by enhanced proteasomal degradation, which is in line with the inactivation of other serotonylated GTPases. Our results demonstrate that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic beta-cells and suggest that intracellular 5-HT functions in various microenvironments via this mechanism in concert with the known receptor-mediated signaling.

Impaired crosstalk between pulsatile insulin and glucagon secretion in prediabetic individuals

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Rohrer, Stefan; Menge, Björn A; Grüber, Lena

2012-01-01

Postprandial hyperglucagonemia is frequently found in patients with diabetes. Recently, a loss of the inverse relationship between pulsatile insulin and glucagon secretion has been reported in patients with type 2 diabetes. The crosstalk between pulsatile islet hormone secretion in prediabetic...

Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the β-cell line INS-1E

International Nuclear Information System (INIS)

Piaggi, Simona; Novelli, Michela; Martino, Luisa; Masini, Matilde; Raggi, Chiara; Orciuolo, Enrico; Masiello, Pellegrino; Casini, Alessandro; De Tata, Vincenzo

2007-01-01

The aim of this research was to characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the insulin-secreting β-cell line INS-1E. A sharp decline of cell survival (below 20%) was observed after 1 h exposure to TCDD concentrations between 12.5 and 25 nM. Ultrastructurally, β-cell death was characterized by extensive degranulation, appearance of autophagic vacuoles, and peripheral nuclear condensation. Cytotoxic concentrations of TCDD rapidly induced a dose-dependent increase in intracellular calcium concentration. Blocking calcium entry by EGTA significantly decreased TCDD cytotoxicity. TCDD was also able to rapidly induce mitochondrial depolarization. Interestingly, 1 h exposition of INS-1E cells to very low TCDD concentrations (0.05-1 nM) dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct β-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lower than these. On the basis of this latter observation we suggest that pancreatic β-cells could be considered a specific and sensitive target for dioxin toxicity

Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

International Nuclear Information System (INIS)

Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

1988-01-01

To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion

Adipose tissue macrophages impair preadipocyte differentiation in humans.

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Li Fen Liu

Full Text Available The physiologic mechanisms underlying the relationship between obesity and insulin resistance are not fully understood. Impaired adipocyte differentiation and localized inflammation characterize adipose tissue from obese, insulin-resistant humans. The directionality of this relationship is not known, however. The aim of the current study was to investigate whether adipose tissue inflammation is causally-related to impaired adipocyte differentiation.Abdominal subcutaneous(SAT and visceral(VAT adipose tissue was obtained from 20 human participants undergoing bariatric surgery. Preadipocytes were isolated, and cultured in the presence or absence of CD14+ macrophages obtained from the same adipose tissue sample. Adipocyte differentiation was quantified after 14 days via immunofluorescence, Oil-Red O, and adipogenic gene expression. Cytokine secretion by mature adipocytes cultured with or without CD14+macrophages was quantified.Adipocyte differentiation was significantly lower in VAT than SAT by all measures (p<0.001. With macrophage removal, SAT preadipocyte differentiation increased significantly as measured by immunofluorescence and gene expression, whereas VAT preadipocyte differentiation was unchanged. Adipocyte-secreted proinflammatory cytokines were higher and adiponectin lower in media from VAT vs SAT: macrophage removal reduced inflammatory cytokine and increased adiponectin secretion from both SAT and VAT adipocytes. Differentiation of preadipocytes from SAT but not VAT correlated inversely with systemic insulin resistance.The current results reveal that proinflammatory immune cells in human SAT are causally-related to impaired preadipocyte differentiation, which in turn is associated with systemic insulin resistance. In VAT, preadipocyte differentiation is poor even in the absence of tissue macrophages, pointing to inherent differences in fat storage potential between the two depots.

Direct and indirect links between parenting styles, self-concealment (secrets), impaired control over drinking and alcohol-related outcomes.

Science.gov (United States)

Hartman, Jessica D; Patock-Peckham, Julie A; Corbin, William R; Gates, Jonathan R; Leeman, Robert F; Luk, Jeremy W; King, Kevin M

2015-01-01

Self-concealment reflects uncomfortable feelings, thoughts, and information people have about themselves that they avoid telling others (Larson & Chastain, 1990). According to Larson and Chastain (1990) these secrets range from the slightly embarrassing to the very distressing with an individual's most traumatic experiences often concealed. Parental attitudes including those involving self-disclosure are thought to be expressed in their choice of parenting style (Brand, Hatzinger, Beck, & Holsboer-Trachsler, 2009). The specific aim of this investigation was to examine the direct and indirect influences of parenting styles on self-concealment, impaired control over drinking (i.e. the inability to stop drinking when intended), alcohol use (quantity/frequency), and alcohol-related problems. A structural equation model with 419 (223 men, 196 women) university students was examined. Two and three path mediated effects were examined with the bias corrected bootstrap technique in Mplus. Having an authoritarian mother was directly linked to more self-concealment, while having an authoritative father was directly linked to less self-concealment. Higher levels of mother authoritarianism were indirectly linked to both increased alcohol use and alcohol-related problems through more self-concealment and more impaired control over drinking. Moreover, higher levels of father authoritativeness were indirectly linked to less alcohol use and alcohol-related problems through less self-concealment and less impaired control over drinking. These findings suggest that parenting styles influence vulnerabilities such as self-concealment in the impaired control over the drinking pathway to alcohol use and alcohol-related problems. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional characterization of the protein C A267T mutation: evidence for impaired secretion due to defective intracellular transport

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Tjeldhorn Lena

2010-09-01

Full Text Available Abstract Background Activated protein C (PC is a serine protease that regulates blood coagulation by inactivating coagulation factors Va and VIIIa. PC deficiency is an autosomally inherited disorder associated with a high risk of recurrent venous thrombosis. The aim of the study was to explore the mechanisms responsible for severe PC deficiency in a patient with the protein C A267T mutation by in-vitro expression studies. Results Huh7 and CHO-K1 cells were transiently transfected with expression vectors containing wild-type (WT PC and mutated PC (A267T PC cDNAs. PC mRNA levels were assessed by qRT-PCR and the PC protein levels were measured by ELISA. The mRNA levels of WT PC and A267T PC were similar, while the intracellular protein level of A267T PC was moderately decreased compared to WT PC. The secretion of A267T PC into the medium was severely impaired. No differences in molecular weights were observed between WT and A267T PC before and after treatment with endo-β-N-acetylglucosaminidase. Proteasomal and lysosomal degradations were examined using lactacystin and bafilomycin, respectively, and revealed that A267T PC was slightly more susceptible for proteasomal degradation than WT PC. Intracellular co-localization analysis indicated that A267T PC was mainly located in the endoplasmic reticulum (ER, whereas WT PC was observed in both ER and Golgi. Conclusions In contrast to what has been reported for other PC mutants, intracellular degradation of A267T PC was not the main/dominant mechanism underlying the reduced intracellular and secretion levels of PC. Our results indicate that the A267T mutation most likely caused misfolding of PC, which might lead to increased retention of the mutated PC in ER.

Protection of business and industrial secrets under the Atomic Energy Act and the relevant ordinances governing licensing and supervisory procedures

International Nuclear Information System (INIS)

Steinberg, R.

1988-01-01

The article deals with problems concerning the protection of secret information in licensing and supervisory procedures under the Atomic Energy Act and the relevant ordinances. The extent of the secret protection of business and industrial secrets is regulated differently for both procedures. These legal provisions have to be interpreted with due consideration for third party interests in information. (WG) [de

Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

Science.gov (United States)

Branco, Renato Chaves Souto; Camargo, Rafael Ludemann; Batista, Thiago Martins; Vettorazzi, Jean Franciesco; Borck, Patrícia Cristine; Dos Santos-Silva, Junia Carolina Rebelo; Boschero, Antonio Carlos; Zoppi, Cláudio Cesar; Carneiro, Everardo Magalhães

2017-09-01

Taurine (Tau) restores β-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Afterward, mice received a high-fat diet (HFD) for 8 wk [CD + HFD (CH) and RD + HFD (RH)] with or without 5% Tau supplementation after weaning on their drinking water [CH + Tau (CHT) and RH + Tau (RHT)]. The HFD increased insulin secretion through mitochondrial metabolism in CH and RH. Tau prevented all those alterations in CHT only. The expression of the taurine transporter (Tau-T), as well as Tau content in pancreatic islets, was increased in CH but had no effect on RH. Protein malnutrition programs β cells and impairs Tau-induced restoration of mitochondrial metabolism and biogenesis. This may be associated with modulation of the expression of Tau-T in pancreatic islets, which may be responsible for the absence of effect of Tau in protein-malnourished obese mice.-Branco, R. C. S., Camargo, R. L., Batista, T. M., Vettorazzi, J. F., Borck, P. C., dos Santos-Silva, J. C. R., Boschero, A. C., Zoppi, C. C., Carneiro, E. M. Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion. © FASEB.

Binaural speech discrimination under noise in hearing-impaired listeners

Science.gov (United States)

Kumar, K. V.; Rao, A. B.

1988-01-01

This paper presents the results of an assessment of speech discrimination by hearing-impaired listeners (sensori-neural, conductive, and mixed groups) under binaural free-field listening in the presence of background noise. Subjects with pure-tone thresholds greater than 20 dB in 0.5, 1.0 and 2.0 kHz were presented with a version of the W-22 list of phonetically balanced words under three conditions: (1) 'quiet', with the chamber noise below 28 dB and speech at 60 dB; (2) at a constant S/N ratio of +10 dB, and with a background white noise at 70 dB; and (3) same as condition (2), but with the background noise at 80 dB. The mean speech discrimination scores decreased significantly with noise in all groups. However, the decrease in binaural speech discrimination scores with an increase in hearing impairment was less for material presented under the noise conditions than for the material presented in quiet.

Synaptotagmin-7 phosphorylation mediates GLP-1-dependent potentiation of insulin secretion from β-cells

DEFF Research Database (Denmark)

Wu, Bingbing; Wei, Shunhui; Petersen, Natalia

2015-01-01

Glucose stimulates insulin secretion from β-cells by increasing intracellular Ca(2+). Ca(2+) then binds to synaptotagmin-7 as a major Ca(2+) sensor for exocytosis, triggering secretory granule fusion and insulin secretion. In type-2 diabetes, insulin secretion is impaired; this impairment...... is ameliorated by glucagon-like peptide-1 (GLP-1) or by GLP-1 receptor agonists, which improve glucose homeostasis. However, the mechanism by which GLP-1 receptor agonists boost insulin secretion remains unclear. Here, we report that GLP-1 stimulates protein kinase A (PKA)-dependent phosphorylation...... of synaptotagmin-7 at serine-103, which enhances glucose- and Ca(2+)-stimulated insulin secretion and accounts for the improvement of glucose homeostasis by GLP-1. A phospho-mimetic synaptotagmin-7 mutant enhances Ca(2+)-triggered exocytosis, whereas a phospho-inactive synaptotagmin-7 mutant disrupts GLP-1...

Adrenocorticotropic Hormone Secreting Pheochromocytoma Underlying Glucocorticoid Induced Pheochromocytoma Crisis

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Gil A. Geva

2018-01-01

Full Text Available Context. Pheochromocytomas are hormone secreting tumors of the medulla of the adrenal glands found in 0.1–0.5% of patients with hypertension. The vast majority of pheochromocytomas secrete catecholamines, but they have been occasionally shown to also secrete interleukins, calcitonin, testosterone, and in rare cases adrenocorticotropic hormone. Pheochromocytoma crisis is a life threatening event in which high levels of catecholamines cause a systemic reaction leading to organ failure. Case Description. A 70-year-old man was admitted with acute myocardial ischemia following glucocorticoid administration as part of an endocrine workup for an adrenal mass. Cardiac catheterization disclosed patent coronary arteries and he was discharged. A year later he returned with similar angina-like chest pain. During hospitalization, he suffered additional events of chest pain, shortness of breath, and palpitations following administration of glucocorticoids as preparation for intravenous contrast administration. Throughout his admission, the patient demonstrated both signs of Cushing’s syndrome and high catecholamine levels. Following stabilization of vital parameters and serum electrolytes, the adrenal mass was resected surgically and was found to harbor an adrenocorticotropic hormone secreting pheochromocytoma. This is the first documented case of adrenocorticotropic hormone secreting pheochromocytoma complicated by glucocorticoid induced pheochromocytoma crisis. Conclusion. Care should be taken when administering high doses of glucocorticoids to patients with suspected pheochromocytoma, even in a patient with concomitant Cushing’s syndrome.

Physiology of bile secretion.

Science.gov (United States)

Esteller, Alejandro

2008-10-07

The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

Impaired decision-making under risk in individuals with alcohol dependence

Science.gov (United States)

Brevers, Damien; Bechara, Antoine; Cleeremans, Axel; Kornreich, Charles; Verbanck, Paul; Noël, Xavier

2014-01-01

Background Alcohol dependence is associated with poor decision-making under ambiguity, that is, when decisions are to be made in the absence of known probabilities of reward and loss. However, little is known regarding decisions made by individuals with alcohol dependence in the context of known probabilities (decision under risk). In this study, we investigated the relative contribution of these distinct aspects of decision making to alcohol dependence. Methods Thirty recently detoxified and sober asymptomatic alcohol-dependent individuals, and thirty healthy control participants were tested for decision-making under ambiguity (using the Iowa Gambling Task), and decision-making under-risk (using the Cups Task and Coin Flipping Task). We also tested their capacities for working memory storage (Digit-span Forward), and dual-tasking (Operation-span Task). Results Compared to healthy control participants, alcohol-dependent individuals made disadvantageous decisions on the Iowa Gambling Task, reflecting poor decisions under ambiguity. They also made more risky choices on the Cups and Coin Flipping Tasks reflecting poor decision-making under risk. In addition, alcohol-dependent participants showed some working memory impairments, as measured by the dual tasking, and the degree of this impairment correlated with high-risk decision-making, thus suggesting a relationship between processes sub-serving working memory and risky decisions. Conclusion These results suggest that alcohol dependent individuals are impaired in their ability to decide optimally in multiple facets of uncertainty (i.e., both risk and ambiguity), and that at least some aspects of these deficits are linked to poor working memory processes. PMID:24948198

Insulin secretion and action in North Indian women during pregnancy.

Science.gov (United States)

Arora, G P; Almgren, P; Thaman, R G; Pal, A; Groop, L; Vaag, A; Prasad, R B; Brøns, C

2017-10-01

The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1-h glucose value, in a high-risk Indian population from Punjab. Insulin secretion (HOMA2-B) and insulin action (HOMA2-IR) were assessed in 4665 Indian women with or without gestational diabetes defined by the GDM1999 or adapted GDM2013 criteria. Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were independently associated with increased insulin resistance. Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more severe impairments of insulin secretion and action. © 2017 Diabetes UK.

PREFERENTIAL SECRETION OF INDUCIBLE HSP70 BY VITILIGO MELANOCYTES UNDER STRESS

Science.gov (United States)

Mosenson, Jeffrey A.; Flood, Kelsey; Klarquist, Jared; Eby, Jonathan M.; Koshoffer, Amy; Boissy, Raymond E.; Overbeck, Andreas; C.Tung, Rebecca; Poole, I. Caroline Le

2014-01-01

SUMMARY Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes. PMID:24354861

Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion.

Science.gov (United States)

Wikner, J; Hirsch, U; Wetterberg, L; Röjdmark, S

1998-08-01

Most patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin)--affecting both sleep and pain perception--appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s-MT) level is also low in these patients. Eight patients with FMS and 8 healthy sex-, BMI-, and age-matched controls were included in the study. s-MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means. The FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300-0700 h (mean +/- SEM): 1.70 +/- 0.17 vs 2.48 +/- 0.38 nmol/l; P < 0.05). Also the s-MT peak value was significantly lower in the patient group: 0.28 +/- 0.03 vs 0.44 +/- 0.06 nmol/l; P < 0.05). Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.

Insulin-like growth factor-1 is a negative modulator of glucagon secretion

OpenAIRE

Mancuso, Elettra; Mannino, Gaia C.; Fatta, Concetta Di; Fuoco, Anastasia; Spiga, Rosangela; Andreozzi, Francesco; Sesti, Giorgio

2017-01-01

Glucagon secretion involves a combination of paracrine, autocrine, hormonal, and autonomic neural mechanisms. Type 2 diabetes often presents impaired glucagon suppression by insulin and glucose. Insulin-like growth factor-I (IGF-1) has elevated homology with insulin, and regulates pancreatic ?-cells insulin secretion. Insulin and IGF-1 receptors share considerable structure homology and function. We hypothesized the existence of a mechanism linking the inhibition of ?-cells glucagon secretion...

Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

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Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

2014-03-01

This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age.

Science.gov (United States)

Veldhuis, Johannes; Yang, Rebecca; Roelfsema, Ferdinand; Takahashi, Paul

2016-02-01

In the experimental animal, inflammatory signals quench LH's feedforward drive of testosterone (T) secretion and appear to impair GnRH-LH output. The degree to which such suppressive effects operate in the human is not known. To test the hypothesis that IL-2 impairs LH's feedforward drive on T and T's feedback inhibition of LH secretion in healthy men. Mayo Center for Translational Science Activities. A total of 35 healthy men, 17 young and 18 older. Randomized prospective double-blind saline-controlled study of IL-2 infusion in 2 doses with concurrent 10-minute blood sampling for 24 hours. Deconvolution analysis of LH and T secretion. After saline injection, older compared with young men exhibited reduced LH feedforward drive on T secretion (P enforces biochemical hypogonadism, viz, combined feedforward block and feedback amplification; and 2) unequal absolute inhibition of T and LH secretion by IL-2 in young and older men. These outcomes establish that the male gonadal axis is susceptible to dual-site suppression by a prototypic inflammatory mediator. Thus, we postulate that selected ILs might also enforce male hypogonadism in chronic systemic inflammation.

Salinity Alters the Polyisoprenoid Alcohol Content and Composition of Both Salt-Secreting and Non–Salt-Secreting Mangrove Seedlings

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Mohammad Basyuni

2017-10-01

Full Text Available The effects of salinity on the polyisoprenoid alcohol content and composition of the salt-secreting mangrove species Avicennia marina and Sonneratia alba and the non–salt-secreting species Bruguiera gymnorrhiza and Kandelia obovata were studied. The seedlings of mangroves were grown for 5 months under 0% and 3% salt concentrations. The occurrence, content, and distribution of four mangrove seedlings were analyzed by two-dimensional thin layer chromatography. The structural groups of the polyprenols and dolichols in the leaves and roots were classified into two types (I and II. In type I, dolichols predominated over polyprenols (more than 90%, whereas in type II, the occurrence of both polyprenols and dolichols was observed. Polyprenols were not detected in the leaves of A. marina and B. gymnorrhiza under 0% salt (control, but were detected in small amounts in K. obovata leaves; however, significant amounts were found in the 3% salinity group. This finding in A. marina, B. gymnorrhiza, and K. obovata leaves implies a change to the structural group: under 0% salt concentrations, the groups are classified as type I, but become type II under 3% salt concentrations. The occurrence of ficaprenol (C50–55 was found only in the leaves of the non–salt-secreting species B. gymnorrhiza and K. obovata under 3% salinity and not in the salt-secreting species A. marina or S. alba. It is noteworthy that the polyisoprenoid type in the roots of the four species showed no change under salinity; the two salt-secreting species A. marina and S. alba contained type I under 0% and 3% salt concentrations. On the other hand, type II polyisoprenoids were identified in the non–salt-secreting species B. gymnorrhiza and K. obovata under 0% and 3% salinity conditions. This finding suggested that polyisoprenoids play a protective role against salinity in the mangrove leaves of both salt-secreting and non–salt-secreting species.

Selective impairment of decision making under ambiguity in alexithymia.

Science.gov (United States)

Zhang, Lei; Wang, Xue; Zhu, Yu; Li, Hongchen; Zhu, Chunyan; Yu, Fengqiong; Wang, Kai

2017-11-28

Alexithymia is characterised by difficulties identifying and describing emotions. Few studies have investigated how alexithymia influences decision-making under different conditions (ambiguity and risk). This study aimed to examine whether alexithymia contributes to impairment in decision-making. This study included 42 participants with high scores in the Chinese version of Toronto Alexithymia Scale (alexithymia group), and 44 matched subjects with low scores (control group). Decision-making was measured using the Iowa Gambling Task (IGT) and the Game of Dice Task (GDT). The main findings of this study revealed selective deficits in IGT performance for the alexithymia group, while GDT performance was unimpaired when compared with the control group. In IGT, total netscores were lower for the alexithymia group compared to the control group, particularly with regard to block 5. Moreover, the alexithymia individuals selected significantly more adverse cards than the controls, indicating significant decision-making impairments. Alexithymia selectively influences decision-making under ambiguity.

Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

International Nuclear Information System (INIS)

Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El

2016-01-01

To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma

Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

2016-06-15

To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma.

Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age

Science.gov (United States)

Yang, Rebecca; Roelfsema, Ferdinand; Takahashi, Paul

2016-01-01

Context: In the experimental animal, inflammatory signals quench LH's feedforward drive of testosterone (T) secretion and appear to impair GnRH-LH output. The degree to which such suppressive effects operate in the human is not known. Objective: To test the hypothesis that IL-2 impairs LH's feedforward drive on T and T's feedback inhibition of LH secretion in healthy men. Setting: Mayo Center for Translational Science Activities. Patients or Other Participants: A total of 35 healthy men, 17 young and 18 older. Interventions: Randomized prospective double-blind saline-controlled study of IL-2 infusion in 2 doses with concurrent 10-minute blood sampling for 24 hours. Main Outcome Measures: Deconvolution analysis of LH and T secretion. Results: After saline injection, older compared with young men exhibited reduced LH feedforward drive on T secretion (P feedback inhibition of LH secretion (P feedforward onto T secretion declined markedly especially in young subjects (P feedback on LH secretion especially in older volunteers. Conclusion: This investigation confirms combined feedforward and feedback deficits in older relative to young men given saline and demonstrates 1) joint mechanisms by which IL-2 enforces biochemical hypogonadism, viz, combined feedforward block and feedback amplification; and 2) unequal absolute inhibition of T and LH secretion by IL-2 in young and older men. These outcomes establish that the male gonadal axis is susceptible to dual-site suppression by a prototypic inflammatory mediator. Thus, we postulate that selected ILs might also enforce male hypogonadism in chronic systemic inflammation. PMID:26600270

Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion.

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Michela Riz

2015-12-01

Full Text Available Intestinal L-cells sense glucose and other nutrients, and in response release glucagon-like peptide 1 (GLP-1, peptide YY and other hormones with anti-diabetic and weight-reducing effects. The stimulus-secretion pathway in L-cells is still poorly understood, although it is known that GLP-1 secreting cells use sodium-glucose co-transporters (SGLT and ATP-sensitive K+-channels (K(ATP-channels to sense intestinal glucose levels. Electrical activity then transduces glucose sensing to Ca2+-stimulated exocytosis. This particular glucose-sensing arrangement with glucose triggering both a depolarizing SGLT current as well as leading to closure of the hyperpolarizing K(ATP current is of more general interest for our understanding of glucose-sensing cells. To dissect the interactions of these two glucose-sensing mechanisms, we build a mathematical model of electrical activity underlying GLP-1 secretion. Two sets of model parameters are presented: one set represents primary mouse colonic L-cells; the other set is based on data from the GLP-1 secreting GLUTag cell line. The model is then used to obtain insight into the differences in glucose-sensing between primary L-cells and GLUTag cells. Our results illuminate how the two glucose-sensing mechanisms interact, and suggest that the depolarizing effect of SGLT currents is modulated by K(ATP-channel activity. Based on our simulations, we propose that primary L-cells encode the glucose signal as changes in action potential amplitude, whereas GLUTag cells rely mainly on frequency modulation. The model should be useful for further basic, pharmacological and theoretical investigations of the cellular signals underlying endogenous GLP-1 and peptide YY release.

Secretion and activation of the Serratia marcescens hemolysin by structurally defined ShlB mutants.

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Pramanik, Avijit; Könninger, Ulrich; Selvam, Arun; Braun, Volkmar

2014-05-01

The ShlA hemolysin of Serratia marcescens is secreted across the outer membrane by the ShlB protein; ShlB belongs to the two-partner secretion system (type Vb), a subfamily of the Omp85 outer membrane protein assembly and secretion superfamily. During secretion, ShlA is converted from an inactive non-hemolytic form into an active hemolytic form. The structure of ShlB is predicted to consist of the N-terminal α-helix H1, followed by the two polypeptide-transport-associated domains POTRA P1 and P2, and the β-barrel of 16 β-strands. H1 is inserted into the pore of the β-barrel in the outer membrane; P1 and P2 are located in the periplasm. To obtain insights into the secretion and activation of ShlA by ShlB, we isolated ShlB mutants impaired in secretion and/or activation. The triple H1 P1 P2 mutant did not secrete ShlA. The P1 and P2 deletion derivatives secreted reduced amounts of ShlA, of which P1 showed some hemolysis, whereas P2 was inactive. Deletion of loop 6 (L6), which is conserved among exporters of the Omp85 family, compromised activation but retained low secretion. Secretion-negative mutants generated by random mutagenesis were located in loop 6. The inactive secreted ShlA derivatives were complemented in vitro to active ShlA by an N-terminal ShlA fragment (ShlA242) secreted by ShlB. Deletion of H1 did not impair secretion of hemolytic ShlA. The study defines domains of ShlB which are important for ShlA secretion and activation. Copyright © 2013 Elsevier GmbH. All rights reserved.

Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

Science.gov (United States)

Houtz, Jessica; Borden, Philip; Ceasrine, Alexis; Minichiello, Liliana; Kuruvilla, Rejji

2016-11-07

Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets. Tissue-specific deletion of NGF or TrkA, or acute disruption of TrkA signaling, impairs glucose tolerance and insulin secretion in mice. We show that internalized TrkA receptors promote insulin granule exocytosis via F-actin reorganization. Furthermore, NGF treatment augments glucose-induced insulin secretion in human islets. These findings reveal a non-neuronal role for neurotrophins and identify a new regulatory pathway in insulin secretion that can be targeted to ameliorate β cell dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells.

Science.gov (United States)

Hachiya, Hiroyuki; Miura, Yoshikazu; Inoue, Ken-Ichi; Park, Kyung Hwa; Takeuchi, Masayoshi; Kubota, Keiichi

2014-02-01

Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion. Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1 mg/ml bovine serum albumin (BSA) or 0.1 mg/ml Glu-AGE or Glycer-AGE-albumin. After 48 h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments [corrected]. Also, mRNA expression of genes associated with insulin secretion was measured. Insulin secretion induced by a high glucose concentration was 164.1 ± 6.0, 124.4 ± 4.4 (P < 0.05) and 119.8 ± 7.1 (P < 0.05) μU/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and α-ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle. Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Secretion management in the mechanically ventilated patient.

Science.gov (United States)

Branson, Richard D

2007-10-01

to improve secretion removal. Intrapulmonary percussive ventilation combines percussion with hyperinflation and a simulated cough, but the evidence for intrapulmonary percussive ventilation in mechanically ventilated patients is insufficient to support routine use. Secretion management in the mechanically ventilated patient consists of appropriate humidification and as-needed airway suctioning. Intermittent techniques may play a role when secretion retention persists despite adequate humidification and suctioning. The technique selected should remedy the suspected etiology of the secretion retention (eg, insufflation-exsufflation for impaired cough). Further research into secretion management in the mechanically ventilated patient is needed.

Gastric secretion elicited by conditioning in rats.

Science.gov (United States)

Caboclo, José Liberato Ferreira; Cury, Francico de Assis; Borin, Aldenis Albanese; Caboclo, Luís Otávio Sales Ferreira; Ribeiro, Maria Fernanda Sales Caboclo; de Freitas, Pedro José; Andersson, Sven

2009-01-01

To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

Science.gov (United States)

Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

2016-12-01

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

High-fat diet with stress impaired islets' insulin secretion by reducing plasma estradiol and pancreatic GLUT2 protein levels in rats' proestrus phase.

Science.gov (United States)

Salimi, M; Zardooz, H; Khodagholi, F; Rostamkhani, F; Shaerzadeh, F

2016-10-01

This study was conducted to determine whether two estrus phases (proestrus and diestrus) in female rats may influence the metabolic response to a high-fat diet and/or stress, focusing on pancreatic insulin secretion and content. Animals were divided into high-fat and normal diet groups, then each group was subdivided into stress and non-stress groups, and finally, each one of these was divided into proestrus and diestrus subgroups. At the end of high-fat diet treatment, foot-shock stress was applied to the animals. Then, blood samples were taken to measure plasma factors. Finally, the pancreas was removed for determination of glucose transporter 2 (GLUT2) protein levels and assessment of insulin content and secretion of the isolated islets. In the normal and high-fat diet groups, stress increased plasma corticosterone concentration in both phases. In both study phases, high-fat diet consumption decreased estradiol and increased leptin plasma levels. In the high-fat diet group in response to high glucose concentration, a reduction in insulin secretion was observed in the proestrus phase compared with the same phase in the normal diet group in the presence and absence of stress. Also, high-fat diet decreased the insulin content of islets in the proestrus phase compared with the normal diet. High-fat diet and/or stress caused a reduction in islet GLUT2 protein levels in both phases. In conclusion, it seems possible that high-fat diet alone or combined with foot-shock, predispose female rats to impaired insulin secretion, at least in part, by interfering with estradiol levels in the proestrus phase and decreasing pancreatic GLUT2 protein levels.

An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion

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Kyle S. McCommis

2016-08-01

Full Text Available Objective: Transport of pyruvate into the mitochondrial matrix by the Mitochondrial Pyruvate Carrier (MPC is an important and rate-limiting step in its metabolism. In pancreatic β-cells, mitochondrial pyruvate metabolism is thought to be important for glucose sensing and glucose-stimulated insulin secretion. Methods: To evaluate the role that the MPC plays in maintaining systemic glucose homeostasis, we used genetically-engineered Drosophila and mice with loss of MPC activity in insulin-producing cells. Results: In both species, MPC deficiency results in elevated blood sugar concentrations and glucose intolerance accompanied by impaired glucose-stimulated insulin secretion. In mouse islets, β-cell MPC-deficiency resulted in decreased respiration with glucose, ATP-sensitive potassium (KATP channel hyperactivity, and impaired insulin release. Moreover, treatment of pancreas-specific MPC knockout mice with glibenclamide, a sulfonylurea KATP channel inhibitor, improved defects in islet insulin secretion and abnormalities in glucose homeostasis in vivo. Finally, using a recently-developed biosensor for MPC activity, we show that the MPC is rapidly stimulated by glucose treatment in INS-1 insulinoma cells suggesting that glucose sensing is coupled to mitochondrial pyruvate carrier activity. Conclusions: Altogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia. Keywords: Stimulus-coupled secretion, Insulin, β-Cell, Diabetes, Pyruvate, Mitochondria, Drosophila

Impairment of T-regulatory cells in cord blood of atopic mothers.

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Schaub, Bianca; Liu, Jing; Höppler, Sabine; Haug, Severine; Sattler, Christine; Lluis, Anna; Illi, Sabina; von Mutius, Erika

2008-06-01

Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation. We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers. Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion. Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+)high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion. In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.

Phosphate starvation triggers production and secretion of an extracellular lipoprotein in Caulobacter crescentus.

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Sophie Le Blastier

Full Text Available Life in oligotrophic environments necessitates quick adaptive responses to a sudden lack of nutrients. Secretion of specific degradative enzymes into the extracellular medium is a means to mobilize the required nutrient from nearby sources. The aquatic bacterium Caulobacter crescentus must often face changes in its environment such as phosphate limitation. Evidence reported in this paper indicates that under phosphate starvation, C. crescentus produces a membrane surface-anchored lipoprotein named ElpS subsequently released into the extracellular medium. A complete set of 12 genes encoding a type II secretion system (T2SS is located adjacent to the elpS locus in the C. crescentus genome. Deletion of this T2SS impairs release of ElpS in the environment, which surprisingly remains present at the cell surface, indicating that the T2SS is not involved in the translocation of ElpS to the outer membrane but rather in its release. Accordingly, treatment with protease inhibitors prevents release of ElpS in the extracellular medium suggesting that ElpS secretion relies on a T2SS-secreted protease. Finally, secretion of ElpS is associated with an increase in alkaline phosphatase activity in culture supernatants, suggesting a role of the secreted protein in inorganic phosphate mobilization. In conclusion, we have shown that upon phosphate starvation, C. crescentus produces an outer membrane bound lipoprotein, ElpS, which is further cleaved and released in the extracellular medium in a T2SS-dependent manner. Our data suggest that ElpS is associated with an alkaline phosphatase activity, thereby allowing the bacterium to gather inorganic phosphates from a poor environment.

Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion

DEFF Research Database (Denmark)

Lyssenko, Valeriya; Nagorny, Cecilia L F; Erdos, Michael R

2009-01-01

Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype...... was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets....... Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which...

In vitro secretion of TNF-α from bone marrow mononuclear cells incubated on amino group modified TiO2 nano-composite under ultrasound irradiation

International Nuclear Information System (INIS)

Furuzono, T.; Masuda, M.; Nitta, N.; Kaya, A.; Yamane, T.; Okada, M.

2010-01-01

It is recently known that titanium dioxide (TiO 2 ) can be excited by ultrasound and release of OH radicals on the surface. In this study, secretion of an indirect angiogenic factor, tumor necrosis factor-α (TNF-α), from bone marrow mononuclear cells (BM-MNC) incubated on amino group modified TiO 2 nano-particles covalently coated on polyester fabric (TiO 2 /PET) under ultrasonic irradiation was examined in vitro. The cell viability and TNF-α secretion were measured under ultrasound irradiation condition with 255 mW/cm 2 of intensity, which is below the highest output (1 W/cm 2 ) specified in the safety standard for a medical ultrasonic diagnostic apparatus. The living cell number on the TiO 2 /PET and original PET with/without continuous ultrasound irradiation was unchanged statistically by ANOVA test. TNF-α secretion level from BM-MNC remarkably increased on the TiO 2 /PET under ultrasonic irradiation without cell damage. It was, therefore, thought that the high level of TNF-α secretion on the TiO 2 nano-composite by ultrasound irradiation was due to oxidative stress induced from OH radicals on TiO 2 .

Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

Energy Technology Data Exchange (ETDEWEB)

Yu, Yunli, E-mail: chrisyu1255@yahoo.com.cn [Department of Pharmaceutics, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Wang, Xinting, E-mail: wxinting1986@yahoo.com.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Can, E-mail: ltsan@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Yao, Dan, E-mail: erinyao@126.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Shanghai Institute of Materia Medica, Shanghai 201203 (China); Hu, Mengyue, E-mail: juliahmy@126.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia, E-mail: ljbzd@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Hu, Nan, E-mail: hn_324@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Li, E-mail: liulee@cpu.edu.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Xiaodong, E-mail: xdliu@cpu.edu.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)

2013-02-01

Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-day gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K{sub ATP} channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. -- Highlights: ► Gatifloxacin induced hyperglycemia both in diabetic rats and normal rats. ► Gatifloxacin enhanced GLP-1 secretion but inhibited insulin secretion in rats. ► Long-term exposure to high GLP-1 inhibited insulin secretion and biosynthesis. ► GLP-1 over-secretion may be

Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

International Nuclear Information System (INIS)

Yu, Yunli; Wang, Xinting; Liu, Can; Yao, Dan; Hu, Mengyue; Li, Jia; Hu, Nan; Liu, Li; Liu, Xiaodong

2013-01-01

Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-day gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K ATP channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. -- Highlights: ► Gatifloxacin induced hyperglycemia both in diabetic rats and normal rats. ► Gatifloxacin enhanced GLP-1 secretion but inhibited insulin secretion in rats. ► Long-term exposure to high GLP-1 inhibited insulin secretion and biosynthesis. ► GLP-1 over-secretion may be involved in

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

Energy Technology Data Exchange (ETDEWEB)

Lee, Je Min, E-mail: jemin@knu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of); Department of Horticultural Science, Kyungpook National University, Daegu (Korea, Republic of); Lee, Sang-Jik [Biotechnology Institute, Nongwoo Bio Co, Ltd, Yeoju (Korea, Republic of); Department of Plant Biology, Cornell University, Ithaca, NY (United States); Rose, Jocelyn K.C. [Department of Plant Biology, Cornell University, Ithaca, NY (United States); Yeam, Inhwa [Department of Horticulture and Breeding, Andong National University, Andong (Korea, Republic of); Kim, Byung-Dong [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of)

2014-04-18

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

International Nuclear Information System (INIS)

Lee, Je Min; Lee, Sang-Jik; Rose, Jocelyn K.C.; Yeam, Inhwa; Kim, Byung-Dong

2014-01-01

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening

Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1

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XingChun Wang

2015-01-01

Full Text Available The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels.

Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients

DEFF Research Database (Denmark)

Yabe, Daisuke; Kuroe, Akira; Watanabe, Koin

2015-01-01

AIMS: Hypersecretion of glucagon and reduced insulin secretion both contribute to hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of impaired glucagon and insulin secretions in glucose excursions at the various stages of T2DM development remain to be determined. METHODS...... secretions but not incretin secretion are involved in hyperglycemia after ingestion of nutrients in T2DM of even a short duration....

The cardiokine story unfolds: ischemic stress-induced protein secretion in the heart.

Science.gov (United States)

Doroudgar, Shirin; Glembotski, Christopher C

2011-04-01

Intercellular communication depends on many factors, including proteins released via the classical or non-classical secretory pathways, many of which must be properly folded to be functional. Owing to their adverse effects on the secretion machinery, stresses such as ischemia can impair the folding of secreted proteins. Paradoxically, cells rely on secreted proteins to mount a response designed to resist stress-induced damage. This review examines this paradox using proteins secreted from the heart, cardiokines, as examples, and focuses on how the ischemic heart maintains or even increases the release of select cardiokines that regulate important cellular processes in the heart, including excitation-contraction coupling, hypertrophic growth, myocardial remodeling and stem cell function, in ways that moderate ischemic damage and enhance cardiac repair. Copyright © 2010 Elsevier Ltd. All rights reserved.

Post-translational inhibition of IP-10 secretion in IEC by probiotic bacteria: impact on chronic inflammation.

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Gabriele Hoermannsperger

Full Text Available BACKGROUND: Clinical and experimental studies suggest that the probiotic mixture VSL#3 has protective activities in the context of inflammatory bowel disease (IBD. The aim of the study was to reveal bacterial strain-specific molecular mechanisms underlying the anti-inflammatory potential of VSL#3 in intestinal epithelial cells (IEC. METHODOLOGY/PRINCIPAL FINDINGS: VSL#3 inhibited TNF-induced secretion of the T-cell chemokine interferon-inducible protein (IP-10 in Mode-K cells. Lactobacillus casei (L. casei cell surface proteins were identified as active anti-inflammatory components of VSL#3. Interestingly, L. casei failed to block TNF-induced IP-10 promoter activity or IP-10 gene transcription at the mRNA expression level but completely inhibited IP-10 protein secretion as well as IP-10-mediated T-cell transmigration. Kinetic studies, pulse-chase experiments and the use of a pharmacological inhibitor for the export machinery (brefeldin A showed that L. casei did not impair initial IP-10 production but decreased intracellular IP-10 protein stability as a result of blocked IP-10 secretion. Although L. casei induced IP-10 ubiquitination, the inhibition of proteasomal or lysosomal degradation did not prevent the loss of intracellular IP-10. Most important for the mechanistic understanding, the inhibition of vesicular trafficking by 3-methyladenine (3-MA inhibited IP-10 but not IL-6 expression, mimicking the inhibitory effects of L. casei. These findings suggest that L. casei impairs vesicular pathways important for the secretion of IP-10, followed by subsequent degradation of the proinflammatory chemokine. Feeding studies in TNF(DeltaARE and IL-10(-/- mice revealed a compartimentalized protection of VSL#3 on the development of cecal but not on ileal or colonic inflammation. Consistent with reduced tissue pathology in IL-10(-/- mice, IP-10 protein expression was reduced in primary epithelial cells. CONCLUSIONS/SIGNIFICANCE: We demonstrate segment

Insulin secretion and action in North Indian women during pregnancy

DEFF Research Database (Denmark)

Arora, G P; Almgren, P; Thaman, R G

2017-01-01

. RESULTS: Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women......AIM: The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999...... independently associated with increased insulin resistance. CONCLUSIONS: Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more...

Molecular Mechanisms of Insulin Secretion and Insulin Action.

Science.gov (United States)

Flatt, Peter R.; Bailey, Clifford J.

1991-01-01

Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

Glucagon-like peptide-1 secretion in women with gestational diabetes mellitus during and after pregnancy.

Science.gov (United States)

Lencioni, C; Resi, V; Romero, F; Lupi, R; Volpe, L; Bertolotto, A; Ghio, A; Del Prato, S; Marchetti, P; Di Cianni, G

2011-10-01

Gestational diabetes mellitus (GDM) predisposes women to future development of Type 2 diabetes mellitus (DM2) and the two conditions share similar metabolic alterations. Recent observations suggest that a defective glucose stimulated insulin secretion by glucagon-like peptide-1 (GLP- 1) plays a role in the pathogenesis of DM2. Whether such a defect is impaired in GDM remains to be ascertained. We have determined GLP-1 secretion in response to oral glucose tolerance test (OGTT) in GDM and normal glucose tolerance (NGT) during and after pregnancy. 100-g-3h OGTT was performed in 12 GDM and 16 NGT women at 27.3 ± 4.1 weeks of gestation, for determination of plasma GLP-1, glucose, insulin, and C-peptide. Insulin sensitivity (ISI) and insulin secretion (first and second phase); as well as ISI-secretion index (ISSI) were also derived. NGT and GDM women were comparable for age pre-pregnancy body mass index (BMI) and weight gain. GDM had higher glucose area under the curve (AUC): 27,575.5 ± 3448 vs 20,685.88 ± 2715 mg/dl min (pwomen (2542 ± 273 vs 10,092 ± 7367 pmol·l-1·min-1, pwomen is inadequate for the prevailing glycemic levels both in pregnancy and post partum. Moreover, we cannot exclude that other important aspects of the incretin effect may be involved in GDM development.

Increased VLDL-triglyceride secretion precedes impaired control of endogenous glucose production in obese, normoglycemic men.

Science.gov (United States)

Sørensen, Lars P; Søndergaard, Esben; Nellemann, Birgitte; Christiansen, Jens S; Gormsen, Lars C; Nielsen, Søren

2011-09-01

To assess basal and insulin-mediated VLDL-triglyceride (TG) kinetics and the relationship between VLDL-TG secretion and hepatic insulin resistance assessed by endogenous glucose production (EGP) in obese and lean men. A total of 12 normoglycemic, obese (waist-to-hip ratio >0.9, BMI >30 kg/m(2)) and 12 lean (BMI 20-25 kg/m(2)) age-matched men were included. Ex vivo-labeled [1-(14)C]VLDL-TGs and [3-(3)H]glucose were infused postabsorptively and during a hyperinsulinemic-euglycemic clamp to determine VLDL-TG kinetics and EGP. Body composition was determined by dual X-ray absorptiometry and computed tomography scanning. Energy expenditure and substrate oxidation rates were measured by indirect calorimetry. Basal VLDL-TG secretion rates were increased in obese compared with lean men (1.25 ± 0.34 vs. 0.86 ± 0.34 μmol/kg fat-free mass [FFM]/min; P = 0.011), whereas there was no difference in clearance rates (150 ± 56 vs. 162 ± 77 mL/min; P = NS), resulting in greater VLDL-TG concentrations (0.74 ± 0.40 vs. 0.38 ± 0.20 mmol/L; P = 0.011). The absolute insulin-mediated suppression of VLDL-TG secretion was similar in the groups. However, the percentage reduction (-36 ± 18 vs. -54 ± 10%; P = 0.008) and achieved VLDL-TG secretion rates (0.76 ± 0.20 vs. 0.41 ± 0.19 μmol/kg FFM/min; P lean men (-17 ± 18 vs. 7 ± 20%; P = 0.007), resulting in less percentage reduction of VLDL-TG concentrations in obese men (-22 ± 20 vs. -56 ± 11%; P < 0.001). Insulin-suppressed EGP was similar (0.4 [0.0-0.8] vs. 0.1 [0.0-1.2] mg/kg FFM/min (median [range]); P = NS), and the percentage reduction was equivalent (-80% [57-98] vs. -98% [49-100], P = NS). Insulin-mediated glucose disposal was significantly reduced in obese men. Basal VLDL-TG secretion rates are increased in normoglycemic but insulin-resistant, obese men, resulting in hypertriglyceridemia. Insulin-mediated suppression of EGP is preserved in obese men, whereas suppression of VLDL-TG secretion is less pronounced in obese

DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet

Directory of Open Access Journals (Sweden)

Katherine Veras

2014-01-01

Full Text Available Dehydroepiandrosterone (DHEA and the dehydroepiandrosterone sulfate (DHEA-S are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

Changes in somatotropic hormone secretion in patients with acute myocardial infarct

International Nuclear Information System (INIS)

Milanov, S.; Milkov, V.; Atanasov, I.; Sotirov, I.; Kamenova, Ts.

1982-01-01

Secretion of somatotropic hormone (STH) was estimated by radioimmunoassay during intravenous glucose-tolerance test (IGTT) in 17 patients with acute myocardial infarct (AMI) and 10 patients with chronic ischemic heart disease, without evidence of recent myocardial infarct. In both groups of patients the basal STH levels were elevated, as compared to those in normal individuals, with statistical significance (p<0.001). During the IGTT, somatotropic hormone in AMI patients was slightly reduced, which was out of proportion to the blood glucose changes. During IGTT in patients with chronic ischemic heart disease, the somatotropic hormone secretion, though increased, followed the blood glucose changes. These changes in STH secretion during IGTT in AMI patients are indicative of impaired hypothalamo-pituitary interrelations mediated by central nervous route. (author)

Trade Secrets in Life Science and Pharmaceutical Companies

Science.gov (United States)

Nealey, Tara; Daignault, Ronald M.; Cai, Yu

2015-01-01

Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through “improper means” is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today’s interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees’ careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. PMID:25414378

Trade secrets in life science and pharmaceutical companies.

Science.gov (United States)

Nealey, Tara; Daignault, Ronald M; Cai, Yu

2014-11-20

Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through "improper means" is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today's interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees' careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

Directory of Open Access Journals (Sweden)

Jianhui Liu

Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

Will They or Won't They? Secret Telling in Interpersonal Interactions.

Science.gov (United States)

Kowalski, Robin Marie; Morgan, Chad Alan; Whittaker, Elizabeth; Zaremba, Brittany; Frazee, Laura; Dean, Jessica

2015-01-01

This study investigated predictors of within-gender secret telling. Eighty-eight participants were exposed to either a "positive" or a "negative" secret about another individual. Just under 20% of participants told the secret. Conscientiousness, secret condition, empathy, and the conscientiousness by secret condition interaction had effects on the rate of secret telling, χ(2) (5,82) = 17.78, p = .003, AIC = 80.60. Conscientiousness had a negative effect on secret telling among participants that told the "negative" secret.

Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?

DEFF Research Database (Denmark)

Faerch, K; Borch-Johnsen, K; Holst, Jens Juul

2009-01-01

Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology and pathophysiology of the prediabetic states...... might give a basis for the development of individualised prevention and treatment strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the development of the different prediabetic states. The pathophysiology of i-IFG seems to include...... the following key defects: reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised by reduced peripheral insulin...

Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

Science.gov (United States)

Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

2016-11-01

Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reactive oxygen species as a signal in glucose-stimulated insulin secretion.

Science.gov (United States)

Pi, Jingbo; Bai, Yushi; Zhang, Qiang; Wong, Victoria; Floering, Lisa M; Daniel, Kiefer; Reece, Jeffrey M; Deeney, Jude T; Andersen, Melvin E; Corkey, Barbara E; Collins, Sheila

2007-07-01

One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.

In vitro secretion of TNF-{alpha} from bone marrow mononuclear cells incubated on amino group modified TiO{sub 2} nano-composite under ultrasound irradiation

Energy Technology Data Exchange (ETDEWEB)

Furuzono, T., E-mail: furuzono@ri.ncvc.go.jp [Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 (Japan); Masuda, M. [Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 (Japan); Nitta, N.; Kaya, A.; Yamane, T. [Institute for Human Science and Biomedical Engineering, National Institute of Advanced Industrial Science and Technology, 1-2-1 Namiki, Tsukuba, Ibaraki, 305-8564 (Japan); Okada, M. [Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 (Japan)

2010-10-15

It is recently known that titanium dioxide (TiO{sub 2}) can be excited by ultrasound and release of OH radicals on the surface. In this study, secretion of an indirect angiogenic factor, tumor necrosis factor-{alpha} (TNF-{alpha}), from bone marrow mononuclear cells (BM-MNC) incubated on amino group modified TiO{sub 2} nano-particles covalently coated on polyester fabric (TiO{sub 2}/PET) under ultrasonic irradiation was examined in vitro. The cell viability and TNF-{alpha} secretion were measured under ultrasound irradiation condition with 255 mW/cm{sup 2} of intensity, which is below the highest output (1 W/cm{sup 2}) specified in the safety standard for a medical ultrasonic diagnostic apparatus. The living cell number on the TiO{sub 2}/PET and original PET with/without continuous ultrasound irradiation was unchanged statistically by ANOVA test. TNF-{alpha} secretion level from BM-MNC remarkably increased on the TiO{sub 2}/PET under ultrasonic irradiation without cell damage. It was, therefore, thought that the high level of TNF-{alpha} secretion on the TiO{sub 2} nano-composite by ultrasound irradiation was due to oxidative stress induced from OH radicals on TiO{sub 2}.

EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

Directory of Open Access Journals (Sweden)

Ya. S. Onokhina

2013-01-01

Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

Science.gov (United States)

Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

2015-04-01

The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

Science.gov (United States)

Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

2015-01-01

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

Investment in secreted enzymes during nutrient-limited growth is utility dependent.

Science.gov (United States)

Cezairliyan, Brent; Ausubel, Frederick M

2017-09-12

Pathogenic bacteria secrete toxins and degradative enzymes that facilitate their growth by liberating nutrients from the environment. To understand bacterial growth under nutrient-limited conditions, we studied resource allocation between cellular and secreted components by the pathogenic bacterium Pseudomonas aeruginosa during growth on a protein substrate that requires extracellular digestion by secreted proteases. We identified a quantitative relationship between the rate of increase of cellular biomass under nutrient-limiting growth conditions and the rate of increase in investment in secreted proteases. Production of secreted proteases is stimulated by secreted signals that convey information about the utility of secreted proteins during nutrient-limited growth. Growth modeling using this relationship recapitulated the observed kinetics of bacterial growth on a protein substrate. The proposed regulatory strategy suggests a rationale for quorum-sensing-dependent stimulation of the production of secreted enzymes whereby investment in secreted enzymes occurs in proportion to the utility they confer. Our model provides a framework that can be applied toward understanding bacterial growth in many environments where growth rate is limited by the availability of nutrients.

Effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells

International Nuclear Information System (INIS)

Hochberg, Z.; Kuten, A.; Hertz, P.; Tatcher, M.; Kedar, A.; Benderly, A.

1983-01-01

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100 to 1500 rad. Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0 to 300 rad, followed by a decline between 300 to 750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad

Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

International Nuclear Information System (INIS)

Sorrell, M.F.; Nauss, J.M.; Donohue, T.M. Jr.; Tuma, D.J.

1983-01-01

The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [ 14 C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [ 14 C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [ 14 C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration

A case of spontaneous hypoglycaemia and impaired glucose tolerance in the same patient.

LENUS (Irish Health Repository)

Thabit, Hood

2012-01-31

We present a rare case of an insulin-like growth factor-2 (IGF-2)-secreting tumour of the thorax. This patient demonstrated the combination of fasting hypoglycaemia and impaired glucose tolerance on oral glucose tolerance testing, which has not been previously described in this condition. A review of the literature of IGF-2-secreting intrathoracic tumours is presented here.

Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system

Directory of Open Access Journals (Sweden)

Singsuksawat Ekapot

2010-06-01

Full Text Available Abstract Background Burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the Northeast of Thailand, where saline soil and water are prevalent. Moreover, recent reports indicate a potential pathogenic role for B. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (NaCl concentration in airway surface liquid has been proposed. These observations raise the possibility that high salinity may represent a favorable niche for B. pseudomallei. We therefore investigated the global transcriptional response of B. pseudomallei to increased salinity using microarray analysis. Results Transcriptome analysis of B. pseudomallei under salt stress revealed several genes significantly up-regulated in the presence of 320 mM NaCl including genes associated with the bsa-derived Type III secretion system (T3SS. Microarray data were verified by reverse transcriptase-polymerase chain reactions (RT-PCR. Western blot analysis confirmed the increased expression and secretion of the invasion-associated type III secreted proteins BipD and BopE in B. pseudomallei cultures at 170 and 320 mM NaCl relative to salt-free medium. Furthermore, salt-treated B. pseudomallei exhibited greater invasion efficiency into the lung epithelial cell line A549 in a manner partly dependent on a functional Bsa system. Conclusions B. pseudomallei responds to salt stress by modulating the transcription of a relatively small set of genes, among which is the bsa locus associated with invasion and virulence. Expression and secretion of Bsa-secreted proteins was elevated in the presence of exogenous salt and the invasion efficiency was enhanced. Our data indicate that salinity has the potential to influence the virulence of B. pseudomallei.

Impaired CD23 and CD62L expression and tissue inhibitors of metalloproteinases secretion by eosinophils in adults with atopic dermatitis.

Science.gov (United States)

de Oliveira Titz, T; Orfali, R L; de Lollo, C; Dos Santos, V G; da Silva Duarte, A J; Sato, M N; Aoki, V

2016-12-01

Eosinophils are multifunctional, polymorphonuclear leucocytes that secrete proteins within cytoplasmic granules, such as cytokines, chemokines, metalloproteinases (MMPs) and metalloproteinases tissue inhibitors (TIMPs). Although eosinophilia is a hallmark of atopic dermatitis (AD), several functional aspects of eosinophils remain unknown. We aimed to evaluate the phenotype and functional response of eosinophils under staphylococcal enterotoxin B (SEB) and Toll-like receptor (TLR)-2/6 (FSL-1) stimulation in the secretion of CCL5, MMPs and TIMPs in adults with AD. Forty-one adult patients with AD and 45 healthy controls enrolled for the study. Phenotype of eosinophils from granulocytes of peripheral blood was analysed by flow cytometry. We performed evaluation of CCL5 (cytometric bead array), MMP and TIMP (ELISA) secretion, in culture supernatants of purified eosinophils stimulated with SEB or TLR2/6 agonist (FSL-1). We found a higher frequency of LIN1 - CCR3 + eosinophils, and decreased expression of CD23 and CD62L receptors in eosinophils of AD patients. There was no difference in MMP and TIMP serum levels between the evaluated groups. However, we detected decreased basal levels of TIMP-1, TIMP-2 and CCL5 in culture supernatants from purified, unstimulated eosinophils from AD patients. In adults with AD, phenotypical features of eosinophils reveal decreased expression of early activation and L-selectin receptors. Regarding the functional profile of purified eosinophils related to tissue remodelling in atopic dermatitis, innate immune stimulation (TLR2/6 agonist and SEB) did not affect the ratio of MMP/TIMPs secretion in AD. Our findings reinforce the potential breakdown in tissue remodelling process mediated by eosinophils in AD. © 2016 European Academy of Dermatology and Venereology.

Pre-schoolers suffering from psychiatric disorders show increased cortisol secretion and poor sleep compared to healthy controls.

Science.gov (United States)

Hatzinger, Martin; Brand, Serge; Perren, Sonja; von Wyl, Anges; Stadelmann, Stephanie; von Klitzing, Kai; Holsboer-Trachsler, Edith

2012-05-01

Various studies of child cortisol secretion and sleep show a close association between poor sleep, deterioration of the HPA axis and unfavorable psychological functioning. However, there is little evidence as to whether these associations are clearly present in pre-school children suffering from psychiatric disorders. A total of 30 pre-schoolers suffering from psychiatric disorders (anxiety, adjustment disorders, emotional and attachment disorder; hyperactivity or oppositional disorder) and 35 healthy controls took part in the study. Saliva cortisol secretion was assessed both at baseline and under challenge conditions. Sleep was assessed via activity monitoring for seven consecutive days and nights, using a digital movement-measuring instrument. Parents and teachers completed questionnaires assessing children's cognitive, emotional and social functioning. The Berkeley Puppet Interview provided child-based reports of cognitive-emotional processes. Compared to healthy controls, children suffering from psychiatric disorders had much higher cortisol secretion both at baseline and under challenge conditions. Sleep was also more disturbed, and parents and teachers rated children suffering from psychiatric disorders as cognitively, emotionally and behaviorally more impaired, relative to healthy controls. Children with psychiatric disorders reported being more bullied and victimized. In five-year old children the presence of psychiatric disorders is reflected not only at psychological, social and behavioral, but also at neuroendocrine and sleep-related levels. It is likely that these children remain at increased risk for suffering from psychiatric difficulties later in life. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of menadione, a reactive oxygen generator, on leukotriene secretion from RBL-2H3 cells.

Science.gov (United States)

Kawamura, Fumio; Nakanishi, Mamoru; Hirashima, Naohide

2010-01-01

Reactive oxygen species (ROS) are produced in various cells and affect many biological processes. We previously reported that 2-methyl-1,4-naphtoquinone (menadione) inhibited Ca(2+) influx from the extracellular medium and exocytosis evoked by antigen stimulation in the mast cell line, RBL-2H3. Mast cells release various inflammatory mediators such as leukotrienes (LTs) and cytokines in addition to the exocytotic secretion of histamine. In this study, we investigated the effects of menadione on LT release in RBL-2H3. Treatment of RBL cells with menadione inhibited LTC(4) secretion induced by antigen stimulation. To elucidate the mechanism of this inhibition, we examined the effects of menadione on the activation process of 5-lipoxygenase that is responsible for the synthesis of LTs from arachidonic acid. Menadione did not affect the phosophorylation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, which regulates phosphorylation of 5-lipoxygenase. However, menadione inhibited the translocation of 5-lipoxygenase from the cytoplasm to the nuclear membrane. Together with the result that LT secretion was severely impaired in the absence of extracellular Ca2(2+), it is suggested that ROS produced by menadione inhibited LT secretion through impaired Ca2(2+) influx and 5-lipoxygenase translocation to the nuclear membrane.

Secretion of Flavins by Three Species of Methanotrophic Bacteria▿ †

OpenAIRE

Balasubramanian, Ramakrishnan; Levinson, Benjamin T.; Rosenzweig, Amy C.

2010-01-01

We detected flavins in the growth medium of the methanotrophic bacterium Methylocystis species strain M. Flavin secretion correlates with growth stage and increases under iron starvation conditions. Two other methanotrophs, Methylosinus trichosporium OB3b and Methylococcus capsulatus (Bath), secrete flavins, suggesting that flavin secretion may be common to many methanotrophic bacteria.

Decision making under explicit risk is impaired in individuals with human immunodeficiency virus (HIV).

Science.gov (United States)

Fujiwara, Esther; Tomlinson, Sara E; Purdon, Scot E; Gill, M John; Power, Christopher

2015-01-01

Human immunodeficiency virus (HIV) can affect the frontal-striatal brain regions, which are known to subserve decision-making functions. Previous studies have reported impaired decision making among HIV+ individuals using the Iowa Gambling Task, a task that assesses decision making under ambiguity. Previous study populations often had significant comorbidities such as past or present substance use disorders and/or hepatitis C virus coinfection, complicating conclusions about the unique contributions of HIV-infection to decision making. Decision making under explicit risk has very rarely been examined in HIV+ individuals and was tested here using the Game of Dice Task (GDT). We examined decision making under explicit risk in the GDT in 20 HIV+ individuals without substance use disorder or HCV coinfection, including a demographically matched healthy control group (n = 20). Groups were characterized on a standard neuropsychological test battery. For the HIV+ group, several disease-related parameters (viral load, current and nadir CD4 T-cell count) were included. Analyses focused on the GDT and spanned between-group (t-tests; analysis of covariance, ANCOVA) as well as within-group comparisons (Pearson/Spearman correlations). HIV+ individuals were impaired in the GDT, compared to healthy controls (p = .02). Their decision-making impairments were characterized by less advantageous choices and more random choice strategies, especially towards the end of the task. Deficits in the GDT in the HIV+ group were related to executive dysfunctions, slowed processing/motor speed, and current immune system status (CD4+ T-cell levels, ps Decision making under explicit risk in the GDT can occur in HIV-infected individuals without comorbidities. The correlational patterns may point to underlying fronto-subcortical dysfunctions in HIV+ individuals. The GDT provides a useful measure to assess risky decision making in this population and should be tested in larger studies.

The constitutional protection of trade secrets and patents under the Biologics Price Competition and Innovation Act of 2009.

Science.gov (United States)

Epstein, Richard A

2011-01-01

The Biologics Price Competition and Innovation Act of 2009 ("Biosimilars Act") is for the field of pharmaceutical products the single most important legislative development since passage of the Drug Price Competition and Patent Term Restoration Act of 1984 ("Hatch-Waxman Act"), on which portions of the Biosimilars Act are clearly patterned. Congress revised section 351 of the Public Health Service Act (PHSA) to create a pathway for FDA approval of "biosimilar" biological products. Each biosimilar applicant is required to cite in its application a "reference product" that was approved on the basis of a full application containing testing data and manufacturing information, which is owned and was submitted by another company and much of which constitutes trade secret information subject to constitutional protection. Because the Biosimilars Act authorizes biosimilar applicants to cite these previously approved applications, the implementation of the new legislative scheme raises critical issues under the Fifth Amendment of the Constitution, pursuant to which private property--trade secrets included--may not be taken for public use, without "just compensation." FDA must confront those issues as it implements the scheme set out in the Biosimilars Act. This article will discuss these issues, after providing a brief overview of the Biosimilars Act and a more detailed examination of the law of trade secrets.

Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.

Science.gov (United States)

Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S

2014-01-01

Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Encephalitis associated with inappropriate antidiuretic hormone secretion due to chikungunya infection in Recife, State of Pernambuco, Brazil

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Norma Lucena-Silva

Full Text Available Abstract The symptoms of chikungunya virus (CHIKV infection include fever, headache, muscle aches, skin rash, and polyarthralgia, characterized by intense pain, edema, and temporary functional impairment. This is the first report of encephalitis caused by CHIKV infection associated with an atypical presentation of syndrome of inappropriate antidiuretic hormone secretion, evolving to cognitive impairment and apraxia of speech.

Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients but not in Helicobacter pylori-positive healthy subjects

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, Jens; Frøkiaer, H

1996-01-01

BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality was pres......BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality...... was present also in the stomach of DU patients. METHODS: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE2 were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H. pylori-positive). RESULTS: In healthy...... for the abnormally high gastric secretion of bicarbonate in inactive DU patients. The defective duodenal secretion of bicarbonate observed in these patients may be a consequence of previous ulceration rather than the mere presence of H. pylori infection....

Systematic review: Helicobacter pylori infection and impaired drug absorption.

Science.gov (United States)

Lahner, E; Annibale, B; Delle Fave, G

2009-02-15

Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor VII deficiency cause impaired secretion through ineffective translocation and extensive intracellular degradation of factor VII.

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Suzuki, Keijiro; Sugawara, Takeshi; Ishida, Yoji; Suwabe, Akira

2013-02-01

Congenital coagulation factor VII (FVII) deficiency is a rare coagulation disease. We investigated the molecular mechanisms of this FVII deficiency in a patient with compound heterozygous mutations. A 22-year-old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We analyzed the F7 gene of this patient and characterized mutant FVII proteins using in vitro expression studies. Sequence analysis revealed that the patient was compound heterozygous with a point mutation (p.Leu13Pro) in the central hydrophobic core of the signal peptides and a novel non-sense mutation (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not secreted into the medium. Pulse-chase experiments revealed that both mutants were extensively degraded intracellularly compared to wild type. The majority of FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small amount of FVII13P was processed normally with post-translational modifications and was secreted into the medium. The fact that FVII294X was observed only in ER suggests that it is retained in ER. Proteasome apparently plays a central role in these degradations. These findings demonstrate that both mutant FVIIs impaired secretion through ineffective translocation to and retention in ER with extensive intracellular degradation, resulting in an insufficient phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

Security of a kind of quantum secret sharing with entangled states.

Science.gov (United States)

Wang, Tian-Yin; Liu, Ying-Zhao; Wei, Chun-Yan; Cai, Xiao-Qiu; Ma, Jian-Feng

2017-05-30

We present a new collusion attack to a kind of quantum secret sharing schemes with entangled states. Using this attack, an unauthorized set of agents can gain access to the shared secret without the others' cooperation. Furthermore, we establish a general model for this kind of quantum secret sharing schemes and then give some necessary conditions to design a secure quantum secret sharing scheme under this model.

Renal renin secretion as regulator of body fluid homeostasis

DEFF Research Database (Denmark)

Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane

2013-01-01

The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

Open Secrets

OpenAIRE

Madison, Michael

2017-01-01

The law of trade secrets is often conceptualized in bilateral terms, as creating and enforcing rights between trade secret owners, on the one hand, and misappropriators on the other hand. This paper, a chapter in a forthcoming collection on the law of trade secrets, argues that trade secrets and the law that guards them can serve structural and insitutional roles as well. Somewhat surprisingly, given the law’s focus on secrecy, among the institutional products of trade secrets law are commons...

Difficulty understanding speech in noise by the hearing impaired: underlying causes and technological solutions.

Science.gov (United States)

Healy, Eric W; Yoho, Sarah E

2016-08-01

A primary complaint of hearing-impaired individuals involves poor speech understanding when background noise is present. Hearing aids and cochlear implants often allow good speech understanding in quiet backgrounds. But hearing-impaired individuals are highly noise intolerant, and existing devices are not very effective at combating background noise. As a result, speech understanding in noise is often quite poor. In accord with the significance of the problem, considerable effort has been expended toward understanding and remedying this issue. Fortunately, our understanding of the underlying issues is reasonably good. In sharp contrast, effective solutions have remained elusive. One solution that seems promising involves a single-microphone machine-learning algorithm to extract speech from background noise. Data from our group indicate that the algorithm is capable of producing vast increases in speech understanding by hearing-impaired individuals. This paper will first provide an overview of the speech-in-noise problem and outline why hearing-impaired individuals are so noise intolerant. An overview of our approach to solving this problem will follow.

Secretion of hepatic triglycerides into plasma of rats fed retinol

International Nuclear Information System (INIS)

Ahuja, H.C.; Misra, U.K.

1975-01-01

The effect of feeding 33 mg of retinol daily for two days on liver and plasma lipids of rats has been studied. The secretion of liver TG into plasma of retinol fed rats has been measured by the use of palmitic acid-1- 14 C and of Triton WR 1339. Liver and plasma lipids, TG, phospholipids and PC were significantly higher in retinol fed rats as compared to control rats. The incorporation of palmitic acid-1- 14 C into liver TG, PC and PE was significantly higher in retinol fed rats. The labelling pattern with time of liver and plasma TG and PC shows that the secretion of liver TG and PC into plasma was impaired in retinol fed rats. (auth.)

Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers.

Science.gov (United States)

Ciro, D'Orazio; Padoan, Rita; Blau, Hannah; Marostica, Anna; Fuoti, Maurizio; Volpi, Sonia; Pilotta, Alba; Meyerovitch, Joseph; Sher, Daniel; Assael, Baroukh M

2013-03-01

Growth delay in cystic fibrosis is frequent and is usually the result of several interacting causes. It most often derives from severe respiratory impairment and severe malabsorption. There are however patients whose clinical condition is not severe enough to be held accountable for this phenomenon. We aimed at describing patients who showed growth delay, who were not affected by severe pulmonary disease or malabsorption and who, when tested, showed a reduced GH secretion after stimulation with conventional agents. We noticed a disproportionately large prevalence of growth hormone (GH) release deficit (GHRD) in pediatric cystic fibrosis (CF) patients. We examined all patients under our care in the period 2006-11, who were older than 5 and younger than 16 years old. We focussed on those who fell below the 3rd height percentile, or whose growth during the previous 18 months faltered by >2SD, and who did not present clinical conditions that could reasonably explain their failure to thrive. These patients were subjected to standard GH provocative tests. Out of 285 who matched the age criterion, 33 patients also matched the height percentile criterion. While 15/33 suffered clinical conditions that could reasonably explain their failure to thrive, 18/33 underwent GH release provocative tests and 12/18 showed a release deficit. We conclude that impaired GH secretion is more frequent among CF patients compared to the prevalence of GH deficiency in the general population and that GH release impairment may be an independent cause of growth delay in CF. Our findings are in agreement with recent studies that have described low GH levels in CF piglets and in neonates with CF [1]. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

20 CFR 220.184 - If the annuitant becomes disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... impairment(s). 220.184 Section 220.184 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... Activity or Medical Improvement § 220.184 If the annuitant becomes disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which the last impairment(s) ends, the Board...

Age-dependent impairment of auditory processing under spatially focused and divided attention: an electrophysiological study.

Science.gov (United States)

Wild-Wall, Nele; Falkenstein, Michael

2010-01-01

By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.

The RhoGAP Stard13 controls insulin secretion through F-actin remodeling

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Heike Naumann

2018-02-01

Full Text Available Objective: Actin cytoskeleton remodeling is necessary for glucose-stimulated insulin secretion in pancreatic β-cells. A mechanistic understanding of actin dynamics in the islet is paramount to a better comprehension of β-cell dysfunction in diabetes. Here, we investigate the Rho GTPase regulator Stard13 and its role in F-actin cytoskeleton organization and islet function in adult mice. Methods: We used Lifeact-EGFP transgenic animals to visualize actin cytoskeleton organization and dynamics in vivo in the mouse islets. Furthermore, we applied this model to study actin cytoskeleton and insulin secretion in mutant mice deleted for Stard13 selectively in pancreatic cells. We isolated transgenic islets for 3D-imaging and perifusion studies to measure insulin secretion dynamics. In parallel, we performed histological and morphometric analyses of the pancreas and used in vivo approaches to study glucose metabolism in the mouse. Results: In this study, we provide the first genetic evidence that Stard13 regulates insulin secretion in response to glucose. Postnatally, Stard13 expression became restricted to the mouse pancreatic islets. We showed that Stard13 deletion results in a marked increase in actin polymerization in islet cells, which is accompanied by severe reduction of insulin secretion in perifusion experiments. Consistently, Stard13-deleted mice displayed impaired glucose tolerance and reduced glucose-stimulated insulin secretion. Conclusions: Taken together, our results suggest a previously unappreciated role for the RhoGAP protein Stard13 in the interplay between actin cytoskeletal remodeling and insulin secretion. Keywords: F-actin, Insulin secretion, Islet, Pancreas, Lifeact, Stard13

Impaired decision-making under risk is associated with gaming-specific inhibition deficits among college students with Internet gaming disorder.

Science.gov (United States)

Yao, Yuan-Wei; Wang, Ling-Jiao; Yip, Sarah W; Chen, Pin-Ru; Li, Song; Xu, Jiansong; Zhang, Jin-Tao; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

2015-09-30

A growing body of evidence indicates that both inhibition and decision-making deficits play essential roles in the development and maintenance of Internet gaming disorder (IGD). Clarifying whether impaired decision-making among individuals with IGD is related to poor inhibition will advance our understanding of IGD and contribute to intervention development. However, the relationship between these two functions remains unclear. In this study, we sought to systemically examine inhibitory processes, decision-making and the relationship between the two among individuals with IGD. Thirty-four individuals with IGD and 32 matched healthy controls (HCs) were recruited. In comparison to HCs, IGD subjects demonstrated inhibition deficits during performance of the gaming-related Go/No-Go task and impaired decision-making under risk. In addition, errors on No-Go trials during the gaming-related Go/No-Go task were positively associated with decision-making impairments under risk but not under ambiguity among IGD subjects. These results suggest individuals with IGD are impaired in some aspects of inhibition and decision-making functions, and that decision-making deficits under risk are linked to poor inhibition specifically related to gaming cues, which has implications for the development of novel intervention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Intra-islet glucagon secretion and action in the regulation of glucose homeostasis.

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Qinghua eWang

2013-01-01

Full Text Available Glucagon, a key hormone in the regulation of glucose homeostasis, acts as a counter-regulatory hormone to insulin by promoting hepatic glucose output. Under normal conditions, insulin and glucagon operate in concert to maintain the glucose level within a narrow physiological range. In diabetes, however, while insulin secretion or action is insufficient, the production and secretion of glucagon are excessive, contributing to the development of diabetic hyperglycemia. Within an islet, intra-islet insulin, in cooperation with intra-islet GABA, suppresses glucagon secretion via direct modulation of -cell intracellular signaling pathways involving Akt activation, GABA receptor phosphorylation and the receptor plasma membrane translocation, while intra-islet glucagon plays an important role in modulating β-cell function and insulin secretion. Defects in the insulin-glucagon fine-tuning machinery may result in β-cell glucose incompetence, leading to unsuppressed glucagon secretion and subsequent hyperglycemia, which often occur under extreme conditions of glucose influx or efflux. Therefore, deciphering the precise molecular mechanisms underlying glucagon secretion and action will facilitate our understanding of glucagon physiology, in particular, its role in regulating islet β-cell function, and hence the mechanisms behind body glucose homeostasis.

Seasonal prolactin secretion and its role in seasonal reproduction: a review.

Science.gov (United States)

Curlewis, J D

1992-01-01

The majority of seasonally breeding mammals show a seasonal pattern of prolactin secretion with peak concentrations in spring or summer and a nadir in autumn or winter. Photoperiod influences prolactin secretion via its effects on the secretion of the pineal hormone melatonin. Preliminary evidence suggests that the effects of melatonin on both prolactin and gonadotrophin secretion are via a common target area, possibly within the anterior hypothalamus, and that differences in response to photoperiod may be due to differences in the processing and/or interpretation of the melatonin signal. In contrast to seasonal gonadotrophin secretion, the seasonal changes in prolactin are not due to changes in the sensitivity of a feedback loop and so must be due to direct effects on the hypothalamic pathways that control prolactin secretion. Little else can be said with confidence about the neuroendocrine mechanisms that lead to the seasonal changes in prolactin secretion. Dopamine and noradrenaline turnover in the arcuate nucleus and median eminence decrease under short daylength. If catecholamine turnover in these structures is positively correlated with catecholamine concentrations in the long or short hypophysial portal vessels, it is unlikely that the decrease in prolactin concentration in winter is due to the effects of increased concentrations of dopamine or noradrenaline in the portal vessels. There is, however, evidence for increased pituitary sensitivity to dopamine under short daylength, so increased dopamine concentrations may not be required for suppression of prolactin secretion at this time. In addition to the diminished secretion of prolactin under short daylength, rate of prolactin synthesis and pituitary content of prolactin also decline although the mechanisms that regulate these changes are poorly understood. Although all seasonal breeders show a seasonal change in prolactin secretion, there are continuously breeding species in which prolactin secretion is

Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets

Energy Technology Data Exchange (ETDEWEB)

Alquier, Thierry; Peyot, Marie-Line; Latour, M. G.; Kebede, Melkam; Sorensen, Christina M.; Gesta, Stephane; Kahn, C. R.; Smith, Richard D.; Jetton, Thomas L.; Metz, Thomas O.; Prentki, Marc; Poitout, Vincent J.

2009-11-01

The G protein-coupled receptor GPR40 mediates fatty-acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. We observed that glucose- and arginine-stimulated insulin secretion, assessed by hyperglycemic clamps, was decreased by approximately 60% in GPR40 knock-out (KO) fasted and fed mice, without changes in insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps. Glucose and palmitate metabolism were not affected by GPR40 deletion. Lipid profiling revealed a similar increase in triglyceride and decrease in lysophosphatidylethanolamine species in WT and KO islets in response to palmitate. These results demonstrate that GPR40 regulates insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism.

Applying secret sharing for HIS backup exchange.

Science.gov (United States)

Kuroda, Tomohiro; Kimura, Eizen; Matsumura, Yasushi; Yamashita, Yoshinori; Hiramatsu, Haruhiko; Kume, Naoto; Sato, Atsushi

2013-01-01

To secure business continuity is indispensable for hospitals to fulfill its social responsibility under disasters. Although to back up the data of the hospital information system (HIS) at multiple remote sites is a key strategy of business continuity plan (BCP), the requirements to treat privacy sensitive data jack up the cost for the backup. The secret sharing is a method to split an original secret message up so that each individual piece is meaningless, but putting sufficient number of pieces together to reveal the original message. The secret sharing method eases us to exchange HIS backups between multiple hospitals. This paper evaluated the feasibility of the commercial secret sharing solution for HIS backup through several simulations. The result shows that the commercial solution is feasible to realize reasonable HIS backup exchange platform when template of contract between participating hospitals is ready.

PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

Science.gov (United States)

Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

2014-02-01

Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

Quantitative gait analysis under dual-task in older people with mild cognitive impairment: a reliability study

Directory of Open Access Journals (Sweden)

Gutmanis Iris

2009-09-01

Full Text Available Abstract Background Reliability of quantitative gait assessment while dual-tasking (walking while doing a secondary task such as talking in people with cognitive impairment is unknown. Dual-tasking gait assessment is becoming highly important for mobility research with older adults since better reflects their performance in the basic activities of daily living. Our purpose was to establish the test-retest reliability of assessing quantitative gait variables using an electronic walkway in older adults with mild cognitive impairment (MCI under single and dual-task conditions. Methods The gait performance of 11 elderly individuals with MCI was evaluated using an electronic walkway (GAITRite® System in two sessions, one week apart. Six gait parameters (gait velocity, step length, stride length, step time, stride time, and double support time were assessed under two conditions: single-task (sG: usual walking and dual-task (dG: counting backwards from 100 while walking. Test-retest reliability was determined using intra-class correlation coefficient (ICC. Gait variability was measured using coefficient of variation (CoV. Results Eleven participants (average age = 76.6 years, SD = 7.3 were assessed. They were high functioning (Clinical Dementia Rating Score = 0.5 with a mean Mini-Mental Status Exam (MMSE score of 28 (SD = 1.56, and a mean Montreal Cognitive Assessment (MoCA score of 22.8 (SD = 1.23. Under dual-task conditions, mean gait velocity (GV decreased significantly (sGV = 119.11 ± 20.20 cm/s; dGV = 110.88 ± 19.76 cm/s; p = 0.005. Additionally, under dual-task conditions, higher gait variability was found on stride time, step time, and double support time. Test-retest reliability was high (ICC>0.85 for the six parameters evaluated under both conditions. Conclusion In older people with MCI, variability of time-related gait parameters increased with dual-tasking suggesting cognitive control of gait performance. Assessment of quantitative gait

Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

Science.gov (United States)

Araya, S; Kuster, E; Gluch, D; Mariotta, L; Lutz, C; Reding, T V; Graf, R; Verrey, F; Camargo, S M R

2018-04-01

Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state, Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs, and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern, the rate of Glu influx into acinar cells was approximately sixfold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln

A translocator-specific export signal establishes the translocator-effector secretion hierarchy that is important for type III secretion system function

Science.gov (United States)

Tomalka, Amanda G.; Stopford, Charles M.; Lee, Pei-Chung; Rietsch, Arne

2012-01-01

Summary Type III secretion systems are used by many Gram-negative pathogens to directly deliver effector proteins into the cytoplasm of host cells. To accomplish this, bacteria secrete translocator proteins that form a pore in the host-cell membrane through which the effector proteins are then introduced into the host cell. Evidence from multiple systems indicates that the pore-forming translocator proteins are exported before effectors, but how this secretion hierarchy is established is unclear. Here we used the P. aeruginosa translocator protein PopD as a model to identify its export signals. The amino-terminal secretion signal and chaperone, PcrH, are required for export under all conditions. Two novel signals in PopD, one proximal to the chaperone-binding site and one at the very C-terminus of the protein, are required for export of PopD before effector proteins. These novel export signals establish the translocator-effector secretion hierarchy, which in turn, is critical for the delivery of effectors into host cells. PMID:23121689

Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.

Science.gov (United States)

Mahanty, Siddhartha; Hutchinson, Karen; Agarwal, Sudhanshu; McRae, Michael; Rollin, Pierre E; Pulendran, Bali

2003-03-15

Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

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Yosefu Arime

Full Text Available Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days of either saline or PCP (10 mg/kg: (1 a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2 brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

Secret key distillation from shielded two-qubit states

International Nuclear Information System (INIS)

Bae, Joonwoo

2010-01-01

The quantum states corresponding to a secret key are characterized using the so-called private states, where the key part consisting of a secret key is shielded by the additional systems. Based on the construction, it was shown that a secret key can be distilled from bound entangled states. In this work, I consider the shielded two-qubit states in a key-distillation scenario and derive the conditions under which a secret key can be distilled using the recurrence protocol or the two-way classical distillation, advantage distillation together with one-way postprocessing. From the security conditions, it is shown that a secret key can be distilled from bound entangled states in a much wider range. In addition, I consider the case that in which white noise is added to quantum states and show that the classical distillation protocol still works despite a certain amount of noise although the recurrence protocol does not.

On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

Directory of Open Access Journals (Sweden)

Wang Daoshun

2010-01-01

Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

Authentication Without Secrets

Energy Technology Data Exchange (ETDEWEB)

Pierson, Lyndon G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robertson, Perry J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-11-01

This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

Pancreatic β-Cell Electrical Activity and Insulin Secretion: of Mice and Men

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Rorsman, Patrik; Ashcroft, Frances M

2018-01-01

The pancreatic β-cell plays a key role in glucose homeostasis by secreting insulin, the only hormone capable of lowering the blood glucose concentration. Impaired insulin secretion results in the chronic hyperglycaemia that characterizes type 2 diabetes (T2DM), which currently afflicts >450 million people worldwide. The healthy β-cell acts as a glucose sensor matching its output to the circulating glucose concentration. It does so via metabolically induced changes in electrical activity, which culminate in an increase in the cytoplasmic Ca2+ concentration and initiation of Ca2+-dependent exocytosis of insulin-containing secretory granules. Here, we review recent advances in our understanding of the β-cell transcriptome, electrical activity and insulin exocytosis. We highlight salient differences between mouse and human β-cells, provide models of how the different ion channels contribute to their electrical activity and insulin secretion, and conclude by discussing how these processes become perturbed in T2DM. PMID:29212789

Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion.

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Patterson, Jessica N; Cousteils, Katelyn; Lou, Jennifer W; Manning Fox, Jocelyn E; MacDonald, Patrick E; Joseph, Jamie W

2014-05-09

It is well known that mitochondrial metabolism of pyruvate is critical for insulin secretion; however, we know little about how pyruvate is transported into mitochondria in β-cells. Part of the reason for this lack of knowledge is that the carrier gene was only discovered in 2012. In the current study, we assess the role of the recently identified carrier in the regulation of insulin secretion. Our studies show that β-cells express both mitochondrial pyruvate carriers (Mpc1 and Mpc2). Using both pharmacological inhibitors and siRNA-mediated knockdown of the MPCs we show that this carrier plays a key role in regulating insulin secretion in clonal 832/13 β-cells as well as rat and human islets. We also show that the MPC is an essential regulator of both the ATP-regulated potassium (KATP) channel-dependent and -independent pathways of insulin secretion. Inhibition of the MPC blocks the glucose-stimulated increase in two key signaling molecules involved in regulating insulin secretion, the ATP/ADP ratio and NADPH/NADP(+) ratio. The MPC also plays a role in in vivo glucose homeostasis as inhibition of MPC by the pharmacological inhibitor α-cyano-β-(1-phenylindol-3-yl)-acrylate (UK5099) resulted in impaired glucose tolerance. These studies clearly show that the newly identified mitochondrial pyruvate carrier sits at an important branching point in nutrient metabolism and that it is an essential regulator of insulin secretion.

Device-independent secret-key-rate analysis for quantum repeaters

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Holz, Timo; Kampermann, Hermann; Bruß, Dagmar

2018-01-01

The device-independent approach to quantum key distribution (QKD) aims to establish a secret key between two or more parties with untrusted devices, potentially under full control of a quantum adversary. The performance of a QKD protocol can be quantified by the secret key rate, which can be lower bounded via the violation of an appropriate Bell inequality in a setup with untrusted devices. We study secret key rates in the device-independent scenario for different quantum repeater setups and compare them to their device-dependent analogon. The quantum repeater setups under consideration are the original protocol by Briegel et al. [Phys. Rev. Lett. 81, 5932 (1998), 10.1103/PhysRevLett.81.5932] and the hybrid quantum repeater protocol by van Loock et al. [Phys. Rev. Lett. 96, 240501 (2006), 10.1103/PhysRevLett.96.240501]. For a given repeater scheme and a given QKD protocol, the secret key rate depends on a variety of parameters, such as the gate quality or the detector efficiency. We systematically analyze the impact of these parameters and suggest optimized strategies.

Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

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Rebecca L Schmidt

Full Text Available Inflammasome activation permits processing of interleukins (IL-1β and 18 and elicits cell death (pyroptosis. Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1 activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm p60 protein. Primed murine dendritic cells (DCs responded to p60 stimulation with reactive oxygen species (ROS production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes.

Effect of Magnesium Supplements on Insulin Secretion After Kidney Transplantation: A Randomized Controlled Trial.

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Van Laecke, Steven; Caluwe, Rogier; Huybrechts, Inge; Nagler, Evi V; Vanholder, Raymond; Peeters, Patrick; Van Vlem, Bruno; Van Biesen, Wim

2017-08-29

BACKGROUND Hypomagnesemia is associated with a disturbed glucose metabolism. Insulin hypo-secretion predicts diabetes in the general population and in transplant recipients. We aimed to assess whether magnesium improves insulin secretion and glycemic control after transplantation in prevalent hypomagnesemic kidney transplant recipients. MATERIAL AND METHODS We conducted an open-label, randomized, parallel-group study. Eligible participants were adults more than 4 months after kidney transplantation on tacrolimus with persisting serum magnesium concentrations food-frequency questionnaire. All analyses were done on an intention-to-treat basis. RESULTS Magnesium with a mean daily dose of 688±237mg in the treatment group failed to lead to significant differences between the 2 groups in FPIR, fasting glucose, HbA1c, or HOMA-IR. Persisting hypomagnesemia was very common and associated with more insulin hypo-secretion, glucose intolerance, and lower dietary magnesium intake (142±56 versus 202±90 mg; p=0.015) as compared to patients with a rise in serum magnesium over 6 months. CONCLUSIONS Magnesium supplementation does not improve insulin secretion in stable hypomagnesemic kidney transplant recipients on tacrolimus. Persisting hypomagnesemia is associated with impaired glucose tolerance, insulin hypo-secretion, and dietary factors.

Studies quantifying modulatory effects of inhaled NO2 and SO2 on tracheal mucus secretion, proliferative activity of airway epithelium and architecture of lung parenchyma

International Nuclear Information System (INIS)

Wagner, U.; Barth, P.J.; Bredenbroeker, D.; Haase, H.; Locher, A.; Janssen, P.; Yu, F.; Wichert, P. von

1995-10-01

The following studies were designed to quantify changes in tracheal mucus secretion and epithelial proliferation of peripheral airways induced by inhaled NO 2 and SO 2 . Groups of male Sprague-Dawley rats were exposed alternatively to 1, 5, 10 and 20 ppm NO 2 and SO 2 the exposure-time being 3 or 25 days (d) respectively. Studies of tracheal mucus secretion radiolabelling mucins with 35 S clearly demonstrated a concentration dependant modulation of mucus secretion. We were able to demonstrate for the first time a significant increase of mucus secretion due to submucosal application of the peptide hormone GLP-1(7-36)amide. We were able to demonstrate amylin to be a potent secretagogue, dose-dependently stimulating mucus secretion. Our morphologic data reveal the effects caused by concentrations between 4-5 ppm NO 2 to be so small, that they are hardly detectable at light microscopic level. The assessment of proliferative activity, however, clearly demonstrates an increased proliferation due to even lower concentrations indicating, that even 1 ppm is able to cause epithelial impairment with consecutive regeneration. Double-labelling techniques of proliferation markers and the 10 kD Clara cell specific antigen reveal the Clara cell to be the only source for epithelial regeneration in peripheral airways under the reported experimental conditions of this study. (orig.) [de

20 CFR 30.902 - How will OWCP calculate the amount of the award of impairment benefits that is payable under Part E?

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2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false How will OWCP calculate the amount of the award of impairment benefits that is payable under Part E? 30.902 Section 30.902 Employees' Benefits... § 30.902 How will OWCP calculate the amount of the award of impairment benefits that is payable under...

Lipids in airway secretions

International Nuclear Information System (INIS)

Bhaskar, K.R.; DeFeudis O'Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

1987-01-01

Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO 2 , (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14 C acetate and 14 C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

Arsenite reduces insulin secretion in rat pancreatic β-cells by decreasing the calcium-dependent calpain-10 proteolysis of SNAP-25

International Nuclear Information System (INIS)

Diaz-Villasenor, Andrea; Burns, Anna L.; Salazar, Ana Maria; Sordo, Monserrat; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

2008-01-01

An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic β-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca 2+ ]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 μM). The global activity of calpains increased with 2 μM arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 μM arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the β cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca 2+ ]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion

Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

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Valborg Gudmundsdottir

Full Text Available Glucagon-like peptide 1 (GLP-1 stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126. This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100. Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P < 0.05 with glucose-stimulated insulin secretion phenotypes in up to 5,318 individuals in MAGIC cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one of the target tissues of GLP-1 and we thus hypothesized that similar networks might be functional in both tissues. In order to verify peripheral effects of GLP-1 stimulation, we compared the transcriptome profiling of ob/ob mice treated with liraglutide, a clinically used GLP-1 receptor agonist, versus baseline controls. Some of the upstream regulators of differentially expressed genes in the white adipose tissue of ob/ob mice were also detected in the human beta-cell network of genes associated with GLP-1 stimulated insulin secretion. The findings provide biological insight into the mechanisms through which the effects of GLP-1 may be modulated and highlight a potential role of the beta-cell expressed genes RYR2, GDI2, KIAA0232, COL4A1 and COL4A2 in GLP-1 stimulated

Chronic suppression of acetyl-CoA carboxylase 1 in beta-cells impairs insulin secretion via inhibition of glucose rather than lipid metabolism.

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Ronnebaum, Sarah M; Joseph, Jamie W; Ilkayeva, Olga; Burgess, Shawn C; Lu, Danhong; Becker, Thomas C; Sherry, A Dean; Newgard, Christopher B

2008-05-23

Acetyl-CoA carboxylase 1 (ACC1) currently is being investigated as a target for treatment of obesity-associated dyslipidemia and insulin resistance. To investigate the effects of ACC1 inhibition on insulin secretion, three small interfering RNA (siRNA) duplexes targeting ACC1 (siACC1) were transfected into the INS-1-derived cell line, 832/13; the most efficacious duplex was also cloned into an adenovirus and used to transduce isolated rat islets. Delivery of the siACC1 duplexes decreased ACC1 mRNA by 60-80% in 832/13 cells and islets and enzyme activity by 46% compared with cells treated with a non-targeted siRNA. Delivery of siACC1 decreased glucose-stimulated insulin secretion (GSIS) by 70% in 832/13 cells and by 33% in islets. Surprisingly, siACC1 treatment decreased glucose oxidation by 49%, and the ATP:ADP ratio by 52%, accompanied by clear decreases in pyruvate cycling activity and tricarboxylic acid cycle intermediates. Exposure of siACC1-treated cells to the pyruvate cycling substrate dimethylmalate restored GSIS to normal without recovery of the depressed ATP:ADP ratio. In siACC1-treated cells, glucokinase protein levels were decreased by 25%, which correlated with a 36% decrease in glycogen synthesis and a 33% decrease in glycolytic flux. Furthermore, acute addition of the ACC1 inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) to beta-cells suppressed [(14)C]glucose incorporation into lipids but had no effect on GSIS, whereas chronic TOFA administration suppressed GSIS and glucose metabolism. In sum, chronic, but not acute, suppression of ACC1 activity impairs GSIS via inhibition of glucose rather than lipid metabolism. These findings raise concerns about the use of ACC inhibitors for diabetes therapy.

Chronic Suppression of Acetyl-CoA Carboxylase 1 in β-Cells Impairs Insulin Secretion via Inhibition of Glucose Rather Than Lipid Metabolism*

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Ronnebaum, Sarah M.; Joseph, Jamie W.; Ilkayeva, Olga; Burgess, Shawn C.; Lu, Danhong; Becker, Thomas C.; Sherry, A. Dean; Newgard, Christopher B.

2008-01-01

Acetyl-CoA carboxylase 1 (ACC1) currently is being investigated as a target for treatment of obesity-associated dyslipidemia and insulin resistance. To investigate the effects of ACC1 inhibition on insulin secretion, three small interfering RNA (siRNA) duplexes targeting ACC1 (siACC1) were transfected into the INS-1-derived cell line, 832/13; the most efficacious duplex was also cloned into an adenovirus and used to transduce isolated rat islets. Delivery of the siACC1 duplexes decreased ACC1 mRNA by 60–80% in 832/13 cells and islets and enzyme activity by 46% compared with cells treated with a non-targeted siRNA. Delivery of siACC1 decreased glucose-stimulated insulin secretion (GSIS) by 70% in 832/13 cells and by 33% in islets. Surprisingly, siACC1 treatment decreased glucose oxidation by 49%, and the ATP:ADP ratio by 52%, accompanied by clear decreases in pyruvate cycling activity and tricarboxylic acid cycle intermediates. Exposure of siACC1-treated cells to the pyruvate cycling substrate dimethylmalate restored GSIS to normal without recovery of the depressed ATP:ADP ratio. In siACC1-treated cells, glucokinase protein levels were decreased by 25%, which correlated with a 36% decrease in glycogen synthesis and a 33% decrease in glycolytic flux. Furthermore, acute addition of the ACC1 inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) to β-cells suppressed [14C]glucose incorporation into lipids but had no effect on GSIS, whereas chronic TOFA administration suppressed GSIS and glucose metabolism. In sum, chronic, but not acute, suppression of ACC1 activity impairs GSIS via inhibition of glucose rather than lipid metabolism. These findings raise concerns about the use of ACC inhibitors for diabetes therapy. PMID:18381287

20 CFR 220.102 - Non-severe impairment(s), defined.

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2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Non-severe impairment(s), defined. 220.102 Section 220.102 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... these include— (1) Physical functions such as walking, standing, sitting, lifting, pushing, pulling...

L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2.

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Nakatsu, Daiki; Horiuchi, Yuta; Kano, Fumi; Noguchi, Yoshiyuki; Sugawara, Taichi; Takamoto, Iseki; Kubota, Naoto; Kadowaki, Takashi; Murata, Masayuki

2015-03-10

Increase in the concentration of plasma L-cysteine is closely associated with defective insulin secretion from pancreatic β-cells, which results in type 2 diabetes (T2D). In this study, we investigated the effects of prolonged L-cysteine treatment on glucose-stimulated insulin secretion (GSIS) from mouse insulinoma 6 (MIN6) cells and from mouse pancreatic islets, and found that the treatment reversibly inhibited glucose-induced ATP production and resulting GSIS without affecting proinsulin and insulin synthesis. Comprehensive metabolic analyses using capillary electrophoresis time-of-flight mass spectrometry showed that prolonged L-cysteine treatment decreased the levels of pyruvate and its downstream metabolites. In addition, methyl pyruvate, a membrane-permeable form of pyruvate, rescued L-cysteine-induced inhibition of GSIS. Based on these results, we found that both in vitro and in MIN6 cells, L-cysteine specifically inhibited the activity of pyruvate kinase muscle isoform 2 (PKM2), an isoform of pyruvate kinases that catalyze the conversion of phosphoenolpyruvate to pyruvate. L-cysteine also induced PKM2 subunit dissociation (tetramers to dimers/monomers) in cells, which resulted in impaired glucose-induced ATP production for GSIS. DASA-10 (NCGC00181061, a substituted N,N'-diarylsulfonamide), a specific activator for PKM2, restored the tetramer formation and the activity of PKM2, glucose-induced ATP production, and biphasic insulin secretion in L-cysteine-treated cells. Collectively, our results demonstrate that impaired insulin secretion due to exposure to L-cysteine resulted from its direct binding and inactivation of PKM2 and suggest that PKM2 is a potential therapeutic target for T2D.

Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

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van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

2011-01-01

OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

A catalogue of human secreted proteins and its implications

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Shivakumar Keerthikumar

2016-11-01

Full Text Available Under both normal and pathological conditions, cells secrete variety of proteins through classical and non-classical secretory pathways into the extracellular space. Majority of these proteins represent pathophysiology of the cell from which it is secreted. Recently, though more than 92% of the protein coding genes has been mapped by human proteome map project, but number of those proteins that constitutes secretome of the cell still remains elusive. Secreted proteins or the secretome can be accessible in bodily fluids and hence are considered as potential biomarkers to discriminate between healthy and diseased individuals. In order to facilitate the biomarker discovery and to further aid clinicians and scientists working in these arenas, we have compiled and catalogued secreted proteins from the human proteome using integrated bioinformatics approach. In this study, nearly 14% of the human proteome is likely to be secreted through classical and non-classical secretory pathways. Out of which, ~38% of these secreted proteins were found in extracellular vesicles including exosomes and shedding microvesicles. Among these secreted proteins, 94% were detected in human bodily fluids including blood, plasma, serum, saliva, semen, tear and urine. We anticipate that this high confidence list of secreted proteins could serve as a compendium of candidate biomarkers. In addition, the catalogue may provide functional insights in understanding the molecular mechanisms involved in various physiological and pathophysiological conditions of the cell.

Gait parameter risk factors for falls under simple and dual task conditions in cognitively impaired older people.

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Taylor, Morag E; Delbaere, Kim; Mikolaizak, A Stefanie; Lord, Stephen R; Close, Jacqueline C T

2013-01-01

Impaired gait may contribute to the increased rate of falls in cognitively impaired older people. We investigated whether gait under simple and dual task conditions could predict falls in this group. The study sample consisted of 64 community dwelling older people with mild to moderate cognitive impairment. Participants walked at their preferred speed under three conditions: (a) simple walking, (b) walking while carrying a glass of water and (c) walking while counting backwards from 30. Spatiotemporal gait parameters were measured using the GAITRite(®) mat. Falls were recorded prospectively for 12months with the assistance of carers. Twenty-two (35%) people fell two or more times in the 12month follow-up period. There was a significant main effect of gait condition and a significant main effect of faller status for mean value measures (velocity, stride length, double support time and stride width) and for variability measures (swing time variability and stride length variability). Examination of individual gait parameters indicated that the multiple fallers walked more slowly, had shorter stride length, spent longer time in double support, had a wider support width and showed more variability in stride length and swing time (p<0.05). There was no significant interaction between gait condition and faller status for any of the gait variables. In conclusion, dual task activities adversely affect gait in cognitively impaired older people. Multiple fallers performed worse in each gait condition but the addition of a functional or cognitive secondary task provided no added benefit in discriminating fallers from non-fallers with cognitive impairment. Copyright © 2012 Elsevier B.V. All rights reserved.

Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells

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Pawin Pongkorpsakol

2017-06-01

Full Text Available Intestinal Cl− secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA suppressed Vibrio cholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl− secretion in human intestinal epithelial (T84 cells. FFA inhibited cAMP-dependent Cl− secretion in T84 cell monolayers with IC50 of ∼8 μM. Other fenamate drugs including tolfenamic acid, meclofenamic acid and mefenamic acid exhibited the same effect albeit with lower potency. FFA also inhibited activities of CFTR, a cAMP-activated apical Cl− channel, and KCNQ1/KCNE3, a cAMP-activated basolateral K+ channel. Mechanisms of CFTR inhibition by FFA did not involve activation of its negative regulators. Interestingly, FFA inhibited Ca2+-dependent Cl− secretion with IC50 of ∼10 μM. FFA inhibited activities of Ca2+-activated Cl− channels and KCa3.1, a Ca2+-activated basolateral K+ channels, but had no effect on activities of Na+–K+–Cl− cotransporters and Na+–K+ ATPases. These results indicate that FFA inhibits both cAMP and Ca2+-dependent Cl− secretion by suppressing activities of both apical Cl− channels and basolateral K+ channels. FFA and other fenamate drugs may be useful in the treatment of secretory diarrheas.

Impaired Glucose Metabolism Despite Decreased Insulin Resistance After Renal Transplantation

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Manfred Hecking

2012-06-01

Full Text Available The pathophysiology underlying new-onset diabetes after transplantation (NODAT is unresolved. We obtained demographics and laboratory data from all 1064 renal transplant recipients followed at our outpatient clinic in 2009/2010, randomly assigned 307 patients without previously diagnosed diabetes to a routine 2-hour oral glucose tolerance test (OGTT, and compared the metabolic results to a large, unrelated cross-sectional cohort of non-transplanted subjects. Among renal transplant recipients, 11% had a history of NODAT, and 12% had type 1 and type 2 diabetes. 42% of all OGTTs were abnormal (9% diabetic, predominantly in older patients who received tacrolimus. Compared to non-transplanted subjects, basal glucose was lower and HbA1c higher in renal transplant patients. Compared to non-transplanted subjects, insulin secretion was inferior, and insulin sensitivity improved at ≥6 months, as well as 3 months post-transplantation:(The Figure shows linear spline interpolation; all p for overall difference between non-Tx and Tx patients <0.02, using likelihood ratio testing. Our results indicate that impaired insulin secretion is the predominant problem after renal transplantation, suggesting benefit for therapeutic regimens that preserve beta cell function after renal transplantation. The mechanism of increased insulin sensitivity might be pathophysiologically similar to pancreatogenic diabetes.fx1

Obesity Impairs the Action of the Neuroendocrine Ghrelin System

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Zigman, Jeffrey M.; Bouret, Sebastien G.; Andrews, Zane B.

2016-01-01

Ghrelin is a metabolic hormone that promotes energy conservation by regulating appetite and energy expenditure. Although some studies suggest that antagonizing ghrelin function attenuates body weight gain and glucose intolerance on a high calorie diet, there is little information about the metabolic actions of ghrelin in the obese state. In this review, we discuss the novel concept of obesity-induced central ghrelin resistance in neural circuits regulating behavior, and impaired ghrelin secretion from the stomach. Interestingly, weight loss restores ghrelin secretion and function, and we hypothesize that ghrelin resistance is a mechanism designed to protect a higher body weight set-point established during times of food availability, to maximize energy reserves during a time of food scarcity. PMID:26542050

The biphasic effect of extracellular glucose concentration on carbachol-induced fluid secretion from mouse submandibular glands.

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Terachi, Momomi; Hirono, Chikara; Kitagawa, Michinori; Sugita, Makoto

2018-06-01

Cholinergic agonists evoke elevations of the cytoplasmic free-calcium concentration ([Ca 2+ ] i ) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh-induced fluid secretion. The CCh-induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium-glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1-mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl - secretion in real-time. High extracellular glucose levels may suppress the CCh-induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca 2+ ] i signals. © 2018 Eur J Oral Sci.

LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

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Matson Jyl S

2008-02-01

Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

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Chen, Chien-Chang; Liu, Chong-An

2013-01-01

A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

Oral administration of royal jelly restores tear secretion capacity in rat blink-suppressed dry eye model by modulating lacrimal gland function.

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Toshihiro Imada

Full Text Available Tears are secreted from the lacrimal gland (LG, a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ, pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.

The relationship between C-type natriuretic peptide and cognitive impairment in older patients with Type 2 diabetes

International Nuclear Information System (INIS)

Li Xinling; Zhu Xiangyang; Huang Huaiyu; Jin Yan

2011-01-01

Objective: To investigate the relationship between C-type natriuretic peptide and cognitive impairment in older patients with type 2 diabetes, and to explore the pathogenesis of diabetic cognitive impairment. Methods: According to the Montreal Cognitive Assessment (MoCA) scores, 80 type 2 diabetic patients over the age of 60 years were divided into two groups, one group including 31 cases with cognitive impairment, the other 49 patients with non-cognitive impairment. And 80 normal participants were selected as the control group. Plasma level of C-type natriuretic peptide was measured by radio-immunity assay in all subjects. The changes and associations of the plasma C-type natriuretic peptide level among three groups was analyzed. Result: In the non-cognitive impairment group, plasma level of C-type natriuretic peptide was higher than that in the control group (P<0.01). But the plasma level of C-type natriuretic peptide in the cognitive impairment group was degraded, significantly deferent with those in the control group and the non-cognitive impairment group (P<0.01). MoCA scores of the cognitive impairment group positively correlated with plasma level of C-type natriuretic peptide (r=0.513, P<0.01). Conclusion: In the early period of type 2 diabetes,the secretion of C-type natriuretic peptide was increased. When diabetic cognitive impairment complicated,the secretion of C-type natriuretic peptide was decompensated. Then plasma level of C-type natriuretic peptide become low. The level of C-type natriuretic peptide closely correlated with diabetic cognitive impairment. It was suggested that diabetic angiopathies may act an important role in the pathogenesis of diabetic cognitive impairment. (authors)

Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places

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Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth

2014-01-01

In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…

Autocrine secretion of tumor necrosis factor under the influence of interferon-γ amplifies HLA-DR gene induction in human monocytes

International Nuclear Information System (INIS)

Arenzana-Seisdedos, F.; Mogensen, S.C.; Vuillier, F.; Fiers, W.; Virelizier, J.L.

1988-01-01

Recombinant interferon-γ (IFN-γ) induced HLA-DR gene expression in both U937 and THP-1 human monocytic cell lines, although the former was only very weakly inducible. Combination of recombinant tumor necrosis factor (TNF) and IFN-γ resulted in a synergistic enhancement of DR mRNA and protein induction in both cell lines. TNF alone increased the constitutive expression of the DR gene in THP-1 cells. In the HLA class II-negative U937 cells, TNF used alone was not able to induce DR gene expression. Such a negative result was not due to a lack of TNF receptor expression in U937 cells, since TNF clearly induced HLA class I and TNF gene expression in this cell line. THP-1, but not U937, cells secreted TNF under the influence of IFN-γ. Neutralization of TNF by a specific antibody decreased IFN-γ-induced DR antigen expression in THP-1 cultures. These observations indicate that TNF is not able to directly induce DR gene expression, but rather amplifies ongoing expression of this gene, whether constitutive or induced by IFN-γ. In the two cell lines tested, the level of DR inducibility under the influence of IFN-γ used alone depended on a different inducibility of TNF secretion by IFN-γ. Altogether, the observations indicate that TNF, whether exogenous or endogenously produced under the influence of IFN-γ, amplifies DR gene expression in monocytes, a phenomenon that may provide to such antigen-presenting cells a selective sensitivity to the DR-inducing effects of IFN-γ

Salmonella-secreted Virulence Factors

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Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

2011-05-01

In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

A Common Structural Motif in the Binding of Virulence Factors to Bacterial Secretion Chaperones

International Nuclear Information System (INIS)

Lilic, M.; Vujanac, M.; Stebbins, C.

2006-01-01

Salmonella invasion protein A (SipA) is translocated into host cells by a type III secretion system (T3SS) and comprises two regions: one domain binds its cognate type III secretion chaperone, InvB, in the bacterium to facilitate translocation, while a second domain functions in the host cell, contributing to bacterial uptake by polymerizing actin. We present here the crystal structures of the SipA chaperone binding domain (CBD) alone and in complex with InvB. The SipA CBD is found to consist of a nonglobular polypeptide as well as a large globular domain, both of which are necessary for binding to InvB. We also identify a structural motif that may direct virulence factors to their cognate chaperones in a diverse range of pathogenic bacteria. Disruption of this structural motif leads to a destabilization of several chaperone-substrate complexes from different species, as well as an impairment of secretion in Salmonella

Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

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Moorkens, G; Berwaerts, J; Wynants, H; Abs, R

2000-07-01

Previous studies have revealed that hormonal disturbances may accompany the chronic fatigue syndrome (CFS). Changes in the secretion of the pituitary-adrenal axis have been demonstrated, as well as abnormalities in the GH-IGF-I axis. However, data have not always been well characterized and were sometimes conflicting. The small number of CFS patients investigated in earlier studies may have played a role in the interpretation of the results. Hormonal testing was performed in 73 nonobese CFS patients and nonobese 21 age-and gender-matched healthy controls. We investigated GH, ACTH and cortisol responses to insulin-induced hypoglycaemia. In a subgroup of patients arginine and clonidine stimulation for GH was also performed. Nocturnal secretion of GH, ACTH and cortisol were determined. Serum levels of IGF-I, prolactin, TSH, and free thyroxine were also measured. Visceral fat mass was assessed by CT scanning. GH response to insulin induced hypoglycaemia assessed by peak value (17.0 +/- 13.1 microg/l vs. 22. 1 +/- 9.8 microg/l; P = 0.01) and by AUC (450.0 +/- 361.3 microg/l vs. 672.3 +/- 393.0 microg/l; P = 0.002) was significantly decreased in CFS patients vs. controls. Nocturnal GH secretion assessed by GH peak value (5.4 +/- 3.7 vs. 9.0 +/- 5.1 microg/l; P = 0.44) and by AUC (34.4 +/- 20.2 vs. 67.4 +/- 43.1; P = 0.045) was also significantly impaired in CFS patients. Arginine and clonidine administration showed no differences in GH secretion between CFS patients and controls. In the CFS group, GH peak values were significantly higher after ITT than after arginine (P = 0.017) or clonidine (P = 0.001). No differences in serum IGF-I levels were found between CFS patients and controls. Except for a significantly lower nocturnal cortisol peak value, no differences were found in ACTH and cortisol secretion between CFS patients and controls. Significantly higher serum prolactin levels (7.4 +/- 4.7 microg/l vs. 4.4 +/- 1.3 microg/l; P = 0.004) and significantly higher serum

Cooperative Secret Sharing Using QR Codes and Symmetric Keys

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Yang-Wai Chow

2018-04-01

Full Text Available Secret sharing is an information security technique where a dealer divides a secret into a collection of shares and distributes these to members of a group. The secret will only be revealed when a predefined number of group members cooperate to recover the secret. The purpose of this study is to investigate a method of distributing shares by embedding them into cover Quick Response (QR codes in a secure manner using cryptographic keys. The advantage of this approach is that the shares can be disseminated over public channels, as anyone who scans the QR codes will only obtain public information. Only authorized individuals who are in possession of the required keys will be able to recover the shares. This also means that when group members cooperate to recover a secret, the group can determine the presence of an illegitimate participant if the person does not produce a valid share. This study proposes a protocol for accomplishing this and discusses the underlying security of the protocol.

Meaningful Share Generation for Increased Number of Secrets in Visual Secret-Sharing Scheme

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Mustafa Ulutas

2010-01-01

Full Text Available This paper presents a new scheme for hiding two halftone secret images into two meaningful shares created from halftone cover images. Meaningful shares are more desirable than noise-like (meaningless shares in Visual Secret Sharing because they look natural and do not attract eavesdroppers' attention. Previous works in the field focus on either increasing number of secrets or creating meaningful shares for one secret image. The method outlined in this paper both increases the number of secrets and creates meaningful shares at the same time. While the contrast ratio of shares is equal to that of Extended Visual Cryptography, two secrets are encoded into two shares as opposed to one secret in the Extended Visual Cryptography. Any two natural-looking images can be used as cover unlike the Halftone Visual Cryptography method where one cover should be the negative of the other cover image and can only encode one secret. Effectiveness of the proposed method is verified by an experiment.

Pathogenic characteristics of yeasts isolated from vaginal secretion preserved under mineral oil

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B Severo Gomes

2011-01-01

Full Text Available In order to evaluate the pathogenicity of yeasts isolated from vaginal secretion of pregnant and non-pregnant women - stored in mineral oil at the URM Mycology Collection, Department of Mycology, Federal University of Pernambuco - 30 samples belonging to the genera Candida, Rhodotorula, Trichosporon, and Kloeckera, were studied regarding their pathogenic characteristics, ability to grow at room temperature (28°C ± 1°C, 37°C, and 42°C for 72 hours, and production of both phospholipase and proteinase. Results showed that all 30 isolates (100% were able to grow at room temperature and 37°C, and that 17 samples (57% were able to grow at 42°C. Evaluation of enzymatic activity showed protease activity in only two isolates (7%, namely C. maritima and C. obtusa. Phospholipase activity was detected in 20 isolates (67% using soy lecithin as substrate at different temperatures. The characterization of yeasts isolated from vaginal secretion and determination of their enzymatic activity may contribute to understanding the epidemiology of vulvovaginitis and assist in the treatment of patients.

Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Glintborg, Dorte; Hermann, Anne Pernille; Andersen, Marianne

2006-01-01

OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study. ......, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment....

Ectosomes: a new mechanism for non-exosomal secretion of tau protein.

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Simon Dujardin

Full Text Available Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested that Tau may be secreted and play a role in neural network signalling. However, once deregulated, secreted Tau may also participate in the spreading of Tau pathology in hierarchical pathways of neurodegeneration. The mechanisms underlying neuron-to-neuron Tau transfer are still unknown; given the known role of extra-cellular vesicles in cell-to-cell communication, we wondered whether these vesicles could carry secreted Tau. We found, among vesicles, that Tau is predominately secreted in ectosomes, which are plasma membrane-originating vesicles, and when it accumulates, the exosomal pathway is activated.

Reduced CX3CL1 secretion contributes to the susceptibility of oral leukoplakia-associated fibroblasts to Candida albicans

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Ran Cheng

2016-11-01

Full Text Available Candida leukoplakia (OLK is a kind of oral leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK. However, little is known about the etiology, including susceptibility of leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial peptides secreted by oral epithelial cells or fibroblasts potentially have antifungal activities against Candida albicans (C. albicans. In this study, we established three co-culture models to simulate different C. albicans-fibroblasts interactions during progression of candida leukoplakia. The susceptibility of oral leukoplakia-associated fibroblasts (LKAFs to C. albicans and its underlying mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs were collected. The co-culture models showed that LKAFs had promoted the adhesion, invasion, and survival of C. albicans compared with NFs. CX3CL1, a chemokine with antifungal activity, was less abundant in LKAFs than NFs. Overexpression of CX3CL1 via transfection in LKAFs could partly restore the resistance to C. albicans. We also showed that inhibition of ERK could suppress CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs. Besides, the expression of a shedding enzyme for CX3CL1, disintegrin and metalloproteinase domain (ADAM 17 was decreased in LKAFs than NFs. In conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK signaling pathway, thereby contributing to impaired cell resistance to C. albicans.

[Functional impairment and radiologic fasciitis under erlotinib therapy].

Science.gov (United States)

Osdoit, S; Wierzbicka, E; Guillet, G

2011-01-01

Targeted molecules are recent and valuable weapons in the management of certain cancers. Among them, erlotinib is an inhibitor of epidermal growth factor receptor approved in non-small lung cancer and pancreatic cancer after failure of first line treatment. Erlotinib is responsible for many cutaneous side effects. We report a case of acute symptomatic fasciitis that has occurred during erlotinib therapy. To our knowledge it is the first case described. A 56-year-old man was treated with erlotinib for a metastatic non-small lung adenocarcinoma. Shortly after the treatment by erlotinib was introduced, he had a severe acneiform rash resistant to doxycycline treatment. After a year of treatment, he presented intense pain in the legs with functional impairment. Medical imaging confirmed fasciitis. It regressed along with the rash after using strong topical corticosteroids during ten days. Besides bacterial fasciitis, inflammatory and oedematous fasciitis have varied aetiologies. The occurrence of a documented fasciitis during anti EGFR-therapy is original and raises the question of underlying mechanism. We suggest three pathophysiological mechanisms: spreading by contiguity; paraneoplastic fasciitis, or specific lesion of the fascia due to anti-EGFR. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Sleep disturbances and memory impairment among pregnant women consuming khat: An under-recognized problem

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Md. Dilshad Manzar

2017-01-01

Full Text Available Khat (Catha edulis is a evergreen flowering shrub that is cultivated at high altitudes, especially in East Africa and the southwest of the Arabian Peninsula. The plant contains alkaloids, of which cathinone and cathine have structural similarity and pharmacological action similar to amphetamines. The leaves are, therefore, consumed in some regions as a psychoactive stimulant due to cultural beliefs and misperceptions on the health benefits of khat consumption. This resulted in a growing prevalence of khat consumption among pregnant women. The myriad of physiological changes associated with pregnancy impairs sleep and memory. Moreover, khat has also been shown to have adverse effects on memory and sleep. Therefore, its use during pregnancy may further aggravate those impairments. The purpose of this mini-review is to summarize the changes in sleep and memory during pregnancy and the evidence supporting a relationship between khat consumption and neurocognitive deficits and sleep dysfunctions. The misperceptions of beneficial effects of khat, the high prevalence of consumption among pregnant women, and the possibility of under-reporting of khat abuse do necessitate the development of alternative methodologies to identify cases of unreported khat abuse in pregnant women. It is proposed that screening for sleep problems and memory deficits may help identify under-reported cases of khat abuse in pregnant women.

Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.

Science.gov (United States)

Limesand, Sean W; Rozance, Paul J

2017-08-01

Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Huperzine A, but not tacrine, stimulates S100B secretion in astrocyte cultures.

Science.gov (United States)

Lunardi, Paula; Nardin, Patrícia; Guerra, Maria Cristina; Abib, Renata; Leite, Marina Concli; Gonçalves, Carlos-Alberto

2013-04-09

The loss of cholinergic function in the central nervous system contributes significantly to the cognitive decline associated with advanced age and dementias. Huperzine A (HupA) is a selective inhibitor of acetylcholinesterase (AChE) and has been shown to significantly reduce cognitive impairment in animal models of dementia. Based on the importance of astrocytes in physiological and pathological brain activities, we investigated the effect of HupA and tacrine on S100B secretion in primary astrocyte cultures. S100B is an astrocyte-derived protein that has been proposed to be a marker of brain injury. Primary astrocyte cultures were exposed to HupA, tacrine, cholinergic agonists, and S100B secretion was measured by enzyme-linked immunosorbent assay (ELISA) at 1 and 24h. HupA, but not tacrine, at 100μM significantly increased S100B secretion in astrocyte cultures. Nicotine (at 100 and 1000μM) was able to stimulate S100B secretion in astrocyte cultures. Our data reinforce the idea that AChE inhibitors, particularly HupA, do not act exclusively on the acetylcholine balance. This effect of HupA could contribute to improve the cognitive deficit observed in patients, which are attributed to cholinergic dysfunction. In addition, for the first time, to our knowledge, these data indicate that S100B secretion can be modulated by nicotinic receptors, in addition to glutamate, dopamine and serotonin receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

Unconventional Protein Secretion in Animal Cells.

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Ng, Fanny; Tang, Bor Luen

2016-01-01

All eukaryotic cells secrete a range of proteins in a constitutive or regulated manner through the conventional or canonical exocytic/secretory pathway characterized by vesicular traffic from the endoplasmic reticulum, through the Golgi apparatus, and towards the plasma membrane. However, a number of proteins are secreted in an unconventional manner, which are insensitive to inhibitors of conventional exocytosis and use a route that bypasses the Golgi apparatus. These include cytosolic proteins such as fibroblast growth factor 2 (FGF2) and interleukin-1β (IL-1β), and membrane proteins that are known to also traverse to the plasma membrane by a conventional process of exocytosis, such as α integrin and the cystic fibrosis transmembrane conductor (CFTR). Mechanisms underlying unconventional protein secretion (UPS) are actively being analyzed and deciphered, and these range from an unusual form of plasma membrane translocation to vesicular processes involving the generation of exosomes and other extracellular microvesicles. In this chapter, we provide an overview on what is currently known about UPS in animal cells.

Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes

DEFF Research Database (Denmark)

Nauck, M A; Vardarli, I; Deacon, C F

2011-01-01

The incretin hormones gastric inhibitory polypeptide and especially glucagon-like peptide (GLP) have an important physiological function in augmenting postprandial insulin secretion. Since GLP-1 may play a role in the pathophysiology and treatment of type 2 diabetes, assessment of meal-related GLP......-1 secretory responses in type 2 diabetic patients vs healthy individuals is of great interest. A common view states that GLP-1 secretion in patients with type 2 diabetes is deficient and that this applies to a lesser degree in individuals with impaired glucose tolerance. Such a deficiency...... with and without diabetes after oral glucose and mixed meals. Our analysis does not support the contention of a generalised defect in nutrient-related GLP-1 secretory responses in type 2 diabetes patients. Rather, factors are identified that may determine individual incretin secretory responses and explain some...

Selective Impairment of Auditory Selective Attention under Concurrent Cognitive Load

Science.gov (United States)

Dittrich, Kerstin; Stahl, Christoph

2012-01-01

Load theory predicts that concurrent cognitive load impairs selective attention. For visual stimuli, it has been shown that this impairment can be selective: Distraction was specifically increased when the stimulus material used in the cognitive load task matches that of the selective attention task. Here, we report four experiments that…

Impaired glucose-induced glucagon suppression after partial pancreatectomy

DEFF Research Database (Denmark)

Schrader, Henning; Menge, Bjoern A; Breuer, Thomas G K

2009-01-01

INTRODUCTION: The glucose-induced decline in glucagon levels is often lost in patients with type 2 diabetes. It is unclear whether this is due to an independent defect in alpha-cell function or secondary to the impairment in insulin secretion. We examined whether a partial pancreatectomy in humans...... would also impair postchallenge glucagon concentrations and, if so, whether this could be attributed to the reduction in insulin levels. PATIENTS AND METHODS: Thirty-six patients with pancreatic tumours or chronic pancreatitis were studied before and after approximately 50% pancreatectomy with a 240-min...... oral glucose challenge, and the plasma concentrations of glucose, insulin, C-peptide, and glucagon were determined. RESULTS: Fasting and postchallenge insulin and C-peptide levels were significantly lower after partial pancreatectomy (P

Insulin sensitivity and secretion in Arab Americans with glucose intolerance.

Science.gov (United States)

Salinitri, Francine D; Pinelli, Nicole R; Martin, Emily T; Jaber, Linda A

2013-12-01

This study examined the pathophysiological abnormalities in Arab Americans with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of insulin secretion (HOMA-%β), and the Matsuda Insulin Sensitivity Index composite (ISIcomposite) were calculated from the fasting and stimulated glucose and insulin concentrations measured during the oral glucose tolerance test in a population-based, representative, cross-sectional sample of randomly selected Arab Americans. In total, 497 individuals (42±14 years old; 40% males; body mass index [BMI], 29±6 kg/m(2)) were studied. Multivariate linear regression models were performed to compare HOMA-IR, HOMA-%β, and ISIcomposite among individuals with normal glucose tolerance (NGT) (n=191) versus isolated IFG (n=136), isolated IGT (n=22), combined IFG/IGT (n=43), and diabetes (n=105). Compared with individuals with NGT (2.9±1.6), HOMA-IR progressively increased in individuals with isolated IFG (4.8±2.7, Psex and BMI, these associations remained unchanged. Whole-body insulin sensitivity as measured by ISIcomposite was significantly lower in individuals with isolated IFG (3.9±2.3, Psex, and BMI, isolated IFG (146.6±80.2) was also significantly associated with a decline in HOMA-%β relative to NGT (P=0.005). This study suggests that differences in the underlying metabolic defects leading to diabetes in Arab Americans with IFG and/or IGT exist and may require different strategies for the prevention of diabetes.

Growth hormone-secreting pituitary adenoma:clinical and MR imaging findings

International Nuclear Information System (INIS)

Park, Hong Suk; Chang, Kee Hyun; Han, Moon Hee; Sim, Jung Suk; Lee, Sang Hyun; Song, Jae Uoo; Yoo, In Kyu; Jung, Hee Won; Yeon, Kyung Mo

1996-01-01

To describe clinical and MRI findings of growth hormone-secreting pituitary adenoma, to determine if there are any characteristic MRI findings different from those of other pituitary adenomas, to evaluate the relationship between tumor size and serum growth hormone level, and to assess the results of immunohi-stochemical study. We retrospectively analysed clinical and MRI findings of 29 patients with growth hormone-secreting pituitary adenoma confirmed by serum growth hormone level and surgery. We also evaluated the relationship between the tumor volume and serum growth hormone level, and the results of immunohistochemical study. Coronal and sagittal T1-weighted MR images in all patients and gadolinium-enhanced T1-weighted MR images in 28 patients were obtained with 2.0 T(24 cases) and 0.5 T(5 cases) MR imagers. The images were analyzed in terms of tumor size, signal intensity, degree of contrast enhancement, extent of tumor growth and the presence or absence of cystic change, hemorrhage and calcification. Clinical manifestations included facial feature change and soft tissue swelling of hands and feet(n=29), headache(n=12), impaired visual acuity(n=9), symptoms of hyperprolactinemia(n=8), visual field defect(n=5), and others(n=6). On MR images, all of the 29 cases were seen to be macroadenomas and the size of the tumors averaged 2.2cm(1-5.2cm). Supra- and infrasellar extensions were seen in 21 and 22 patients, respectively. Cavernous sinus invasion was noted in seven, and in one this was bilateral. Signal intensity was isointense with cortical grey matter in 26 cases(90%). Cystic change or necrosis was seen in eight cases(28%), hemorrhage in four(14%), and calcification in two(7%). After enhancement, most(25/28) of the tumors enhanced less than normal pituitary in degree. There was no correlation between serum growth hormone level and tumor size. Immunohistochemical study showed positive growth hormone-secreting pituitary adenomas were various and included

Growth hormone-secreting pituitary adenoma:clinical and MR imaging findings

Energy Technology Data Exchange (ETDEWEB)

Park, Hong Suk; Chang, Kee Hyun; Han, Moon Hee; Sim, Jung Suk; Lee, Sang Hyun; Song, Jae Uoo; Yoo, In Kyu; Jung, Hee Won; Yeon, Kyung Mo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

1996-10-01

To describe clinical and MRI findings of growth hormone-secreting pituitary adenoma, to determine if there are any characteristic MRI findings different from those of other pituitary adenomas, to evaluate the relationship between tumor size and serum growth hormone level, and to assess the results of immunohi-stochemical study. We retrospectively analysed clinical and MRI findings of 29 patients with growth hormone-secreting pituitary adenoma confirmed by serum growth hormone level and surgery. We also evaluated the relationship between the tumor volume and serum growth hormone level, and the results of immunohistochemical study. Coronal and sagittal T1-weighted MR images in all patients and gadolinium-enhanced T1-weighted MR images in 28 patients were obtained with 2.0 T(24 cases) and 0.5 T(5 cases) MR imagers. The images were analyzed in terms of tumor size, signal intensity, degree of contrast enhancement, extent of tumor growth and the presence or absence of cystic change, hemorrhage and calcification. Clinical manifestations included facial feature change and soft tissue swelling of hands and feet(n=29), headache(n=12), impaired visual acuity(n=9), symptoms of hyperprolactinemia(n=8), visual field defect(n=5), and others(n=6). On MR images, all of the 29 cases were seen to be macroadenomas and the size of the tumors averaged 2.2cm(1-5.2cm). Supra- and infrasellar extensions were seen in 21 and 22 patients, respectively. Cavernous sinus invasion was noted in seven, and in one this was bilateral. Signal intensity was isointense with cortical grey matter in 26 cases(90%). Cystic change or necrosis was seen in eight cases(28%), hemorrhage in four(14%), and calcification in two(7%). After enhancement, most(25/28) of the tumors enhanced less than normal pituitary in degree. There was no correlation between serum growth hormone level and tumor size. Immunohistochemical study showed positive growth hormone-secreting pituitary adenomas were various and included

Tubulin Polymerization-promoting Protein (TPPP/p25α) Promotes Unconventional Secretion of α-Synuclein through Exophagy by Impairing Autophagosome-Lysosome Fusion

DEFF Research Database (Denmark)

Ejlerskov, Patrick; Rasmussen, Izabela; Nielsen, Troels Tolstrup

2013-01-01

increase in the basal level of α-synuclein secreted into the medium. Secretion was strictly dependent on autophagy and could be up-regulated (trehalose and Rab1A) or down-regulated (3-methyladenine and ATG5 shRNA) by enhancers or inhibitors of autophagy or by modulating minus-end-directed (HDAC6 sh...

37 CFR 10.57 - Preservation of confidences and secrets of a client.

Science.gov (United States)

2010-07-01

... and secrets of a client. 10.57 Section 10.57 Patents, Trademarks, and Copyrights UNITED STATES PATENT... confidences and secrets of a client. (a) “Confidence” refers to information protected by the attorney-client or agent-client privilege under applicable law. “Secret” refers to other information gained in the...

Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

DEFF Research Database (Denmark)

Schmidt, P T; Hansen, L; Hilsted, L

2004-01-01

BACKGROUND: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin....... METHODS: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. RESULTS: CCK infusion...... at 10(-9) M and 10(-8) M decreased gastrin output to 70.5% +/- 7.6% (n = 8) and 76.3% +/- 3.6% (n = 7) of basal output, respectively. CCK at 10(-10) M had no effect (n = 6). Somatostatin secretion was dose-dependently increased by CCK infusion and increased to 268 +/- 38.2% (n = 7) of basal secretion...

Secretion of human epidermal growth factor (EGF) in autotrophic culture by a recombinant hydrogen-utilizing bacterium, Pseudomonas pseudoflava, carrying broad-host-range EGF secretion vector pKSEGF2.

OpenAIRE

Hayase, N; Ishiyama, A; Niwano, M

1994-01-01

We constructed the broad-host-range human epidermal growth factor (EGF) secretion plasmid pKSEGF2 by inserting the Escherichia coli tac promoter, the signal sequence of Pseudomonas stutzeri amylase, and the synthesized EGF gene into the broad-host-range vector pKT230. E. coli JM109 carrying pKSEGF2 secreted EGF into the periplasm and the culture medium under the control of the tac promoter. Pseudomonas aeruginosa PAO1161 carrying pKSEGF2 and Pseudomonas putida AC10 carrying pKSEGF2 secreted E...

Dynamic quantum secret sharing

International Nuclear Information System (INIS)

Jia, Heng-Yue; Wen, Qiao-Yan; Gao, Fei; Qin, Su-Juan; Guo, Fen-Zhuo

2012-01-01

In this Letter we consider quantum secret sharing (QSS) between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications. -- Highlights: ► We consider quantum secret sharing between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). ► In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. ► Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. ► Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. ► Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications.

Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGFβ1-induced macrophages

International Nuclear Information System (INIS)

Machado, Camila Maria Longo; Andrade, Luciana Nogueira Sousa; Teixeira, Verônica Rodrigues; Costa, Fabrício Falconi; Melo, Camila Morais; Santos, Sofia Nascimento dos; Nonogaki, Suely; Liu, Fu-Tong; Bernardes, Emerson Soares; Camargo, Anamaria Aranha; Chammas, Roger

2014-01-01

In order to study the role of galectin-3 in tumor angiogenesis associated with tumor-associated macrophages (TAM) and tumor parenchyma, the galectin-3 expression was reconstituted in Tm1 melanoma cell line that lacks this protein. Galectin-3-expressing cells (Tm1G3) and mock-vector transfected cells (Tm1N3) were injected into wild-type (WT) and galectin-3 knockout (KO) C57Bl/6 mice. Tumors originated from Tm1G3 were larger in tumor volume with enlarged functional vessels, decreased necrotic areas, and increased vascular endothelial growth factor (VEGF) protein levels. Galectin-3-nonexpressing-cells injected into WT and KO showed increased levels of transforming growth factor beta 1 (TGFβ1) and, in WT animals this feature was also accompanied by increased VEGFR2 expression and its phosphorylation. In KO animals, tumors derived from galectin-3-expressing cells were infiltrated by CD68 + -cells, whereas in tumors derived from galectin-3-nonexpressing-cells, CD68 + cells failed to infiltrate tumors and accumulated in the periphery of the tumor mass. In vitro studies showed that Tm1G3 secreted more VEGF than Tm1N3 cells. In the latter case, TGFβ1 induced VEGF production. Basal secretion of VEGF was higher in WT-bone marrow-derived macrophages (BMDM) than in KO-BMDM. TGFβ1 induced secretion of VEGF only in WT-BMDM. Tm1G3-induced tumors had the Arginase I mRNA increased, which upregulated alternative macrophage (M2)/TAM induction. M2 stimuli, such as interleukin-4 (IL4) and TGFβ1, increased Arginase I protein levels and galectin-3 expression in WT- BMDM, but not in cells from KO mice. Hence, we report that galectin-3 disruption in tumor stroma and parenchyma decreases angiogenesis through interfering with the responses of macrophages to the interdependent VEGF and TGFβ1 signaling pathways

Effect of head x-irradiation on adrenal medullary secretion

International Nuclear Information System (INIS)

Mieno, Masahiro

1977-01-01

The purpose of the present experiments was to investigate an immediate effect of head x-irradiation on the secretion of adrenaline and noradrenaline by the adrenal medulla. When the dogs were irradiated with 200 or 800 R of x-rays to their heads under pentobarbital anesthesia, the majority of the animals showed no stimulation of the adrenal medulla but the minority showed a slight but definite increase in the secretion of adrenaline, the peak being attained within 60 min after exposure. (auth.)

In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability, and induce apoptosis in the GT1-1 neuronal cell line.

Science.gov (United States)

Pal, Lubna; Chu, Hsiao-Pai; Shu, Jun; Topalli, Ilir; Santoro, Nanette; Karkanias, George

2007-10-01

To evaluate for direct toxic effects of high glucose concentrations on cellular physiology in GnRH secreting immortalized GT1-1 neurons. Prospective experimental design. In vitro experimental model using a cell culture system. GT1-1 cells were cultured in replicates in media with two different glucose concentrations (450 mg/dL and 100 mg/dL, respectively) for varying time intervals (24, 48, and 72 hours). Effects of glucose concentrations on GnRH secretion by the GT1-1 neurons were evaluated using a static culture model. Cell viability, cellular apoptosis, and cell cycle events in GT1-1 neurons maintained in two different glucose concentrations were assessed by flow cytometry (fluorescence-activated cell sorter) using Annexin V-PI staining. Adverse influences of high glucose concentrations on GnRH secretion and cell viability were noted in cultures maintained in high glucose concentration (450 mg/dL) culture medium for varying time intervals. A significantly higher percentage of cells maintained in high glucose concentration medium demonstrated evidence of apoptosis by a fluorescence-activated cell sorter. We provide in vitro evidence of glucose-induced cellular toxicity in GnRH secreting GT1-1 neurons. Significant alterations in GnRH secretion, reduced cell viability, and a higher percentage of apoptotic cells were observed in GT1-1 cells maintained in high (450 mg/dL) compared with low (100 mg/dL) glucose concentration culture medium.

[Poststroke cognitive, emotional impairment and sleep quality: efficience of treatment with melaxen].

Science.gov (United States)

Kulesh, A A; Shestakov, V V

2014-01-01

To study melatonin secretion and its correlations with poststroke cognitive, emotional impairment and sleep quality in the acute period of stroke and to assess treatment efficacy of melaxen. We studied 96 patients with acute stroke. A battery of tests and scales for assessment of neurological deficit, neuropsychological status and emotional impairment was used. The night urinary level of 6-sulfatoxymelatonin was assessed. The relationship between 6-sulfatoxymelatonin and cognitive, emotional status and sleep parameters was analyzed. The level of 6-sulfatoxymelatonin was decreased in the night urine. Patients with dysexecutive poststroke cognitive impairment had higher level of 6-sulfatoxymelatonin and patients with dysmnestic and mixed cognitive impairment had lower level of 6-sulfatoxymelatonin in comparison with patients with normal cognitive functions. Melaxen improved cognitive function and sleep parameters, reduced the level of anxiety in the early recovery period of stroke. A role of chronobiological processes in the development of clinical signs of stroke in the aspect of cognitive impairment is discussed.

Oxygenation decreases elastin secretion from rat ductus arteriosus smooth muscle cells.

Science.gov (United States)

Kawakami, Shoji; Minamisawa, Susumu

2015-08-01

The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The oxygen concentration in the blood rises after birth, and in the DA this increase in oxygen concentration causes functional closure, which is induced by smooth muscle contraction. Previous studies have demonstrated that hypoxia and/or oxygenation affect vascular remodeling of various vessels. Therefore, we hypothesized that the rise in oxygen concentration would affect the vascular structure of the DA due to production of proteins secreted from DA smooth muscle cells (SMC). Liquid chromatography-tandem mass spectrometry was used to comprehensively investigate the secreted proteins in the supernatant of rat DA SMC harvested under hypoxic conditions (1% oxygen) or under normoxic conditions (21% oxygen). We found that the rise in oxygen concentration reduced the secretion of elastin from DA SMC. On reverse transcription-polymerase chain reaction, the expression of elastin mRNA was not significantly changed in DA SMC from hypoxic to normoxic conditions. Given that elastin forms internal elastic lamina and elastic fibers in the vascular muscle layers, and that a rise in oxygen concentration reduced the secretion of elastin, this suggests that the rise in blood oxygen concentration after birth reduces the secretion of elastin, and therefore may play a role in DA structural remodeling after birth. © 2015 Japan Pediatric Society.

Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat β-Cells*

Science.gov (United States)

Sabourin, Jessica; Le Gal, Loïc; Saurwein, Lisa; Haefliger, Jacques-Antoine; Raddatz, Eric; Allagnat, Florent

2015-01-01

Store-operated Ca2+ channels (SOCs) are voltage-independent Ca2+ channels activated upon depletion of the endoplasmic reticulum Ca2+ stores. Early studies suggest the contribution of such channels to Ca2+ homeostasis in insulin-secreting pancreatic β-cells. However, their composition and contribution to glucose-stimulated insulin secretion (GSIS) remains unclear. In this study, endoplasmic reticulum Ca2+ depletion triggered by acetylcholine (ACh) or thapsigargin stimulated the formation of a ternary complex composed of Orai1, TRPC1, and STIM1, the key proteins involved in the formation of SOCs. Ca2+ imaging further revealed that Orai1 and TRPC1 are required to form functional SOCs and that these channels are activated by STIM1 in response to thapsigargin or ACh. Pharmacological SOCs inhibition or dominant negative blockade of Orai1 or TRPC1 using the specific pore mutants Orai1-E106D and TRPC1-F562A impaired GSIS in rat β-cells and fully blocked the potentiating effect of ACh on secretion. In contrast, pharmacological or dominant negative blockade of TRPC3 had no effect on extracellular Ca2+ entry and GSIS. Finally, we observed that prolonged exposure to supraphysiological glucose concentration impaired SOCs function without altering the expression levels of STIM1, Orai1, and TRPC1. We conclude that Orai1 and TRPC1, which form SOCs regulated by STIM1, play a key role in the effect of ACh on GSIS, a process that may be impaired in type 2 diabetes. PMID:26494622

Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.

Science.gov (United States)

Almuraikhy, Shamma; Kafienah, Wael; Bashah, Moataz; Diboun, Ilhame; Jaganjac, Morana; Al-Khelaifi, Fatima; Abdesselem, Houari; Mazloum, Nayef A; Alsayrafi, Mohammed; Mohamed-Ali, Vidya; Elrayess, Mohamed A

2016-11-01

A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated. Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application. Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group. Obesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.

Sympathetic arousal, but not disturbed executive functioning, mediates the impairment of cognitive flexibility under stress.

Science.gov (United States)

Marko, Martin; Riečanský, Igor

2018-05-01

Cognitive flexibility emerges from an interplay of multiple cognitive systems, of which lexical-semantic and executive are thought to be the most important. Yet this has not been addressed by previous studies demonstrating that such forms of flexible thought deteriorate under stress. Motivated by these shortcomings, the present study evaluated several candidate mechanisms implied to mediate the impairing effects of stress on flexible thinking. Fifty-seven healthy adults were randomly assigned to psychosocial stress or control condition while assessed for performance on cognitive flexibility, working memory capacity, semantic fluency, and self-reported cognitive interference. Stress response was indicated by changes in skin conductance, hearth rate, and state anxiety. Our analyses showed that acute stress impaired cognitive flexibility via a concomitant increase in sympathetic arousal, while this mediator was positively associated with semantic fluency. Stress also decreased working memory capacity, which was partially mediated by elevated cognitive interference, but neither of these two measures were associated with cognitive flexibility or sympathetic arousal. Following these findings, we conclude that acute stress impairs cognitive flexibility via sympathetic arousal that modulates lexical-semantic and associative processes. In particular, the results indicate that stress-level of sympathetic activation may restrict the accessibility and integration of remote associates and bias the response competition towards prepotent and dominant ideas. Importantly, our results indicate that stress-induced impairments of cognitive flexibility and executive functions are mediated by distinct neurocognitive mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased de novo riboflavin synthesis and hydrolysis of FMN are involved in riboflavin secretion from Hyoscyamus albus hairy roots under iron deficiency

OpenAIRE

Higa, Ataru; Khandakar, Jebunnahar; Mori, Yuko; Kitamura, Yoshie

2012-01-01

Riboflavin secretion by Hyoscyamus albus hairy roots under Fe deficiency was examined to determine where riboflavin is produced and whether production occurs via an enhancement of riboflavin biosynthesis or a stimulation of flavin mononucleotide (FMN) hydrolysis. Confocal fluorescent microscopy showed that riboflavin was mainly localized in the epidermis and cortex of the root tip and, at the cellular level, in the apoplast. The expressions of three genes involved in the de novo biosynthesis ...

Aspergillus niger Secretes Citrate to Increase Iron Bioavailability

Science.gov (United States)

Odoni, Dorett I.; van Gaal, Merlijn P.; Schonewille, Tom; Tamayo-Ramos, Juan A.; Martins dos Santos, Vitor A. P.; Suarez-Diez, Maria; Schaap, Peter J.

2017-01-01

Aspergillus niger has an innate ability to secrete various organic acids, including citrate. The conditions required for A. niger citrate overproduction are well described, but the physiological reasons underlying extracellular citrate accumulation are not yet fully understood. One of the less understood culture conditions is the requirement of growth-limiting iron concentrations. While this has been attributed to iron-dependent citrate metabolizing enzymes, this straightforward relationship does not always hold true. Here, we show that an increase in citrate secretion under iron limited conditions is a physiological response consistent with a role of citrate as A. niger iron siderophore. We found that A. niger citrate secretion increases with decreasing amounts of iron added to the culture medium and, in contrast to previous findings, this response is independent of the nitrogen source. Differential transcriptomics analyses of the two A. niger mutants NW305 (gluconate non-producer) and NW186 (gluconate and oxalate non-producer) revealed up-regulation of the citrate biosynthesis gene citA under iron limited conditions compared to iron replete conditions. In addition, we show that A. niger can utilize Fe(III) citrate as iron source. Finally, we discuss our findings in the general context of the pH-dependency of A. niger organic acid production, offering an explanation, besides competition, for why A. niger organic acid production is a sequential process influenced by the external pH of the culture medium. PMID:28824560

Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus

DEFF Research Database (Denmark)

Vilsbøll, T; Krarup, T; Sonne, J

2003-01-01

in patients with diabetes mellitus. The aim of the present investigation was to investigate incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its dependence on the magnitude of the meal stimulus. Plasma concentrations of incretin hormones (total, reflecting secretion and intact...... subjects (22% P = 0.04) during the large meal, compared with the small meal, perhaps reflecting the increased incretin response. We conclude: 1) that a decreased GLP-1 secretion may contribute to impaired insulin secretion in type 2 diabetes mellitus, whereas GIP and GLP-1 secretion is normal in type 1......, reflecting potential action) were measured during two meal tests (260 kcal and 520 kcal) in eight type 1 diabetic patients, eight lean healthy subjects, eight obese type 2 diabetic patients, and eight obese healthy subjects. Both in diabetic patients and in healthy subjects, significant increases in GLP-1...

Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation.

Directory of Open Access Journals (Sweden)

Sawako Yoshina

Full Text Available ADAMTS9 is a metalloprotease that cleaves components of the extracellular matrix and is also implicated in transport from the endoplasmic reticulum (ER to the Golgi. It has been reported that an ADAMTS9 gene variant is associated with type 2 diabetes. The underlying pathology of type 2 diabetes is insulin resistance and beta-cell dysfunction. However, the molecular mechanisms underlying ADAMTS9 function in beta cells and peripheral tissues are unknown. We show that loss of C. elegans GON-1, an ADAMTS9 homolog, alters lifespan and dauer formation. GON-1 loss impairs secretion of proteins such as insulin orthologs and TGF-beta, and additionally impacts insulin/IGF-1 signaling in peripheral tissues. The function of the GON domain, but not the protease domain, is essential for normal lifespan and dauer formation in these scenarios. We conclude that the GON domain is critical for ADAMTS9/GON-1 function across species, which should help the understanding of type 2 diabetes in humans.

Systematic high-yield production of human secreted proteins in Escherichia coli

International Nuclear Information System (INIS)

Dai Xueyu; Chen Qiang; Lian Min; Zhou Yanfeng; Zhou Mo; Lu Shanyun; Chen Yunjia; Luo Jingchu; Gu Xiaocheng; Jiang Ying; Luo Ming; Zheng Xiaofeng

2005-01-01

Human secreted proteins play a very important role in signal transduction. In order to study all potential secreted proteins identified from the human genome sequence, systematic production of large amounts of biologically active secreted proteins is a prerequisite. We selected 25 novel genes as a trial case for establishing a reliable expression system to produce active human secreted proteins in Escherichia coli. Expression of proteins with or without signal peptides was examined and compared in E. coli strains. The results indicated that deletion of signal peptides, to a certain extent, can improve the expression of these proteins and their solubilities. More importantly, under expression conditions such as induction temperature, N-terminus fusion peptides need to be optimized in order to express adequate amounts of soluble proteins. These recombinant proteins were characterized as well-folded proteins. This system enables us to rapidly obtain soluble and highly purified human secreted proteins for further functional studies

The problem of using trade secrets in economic relations

Directory of Open Access Journals (Sweden)

А. О. Олефір

2015-05-01

Full Text Available Problem setting. In a market economy and increased competition between enterprises become increasingly important concepts such as business information, trade secrets, know-how, confidential information, the information with restricted access. Given the fact that only one patent protection is unable to meet the needs of researchers, in addition to formal public protection and secured legal means we would like to pay attention at private legal measures, particular, the mode of trade secrets. Recent research and publications analysis. Different aspects of the protection of trade secrets were investigated by specialists such as G. Androschuk, J. Berzhye, I. Davydov, O. Davydyuk, D. Zadyhaylo, P. Kraynov, G. Nikiforov, S. Nikiforov, V. Rubanov, E. Solovyov, L. Hoffman, V. Chaplygin, A. Cherniavsky and others. However, at present there is a lack of comprehensive research of this legal phenomenon, equally useful for innovators and businesses that actively protect corporate security. Paper objective. This article is planned to determine the legal characteristics, structural elements and mechanisms by which the use of trade secrets in business have a positive impact on innovation development and corporate security entities. Paper main body. On the basis of requirements of Art. 505 Civil Code of Ukraine and art. 39 of the TRIPS Agreement we formulated commercial information signs under which it receives legal protection as an object of intellectual property: (1 privacy (real or potential in the sense that it is as a whole or in a precise combination of aggregate and its components are not generally known or available to persons in the circles that normally deal with such information; (2 commercial value (not purely industrial or industrial, due to its secrecy; this information is unknown to others, which is a commercial interest; (3 the lawful holder of the information provides active special measures (technical, organizational, legal to preserve secrecy

Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients, but not in Helicobacter pylori positive healthy subjects

DEFF Research Database (Denmark)

A, Mertz-Nielsen; Hillingsø, Jens; Frøkiær, Hanne

1996-01-01

Background: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E(2) than healthy subjects. Our purpose was to determine whether this abnormality...... was present also in the stomach of DU patients. Methods: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE(2) were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H. pylori-positivr). Results: In healthy...... be responsible for the abnormally high gastric secretion of bicarbonate in inactive DU patients. Th; defective duodenal secretion of bicarbonate observed in these patients may be a consequence of previous ulceration rather than the mere presence of H. pylori infection....

Muscles Activity in the elderly with Balance Impairments in walking under Dual tasks

Directory of Open Access Journals (Sweden)

Elaheh Azadian

2016-09-01

Full Text Available Objectives: Each step during gait requires different attention demands that will affect muscles activity. The study of changes in the timing and intensity of the muscles activity in walking with dual task has received less attention from researchers. The purpose of this study was to evaluate changes in electromyography patterns of gait with cognitive dual tasks in balance impaired elderly. Methods: Thirty older adults were recruited for this study. People were selected through berg balance test. Subjects walked 12-meters in two conditions, normal walking and walking with a cognitive dual task. Spatial-temporal kinematic parameters were recorded through the motion analysis and muscles activities were recorded through electromyography system. The data obtained was analyzed using repeated measures ANOVA at a significant level of p< 0.05.  Results: The results showed that walking under dual tasks would decrease gait speed and increase stride time and stance time. Also muscle activity in Tibialis anterior and Vastus lateralis in stance-phase would decrease significantly in dual tasks as compared with single task (p< 0.05, but timing of muscle activity would not change in dual task conditions.  Conclusions: Based on the results, it can be argued that walking under a dual task can change spatial-temporal parameters and muscle activity in gait pattern in the elderly with balance impairment. One explanation could be that the decreased control of the central nervous system on muscle activity in stance phase due to the performing of a dual task.

Insulin Resistance and Impaired Pancreatic β-Cell Function in Adult Offspring of Women With Diabetes in Pregnancy

DEFF Research Database (Denmark)

Kelstrup, Louise; Damm, Peter; Mathiesen, Elisabeth R

2013-01-01

Context:Offspring of women with diabetes during pregnancy have increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate effects of intrauterine hyperglycemia on insulin secretion and - action in adult offspring of mothers...... a standard oral glucose tolerance test (120 minutes, 75 gram glucose). Pancreatic beta-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices.Results:Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes.......005).Conclusion:Reduced insulin sensitivity as well as impaired pancreatic beta cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy....

Role of aryl hydrocarbon receptor nuclear translocator in KATP channel-mediated insulin secretion in INS-1 insulinoma cells

International Nuclear Information System (INIS)

Kim, Ji-Seon; Zheng Haifeng; Kim, Sung Joon; Park, Jong-Wan; Park, Kyong Soo; Ho, Won-Kyung; Chun, Yang-Sook

2009-01-01

Aryl hydrocarbon receptor nuclear translocator (ARNT) has been known to participate in cellular responses to xenobiotic and hypoxic stresses, as a common partner of aryl hydrocarbon receptor and hypoxia inducible factor-1/2α. Recently, it was reported that ARNT is essential for adequate insulin secretion in response to glucose input and that its expression is downregulated in the pancreatic islets of diabetic patients. In the present study, the authors addressed the mechanism by which ARNT regulates insulin secretion in the INS-1 insulinoma cell line. In ARNT knock-down cells, basal insulin release was elevated, but insulin secretion was not further stimulated by a high-glucose challenge. Electrophysiological analyses revealed that glucose-dependent membrane depolarization was impaired in these cells. Furthermore, K ATP channel activity and expression were reduced. Of two K ATP channel subunits, Kir6.2 was found to be positively regulated by ARNT at the mRNA and protein levels. Based on these results, the authors suggest that ARNT expresses K ATP channel and by so doing regulates glucose-dependent insulin secretion.

Quantum strongly secure ramp secret sharing

DEFF Research Database (Denmark)

Zhang, Paul; Matsumoto, Rytaro Yamashita

2015-01-01

Quantum secret sharing is a scheme for encoding a quantum state (the secret) into multiple shares and distributing them among several participants. If a sufficient number of shares are put together, then the secret can be fully reconstructed. If an insufficient number of shares are put together...... however, no information about the secret can be revealed. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an unqualified set, that cannot fully reconstruct the secret. By allowing this, the size of a share can be drastically reduced....... This paper introduces a quantum analog of classical strong security in ramp secret sharing schemes. While the ramp secret sharing scheme still leaks partial information about the secret to unqualified sets of participants, the strong security condition ensures that qudits with critical information can...

The Diversity-Multiplexing Tradeoff of Secret-Key Agreement over Multiple-Antenna Channels

KAUST Repository

Zorgui, Marwen; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

2015-01-01

We study the problem of secret-key agreement between two legitimate parties, Alice and Bob, in presence an of eavesdropper Eve. There is a public channel with unlimited capacity that is available to the legitimate parties and is also observed by Eve. Our focus is on Rayleigh fading quasi-static channels. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge of their channels. We study the system in the high-power regime. First, we define the secret-key diversity gain and the secret-key multiplexing gain. Second, we establish the secret-key diversity multiplexing tradeoff (DMT) under no channel state information (CSI) at the transmitter (CSI-T). The eavesdropper is shown to “steal” only transmit antennas. We show that, likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information at the transmitter. This insensitivity of secret-key DMT toward CSI-T features a fundamental difference between secret-key agreement and the wiretap channel, in which secret DMT depends heavily on CSI-T. Finally, we present several secret-key DMT-achieving schemes in case of full CSI-T. We argue that secret DMT-achieving schemes are also key DMT-achieving. Moreover, we show formally that artificial noise (AN), likewise zero-forcing (ZF), is DMT-achieving. We also show that the public feedback channel improves the outage performance without having any effect on the DMT.

The Diversity-Multiplexing Tradeoff of Secret-Key Agreement over Multiple-Antenna Channels

KAUST Repository

Zorgui, Marwen

2015-10-26

We study the problem of secret-key agreement between two legitimate parties, Alice and Bob, in presence an of eavesdropper Eve. There is a public channel with unlimited capacity that is available to the legitimate parties and is also observed by Eve. Our focus is on Rayleigh fading quasi-static channels. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge of their channels. We study the system in the high-power regime. First, we define the secret-key diversity gain and the secret-key multiplexing gain. Second, we establish the secret-key diversity multiplexing tradeoff (DMT) under no channel state information (CSI) at the transmitter (CSI-T). The eavesdropper is shown to “steal” only transmit antennas. We show that, likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information at the transmitter. This insensitivity of secret-key DMT toward CSI-T features a fundamental difference between secret-key agreement and the wiretap channel, in which secret DMT depends heavily on CSI-T. Finally, we present several secret-key DMT-achieving schemes in case of full CSI-T. We argue that secret DMT-achieving schemes are also key DMT-achieving. Moreover, we show formally that artificial noise (AN), likewise zero-forcing (ZF), is DMT-achieving. We also show that the public feedback channel improves the outage performance without having any effect on the DMT.

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

Science.gov (United States)

Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

2013-01-01

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

FluG affects secretion in colonies of Aspergillus niger.

Science.gov (United States)

Wang, Fengfeng; Krijgsheld, Pauline; Hulsman, Marc; de Bekker, Charissa; Müller, Wally H; Reinders, Marcel; de Vries, Ronald P; Wösten, Han A B

2015-01-01

Colonies of Aspergillus niger are characterized by zonal heterogeneity in growth, sporulation, gene expression and secretion. For instance, the glucoamylase gene glaA is more highly expressed at the periphery of colonies when compared to the center. As a consequence, its encoded protein GlaA is mainly secreted at the outer part of the colony. Here, multiple copies of amyR were introduced in A. niger. Most transformants over-expressing this regulatory gene of amylolytic genes still displayed heterogeneous glaA expression and GlaA secretion. However, heterogeneity was abolished in transformant UU-A001.13 by expressing glaA and secreting GlaA throughout the mycelium. Sequencing the genome of UU-A001.13 revealed that transformation had been accompanied by deletion of part of the fluG gene and disrupting its 3' end by integration of a transformation vector. Inactivation of fluG in the wild-type background of A. niger also resulted in breakdown of starch under the whole colony. Asexual development of the ∆fluG strain was not affected, unlike what was previously shown in Aspergillus nidulans. Genes encoding proteins with a signal sequence for secretion, including part of the amylolytic genes, were more often downregulated in the central zone of maltose-grown ∆fluG colonies and upregulated in the intermediate part and periphery when compared to the wild-type. Together, these data indicate that FluG of A. niger is a repressor of secretion.

Impairment of Goodwill and Deferred Taxes under IFRS

NARCIS (Netherlands)

Detzen, D.; Stork-Wersborg, T.; Zulch, H.

2016-01-01

This article discusses the effect of deferred tax liabilities (DTLs) on an impairment test of goodwill. While IAS 12.66 acknowledges that DTLs arising in a business combination influence the amount of goodwill an entity recognises, International Financial Reporting Standards are silent on the

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

International Nuclear Information System (INIS)

Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

2015-01-01

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm 2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

2015-08-14

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

Lipopolysaccharide regulated protein expression is only partly impaired in monocytes from patients with type I diabetes

Directory of Open Access Journals (Sweden)

Abke Sabine

2006-03-01

Full Text Available Abstract Background Monocytes play an important role in innate immunity and atherosclerosis. A disturbed secretion of cytokines in lipopolysaccharide (LPS activated monocytes from type 1 diabetes (T1D patients has been described and may contribute to the impaired inflammatory response in these individuals. In the present study the influence of LPS on five different proteins with a function in immunity and atherosclerosis was analyzed in monocytes from controls and T1D patients. Methods Monocytes were isolated from controls and T1D patients and the LPS-stimulated increase of IL-6, CXCL8, monocyte chemotactic protein 1 (CCL2, MCP-1 and superoxide dismutase (SOD 2, as well as the LPS-mediated decrease of apolipoprotein E (Apo E in primary human monocytes from controls and T1D patients was determined. Results CCL2 and IL-6 secretion in response to LPS was found significantly reduced in monocytes from T1D patients when compared to controls whereas basal CCL2 release was similar in control and T1D cells. In contrast, CXCL8 and apolipoprotein E secretion and SOD 2 expression upon LPS stimulation is similar from T1D and control monocytes. Conclusion These data indicate that LPS-mediated protein expression is only partly disturbed in monocytes from T1D patients. Reduced secretion of IL-6 and CCL2 in activated monocytes of these patients may contribute to an impaired inflammatory response and vascular disease.

Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages.

Science.gov (United States)

Aflaki, Elma; Moaven, Nima; Borger, Daniel K; Lopez, Grisel; Westbroek, Wendy; Chae, Jae Jin; Marugan, Juan; Patnaik, Samarjit; Maniwang, Emerson; Gonzalez, Ashley N; Sidransky, Ellen

2016-02-01

Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylcer-amide macrophages, the accumulation of glucosylceramide in lysosomes and the secretion of inflammatory cytokines. However, the connection between this lysosomal storage and inflammation is not clear. Studying macrophages derived from peripheral monocytes from patients with type 1 Gaucher disease with genotype N370S/N370S, we confirmed an increased secretion of interleukins IL-1β and IL-6. In addition, we found that activation of the inflammasome, a multiprotein complex that activates caspase-1, led to the maturation of IL-1β in Gaucher macrophages. We show that inflammasome activation in these cells is the result of impaired autophagy. Treatment with the small-molecule glucocerebrosidase chaperone NCGC758 reversed these defects, inducing autophagy and reducing IL-1β secretion, confirming the role of the deficiency of lysosomal glucocerebrosidase in these processes. We found that in Gaucher macrophages elevated levels of the autophagic adaptor p62 prevented the delivery of inflammasomes to autophagosomes. This increase in p62 led to activation of p65-NF-kB in the nucleus, promoting the expression of inflammatory cytokines and the secretion of IL-1β. This newly elucidated mechanism ties lysosomal dysfunction to inflammasome activation, and may contribute to the massive organomegaly, bone involvement and increased susceptibility to certain malignancies seen in Gaucher disease. Moreover, this link between lysosomal storage, impaired autophagy, and inflammation may have implications relevant to both Parkinson disease and the aging process. Defects in these basic cellular processes may also provide new therapeutic targets. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dynamic secrets in communication security

CERN Document Server

Xiao, Sheng; Towsley, Donald

2013-01-01

Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

Ability of multicellular salt glands in Tamarix species to secrete Na+ and K+ selectively.

Science.gov (United States)

Ma, Haiyan; Tian, Changyan; Feng, Gu; Yuan, Junfeng

2011-03-01

The present study aimed to determine the mechanism of cation-selective secretion by multicellular salt glands. Using a hydroponic culture system, the secretion and accumulation of Na(+) and K(+) in Tamarix ramosissima and T. laxa under different salt stresses (NaCl, KCl and NaCl+KCl) were studied. Additionally, the effects of salt gland inhibitors (orthovanadate, Ba(2+), ouabain, tetraethylammonium (TEA) and verapamil) on Na(+) and K(+) secretion and accumulation were examined. Treatment with NaCl (at 0-200 mmol L(-1) levels) significantly increased Na(+) secretion, whereas KCl treatment (at 0-200 mmol L(-1) levels) significantly increased K(+) secretion. The ratio of secretion to accumulation of Na(+) was higher than that of K(+). The changes in Na(+) and K(+) secretion differed after adding different ions into the single-salt solutions. Addition of NaCl to the KCl solution (at 100 mmol L(-1) level, respectively) led to a significant decrease in K(+) secretion rate, whereas addition of KCl to the NaCl solution (at 100 mmol L(-1) level, respectively) had little impact on the Na(+) secretion rate. These results indicated that Na+ secretion in Tamarix was highly selective. In addition, Na(+) secretion was significantly inhibited by orthovanadate, ouabain, TEA and verapamil, and K(+) secretion was significantly inhibited by ouabain, TEA and verapamil. The different impacts of orthovanadate on Na(+) and K(+) secretion might be the primary cause for the different Na(+) and K(+) secretion abilities of multicellular salt glands in Tamarix.

The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing

DEFF Research Database (Denmark)

Luu, L; Dai, F F; Prentice, K J

2013-01-01

Sirtuin 1 (SIRT1) has emerged as a key metabolic regulator of glucose homeostasis and insulin secretion. Enhanced SIRT1 activity has been shown to be protective against diabetes, although the mechanisms remain largely unknown. The aim of this study was to determine how SIRT1 regulates insulin sec...

Narrative competence and underlying mechanisms in children with pragmatic language impairment

NARCIS (Netherlands)

Ketelaars, M.P.; Jansonius, K.; Cuperus, J.; Verhoeven, L.

2012-01-01

This study investigated narrative competence in children with pragmatic language impairment (PLI) and the extent to which it is related to impairments in theory of mind and executive functioning (EF). Narrative competence was assessed using a retelling design in a group of 77 children with PLI and a

Outcomes of percutaneous endoscopic gastrostomy tube insertion in respiratory impaired amyotrophic lateral sclerosis patients under noninvasive ventilation.

Science.gov (United States)

Czell, David; Bauer, Matthias; Binek, Janek; Schoch, Otto D; Weber, Markus

2013-05-01

Percutaneous endoscopic gastrostomy (PEG) tube placement in amyotrophic lateral sclerosis (ALS) patients with impaired respiratory function is associated with an increased risk of peri-procedural and post-interventional complications. It was the aim of the study to analyze peri- and post-interventional complications and survival after PEG tube placement under noninvasive ventilation (NIV) in ALS patients with various degrees of respiratory impairment. Twenty-six subjects were included in this retrospective case study. Prior to PEG tube placement, training with ventilatory support via an oronasal mask was performed with ALS subjects on the pneumology ward. PEG placement was then performed under continuous NIV. FVC, sniff nasal inspiratory pressure, and demographic data were assessed. Complication rates and 1-month and overall survival rates were analyzed. There were no deaths within 24 hours after PEG placement. One subject died within the first month. The mean survival rate after PEG was 12 ± 10 months (range 0.6-42 months). There was no difference in post-PEG survival between subjects with moderately (> 50%) and severely (NIV in ALS subjects.

Quantitative proteomic view on secreted, cell surface-associated, and cytoplasmic proteins of the methicillin-resistant human pathogen Staphylococcus aureus under iron-limited conditions.

Science.gov (United States)

Hempel, Kristina; Herbst, Florian-Alexander; Moche, Martin; Hecker, Michael; Becher, Dörte

2011-04-01

Staphylococcus aureus is capable of colonizing and infecting humans by its arsenal of surface-exposed and secreted proteins. Iron-limited conditions in mammalian body fluids serve as a major environmental signal to bacteria to express virulence determinants. Here we present a comprehensive, gel-free, and GeLC-MS/MS-based quantitative proteome profiling of S. aureus under this infection-relevant situation. (14)N(15)N metabolic labeling and three complementing approaches were combined for relative quantitative analyses of surface-associated proteins. The surface-exposed and secreted proteome profiling approaches comprise trypsin shaving, biotinylation, and precipitation of the supernatant. By analysis of the outer subproteomic and cytoplasmic protein fraction, 1210 proteins could be identified including 221 surface-associated proteins. Thus, access was enabled to 70% of the predicted cell wall-associated proteins, 80% of the predicted sortase substrates, two/thirds of lipoproteins and more than 50% of secreted and cytoplasmic proteins. For iron-deficiency, 158 surface-associated proteins were quantified. Twenty-nine proteins were found in altered amounts showing particularly surface-exposed proteins strongly induced, such as the iron-regulated surface determinant proteins IsdA, IsdB, IsdC and IsdD as well as lipid-anchored iron compound-binding proteins. The work presents a crucial subject for understanding S. aureus pathophysiology by the use of methods that allow quantitative surface proteome profiling.

Regulation of Pancreatic Beta Cell Stimulus-Secretion Coupling by microRNAs

Directory of Open Access Journals (Sweden)

Jonathan L. S. Esguerra

2014-11-01

Full Text Available Increased blood glucose after a meal is countered by the subsequent increased release of the hypoglycemic hormone insulin from the pancreatic beta cells. The cascade of molecular events encompassing the initial sensing and transport of glucose into the beta cell, culminating with the exocytosis of the insulin large dense core granules (LDCVs is termed “stimulus-secretion coupling.” Impairment in any of the relevant processes leads to insufficient insulin release, which contributes to the development of type 2 diabetes (T2D. The fate of the beta cell, when exposed to environmental triggers of the disease, is determined by the possibility to adapt to the new situation by regulation of gene expression. As established factors of post-transcriptional regulation, microRNAs (miRNAs are well-recognized mediators of beta cell plasticity and adaptation. Here, we put focus on the importance of comprehending the transcriptional regulation of miRNAs, and how miRNAs are implicated in stimulus-secretion coupling, specifically those influencing the late stages of insulin secretion. We suggest that efficient beta cell adaptation requires an optimal balance between transcriptional regulation of miRNAs themselves, and miRNA-dependent gene regulation. The increased knowledge of the beta cell transcriptional network inclusive of non-coding RNAs such as miRNAs is essential in identifying novel targets for the treatment of T2D.

Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study

DEFF Research Database (Denmark)

Gudmundsdottir, Valborg; Pedersen, Helle Krogh; Allebrandt, Karla Viviani

2018-01-01

Glucagon-like peptide 1 (GLP-1) stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS) of GLP-1 stimulated insulin...... secretion in non-diabetic individuals from the Netherlands Twin register (n = 126). This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS...... P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100). Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P

PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

DEFF Research Database (Denmark)

Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M

2013-01-01

by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate...

Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus

DEFF Research Database (Denmark)

Vilsbøll, Tina; Krarup, T; Sonne, J

2003-01-01

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones secreted in response to meal ingestion, thereby enhancing postprandial insulin secretion. Therefore, an attenuated incretin response could contribute to the impaired insulin responses...... with healthy subjects, whereas decreased GLP-1 responses were seen in type 2 diabetic patients, compared with matched obese healthy subjects. Incremental GLP-1 responses were normal in type 1 diabetic patients. Increased fasting concentrations of GIP and an early enhanced postprandial GIP response were seen...

Immunoglobins in mammary secretions

DEFF Research Database (Denmark)

Hurley, W L; Theil, Peter Kappel

2013-01-01

Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

Production, secretion, and stability of human secreted alkaline phosphatase in tobacco NT1 cell suspension cultures.

Science.gov (United States)

Becerra-Arteaga, Alejandro; Mason, Hugh S; Shuler, Michael L

2006-01-01

Tobacco NT1 cell suspension cultures secreting active human secreted alkaline phosphatase (SEAP) were generated for the first time as a model system to study recombinant protein production, secretion, and stability in plant cell cultures. The SEAP gene encodes a secreted form of the human placental alkaline phosphatase (PLAP). During batch culture, the highest level of active SEAP in the culture medium (0.4 U/mL, corresponding to approximately 27 mg/L) was observed at the end of the exponential growth phase. Although the level of active SEAP decreased during the stationary phase, the activity loss did not appear to be due to SEAP degradation (based on Western blots) but due to SEAP denaturation. The protein-stabilizing agents polyvinylpirrolidone (PVP) and bacitracin were added extracellularly to test for their ability to reduce the loss of SEAP activity during the stationary phase. Bacitracin (100 mg/L) was the most effective treatment at sustaining activity levels for up to 17 days post-subculture. Commercially available human placental alkaline phosphatase (PLAP) was used to probe the mechanism of SEAP deactivation. Experiments with PLAP in sterile and conditioned medium corroborated the denaturation of SEAP by factors generated by cell growth and not due to simple proteolysis. We also show for the first time that the factors promoting activity loss are heat labile at 95 degrees C but not at 70 degrees C, and they are not inactivated after a 5 day incubation period under normal culture conditions (27 degrees C). In addition, there were no significant changes in pH or redox potential when comparing sterile and cell-free conditioned medium during PLAP incubation, indicating that these factors were unimportant.

Matroids and quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Sarvepalli, Pradeep; Raussendorf, Robert

2010-01-01

A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previous work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.

Extracellular secretion of recombinant proteins

Science.gov (United States)

Linger, Jeffrey G.; Darzins, Aldis

2014-07-22

Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

Fluoride induces endoplasmic reticulum stress and inhibits protein synthesis and secretion.

Science.gov (United States)

Sharma, Ramaswamy; Tsuchiya, Masahiro; Bartlett, John D

2008-09-01

Exposure to excessive amounts of fluoride (F(-)) causes dental fluorosis in susceptible individuals; however, the mechanism of F(-)-induced toxicity is unclear. Previously, we have shown that high-dose F(-) activates the unfolded protein response (UPR) in ameloblasts that are responsible for dental enamel formation. The UPR is a signaling pathway responsible for either alleviating endoplasmic reticulum (ER) stress or for inducing apoptosis of the stressed cells. In this study we determined if low-dose F(-) causes ER stress and activates the UPR, and we also determined whether F(-) interferes with the secretion of proteins from the ER. We stably transfected the ameloblast-derived LS8 cell line with secreted alkaline phosphatase (SEAP) and determined activity and localization of SEAP and F(-)-mediated induction of UPR proteins. Also, incisors from mice given drinking water containing various concentrations of F(-) were examined for eucaryotic initiation factor-2, subunit alpha (eIF2alpha) phosphorylation. We found that F(-) decreases the extracellular secretion of SEAP in a linear, dose-dependent manner. We also found a corresponding increase in the intracellular accumulation of SEAP after exposure to F(-). These changes are associated with the induction of UPR proteins such as the molecular chaperone BiP and phosphorylation of the UPR sensor PKR-like ER kinase, and its substrate, eIF2alpha. Importantly, F(-)-induced phosphorylation of eIF2alphawas confirmed in vivo. These data suggest that F(-) initiates an ER stress response in ameloblasts that interferes with protein synthesis and secretion. Consequently, ameloblast function during enamel development may be impaired, and this may culminate in dental fluorosis.

Physiological and Molecular Analysis of Aluminium-Induced Organic Acid Anion Secretion from Grain Amaranth (Amaranthus hypochondriacus L.) Roots

Science.gov (United States)

Fan, Wei; Xu, Jia-Meng; Lou, He-Qiang; Xiao, Chuan; Chen, Wei-Wei; Yang, Jian-Li

2016-01-01

Grain amaranth (Amaranthus hypochondriacus L.) is abundant in oxalate and can secrete oxalate under aluminium (Al) stress. However, the features of Al-induced secretion of organic acid anions (OA) and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH) together with quantitative real-time PCR (qRT-PCR) was used to identify up-regulated genes that are potentially involved in OA secretion. The results showed that grain amaranth roots secrete both oxalate and citrate in response to Al stress. The secretion pattern, however, differs between oxalate and citrate. Neither lanthanum chloride (La) nor cadmium chloride (Cd) induced OA secretion. A total of 84 genes were identified as up-regulated by Al, in which six genes were considered as being potentially involved in OA secretion. The expression pattern of a gene belonging to multidrug and toxic compound extrusion (MATE) family, AhMATE1, was in close agreement with that of citrate secretion. The expression of a gene encoding tonoplast dicarboxylate transporter and four genes encoding ATP-binding cassette transporters was differentially regulated by Al stress, but the expression pattern was not correlated well with that of oxalate secretion. Our results not only reveal the secretion pattern of oxalate and citrate from grain amaranth roots under Al stress, but also provide some genetic information that will be useful for further characterization of genes involved in Al toxicity and tolerance mechanisms. PMID:27144562

Physiological and Molecular Analysis of Aluminium-Induced Organic Acid Anion Secretion from Grain Amaranth (Amaranthus hypochondriacus L.) Roots.

Science.gov (United States)

Fan, Wei; Xu, Jia-Meng; Lou, He-Qiang; Xiao, Chuan; Chen, Wei-Wei; Yang, Jian-Li

2016-04-30

Grain amaranth (Amaranthus hypochondriacus L.) is abundant in oxalate and can secrete oxalate under aluminium (Al) stress. However, the features of Al-induced secretion of organic acid anions (OA) and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH) together with quantitative real-time PCR (qRT-PCR) was used to identify up-regulated genes that are potentially involved in OA secretion. The results showed that grain amaranth roots secrete both oxalate and citrate in response to Al stress. The secretion pattern, however, differs between oxalate and citrate. Neither lanthanum chloride (La) nor cadmium chloride (Cd) induced OA secretion. A total of 84 genes were identified as up-regulated by Al, in which six genes were considered as being potentially involved in OA secretion. The expression pattern of a gene belonging to multidrug and toxic compound extrusion (MATE) family, AhMATE1, was in close agreement with that of citrate secretion. The expression of a gene encoding tonoplast dicarboxylate transporter and four genes encoding ATP-binding cassette transporters was differentially regulated by Al stress, but the expression pattern was not correlated well with that of oxalate secretion. Our results not only reveal the secretion pattern of oxalate and citrate from grain amaranth roots under Al stress, but also provide some genetic information that will be useful for further characterization of genes involved in Al toxicity and tolerance mechanisms.

Physiological and Molecular Analysis of Aluminium-Induced Organic Acid Anion Secretion from Grain Amaranth (Amaranthus hypochondriacus L. Roots

Directory of Open Access Journals (Sweden)

Wei Fan

2016-04-01

Full Text Available Grain amaranth (Amaranthus hypochondriacus L. is abundant in oxalate and can secrete oxalate under aluminium (Al stress. However, the features of Al-induced secretion of organic acid anions (OA and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH together with quantitative real-time PCR (qRT-PCR was used to identify up-regulated genes that are potentially involved in OA secretion. The results showed that grain amaranth roots secrete both oxalate and citrate in response to Al stress. The secretion pattern, however, differs between oxalate and citrate. Neither lanthanum chloride (La nor cadmium chloride (Cd induced OA secretion. A total of 84 genes were identified as up-regulated by Al, in which six genes were considered as being potentially involved in OA secretion. The expression pattern of a gene belonging to multidrug and toxic compound extrusion (MATE family, AhMATE1, was in close agreement with that of citrate secretion. The expression of a gene encoding tonoplast dicarboxylate transporter and four genes encoding ATP-binding cassette transporters was differentially regulated by Al stress, but the expression pattern was not correlated well with that of oxalate secretion. Our results not only reveal the secretion pattern of oxalate and citrate from grain amaranth roots under Al stress, but also provide some genetic information that will be useful for further characterization of genes involved in Al toxicity and tolerance mechanisms.

Physical Impairment

Science.gov (United States)

Trewin, Shari

Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

36 CFR 902.51 - Records relating to matters that are required by Executive order to be kept secret.

Science.gov (United States)

2010-07-01

... that are required by Executive order to be kept secret. 902.51 Section 902.51 Parks, Forests, and... order to be kept secret. Records relating to matters that are specifically authorized under criteria established by an Executive order to be kept secret in the interest of national defense or foreign policy...

Pituitary-hormone secretion by thyrotropinomas.

Science.gov (United States)

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M; Biermasz, Nienke R; Smit, Jan W; Frolich, Marijke; Keenan, Daniel M; Veldhuis, Johannes D; Romijn, Johannes A

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

Competition of organic anions for furosemide and p-aminohippurate secretion in the rabbit

International Nuclear Information System (INIS)

Bidiville, J.; Roch-Ramel, F.

1986-01-01

The excretion of [ 14 C]- or [ 35 S]furosemide and [ 3 H]-p-aminohippurate (PAH) injected within 4 min into the left renal artery of rabbits was measured under brisk mannitol diuresis. The estimated rate of furosemide secretion during the first pass through the left kidney was lower than that of PAH when neither of the two transport processes were saturated: 7.9 and 12.9% of the total amounts injected were secreted per minute, respectively. Different competitive inhibitors were injected i.v. Probenecid (50 mg/kg) inhibited furosemide and PAH secretion by 95 and 80%, respectively. Pyrazinoate at plasma concentrations of 3 to 5 mM had no effect on either anion. Indomethacin (10 mg/kg) depressed furosemide secretion by 24% but had no effect on PAH secretion. PAH at a concentration of 9 to 17 mM in plasma depressed furosemide secretion by only 44 to 66%. Furosemide did not inhibit PAH secretion when infused into the left renal artery at a rate 5000 times higher than PAH. It was concluded that furosemide is secreted partly by the transport system secreting PAH, for which it had only a low affinity, and partly by a transport system for which indomethacin had some affinity. This latter transport system, in turn, differs from that secreting pyrazinoate. The furosemide-induced natriuresis, in both kidneys, was proportional to the urinary excretion rate of furosemide until the fractional excretion of Na+ reached an apparent maximum of 20 to 30%

Semiquantum secret sharing using entangled states

International Nuclear Information System (INIS)

Li Qin; Chan, W. H.; Long Dongyang

2010-01-01

Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but one of them cannot. The presented protocols are also shown to be secure against eavesdropping.

Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

DEFF Research Database (Denmark)

Øzbay, Aygen; Møller, Niels; Juhl, Claus

2012-01-01

and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses...... of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction...... of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development...

Probabilistic Infinite Secret Sharing

OpenAIRE

Csirmaz, László

2013-01-01

The study of probabilistic secret sharing schemes using arbitrary probability spaces and possibly infinite number of participants lets us investigate abstract properties of such schemes. It highlights important properties, explains why certain definitions work better than others, connects this topic to other branches of mathematics, and might yield new design paradigms. A probabilistic secret sharing scheme is a joint probability distribution of the shares and the secret together with a colle...

Cause of impaired carbohydrate metabolism in hyperthyroidism

International Nuclear Information System (INIS)

Foeldes, J.; Megyesi, K.; Koranyi, L.

1984-01-01

Hyperthyroidism (HT) affects glucose metabolism in various ways. The role of insulin, glucagon and growth-hormone (GH) was determined. After glucose loading the insulin response is weaker in HT than in euthyroid subjects. Enhanced degradation of insulin has been reported. It is suggested that in HT the serum insulin concentration declines at a slightly accelerated rate. In HT the deranged carbohydrate metabolism might be a consequence of altered tissue sensitivity to insulin. To elucidate this problem insulin receptors on erythrocytes obtained from hyperthyroid women were investigated. The maximal specific binding of 125 I-insulin to RBC of hyperthyroid patients was decreased and the analysis refers to a decreased receptor concentration in RBC. The nature of glucagon secretion and its influence on glucose metabolism in HT was investigated. The basal plasma glucagon is elevated in hyperthyroid patients. The suppression of glucagon secretion induced by an oral glucose loading was of significantly lesser degree in hyperthyroid patients than in controls. Applying the erythrocyte receptor assay a decreased specific binding of 125 I-glucagon to RBC of hyperthyroid patients has been found and data indicate a significantly less glucagon receptor concentration in thyrotoxicosis. Physiological elevations of serum GH levels led to a significant impairment of glucose metabolism. Beside the GH-RH and somatostatin, the dopaminergic neurotransmitter system participates in the regulation of GH secretion too. It has been demonstrated that after administration of the dopamine agonist l-dopa the GH response was weaker in HT than in controls. This indicates that in thyrotoxicosis the GH secretion can not be stimulated in such a degree as in euthyroidism. (author)

Cause of impaired carbohydrate metabolism in hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

Foeldes, J.; Megyesi, K.; Koranyi, L. (Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary))

1984-01-01

Hyperthyroidism (HT) affects glucose metabolism in various ways. The role of insulin, glucagon and growth-hormone (GH) was determined. After glucose loading the insulin response is weaker in HT than in euthyroid subjects. Enhanced degradation of insulin has been reported. It is suggested that in HT the serum insulin concentration declines at a slightly accelerated rate. In HT the deranged carbohydrate metabolism might be a consequence of altered tissue sensitivity to insulin. To elucidate this problem insulin receptors on erythrocytes obtained from hyperthyroid women were investigated. The maximal specific binding of /sup 125/I-insulin to RBC of hyperthyroid patients was decreased and the analysis refers to a decreased receptor concentration in RBC. The nature of glucagon secretion and its influence on glucose metabolism in HT was investigated. The basal plasma glucagon is elevated in hyperthyroid patients. The suppression of glucagon secretion induced by an oral glucose loading was of significantly lesser degree in hyperthyroid patients than in controls. Applying the erythrocyte receptor assay a decreased specific binding of /sup 125/I-glucagon to RBC of hyperthyroid patients has been found and data indicate a significantly less glucagon receptor concentration in thyrotoxicosis. Physiological elevations of serum GH levels led to a significant impairment of glucose metabolism. Beside the GH-RH and somatostatin, the dopaminergic neurotransmitter system participates in the regulation of GH secretion too. It has been demonstrated that after administration of the dopamine agonist l-dopa the GH response was weaker in HT than in controls. This indicates that in thyrotoxicosis the GH secretion can not be stimulated in such a degree as in euthyroidism.

Radiation impairs perineural invasion by modulating the nerve microenvironment.

Directory of Open Access Journals (Sweden)

Richard L Bakst

Full Text Available Perineural invasion (PNI by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control PNI remain undefined.An in vitro co-culture system of dorsal root ganglia (DRG and pancreatic cancer cells was used as a model of PNI. An in vivo murine sciatic nerve model was used to study how RT to nerve or cancer affects nerve invasion by cancer.Cancer cell invasion of the DRG was partially dependent on DRG secretion of glial-derived neurotrophic factor (GDNF. A single 4 Gy dose of radiation to the DRG alone, cultured with non-radiated cancer cells, significantly inhibited PNI and was associated with decreased GDNF secretion but intact DRG viability. Radiation of cancer cells alone, co-cultured with non-radiated nerves, inhibited PNI through predominantly compromised cancer cell viability. In a murine model of PNI, a single 8 Gy dose of radiation to the sciatic nerve prior to implantation of non-radiated cancer cells resulted in decreased GDNF expression, decreased PNI by imaging and histology, and preservation of sciatic nerve motor function.Radiation may impair PNI through not only direct effects on cancer cell viability, but also an independent interruption of paracrine mechanisms underlying PNI. RT modulation of the nerve microenvironment may decrease PNI, and hold significant therapeutic implications for RT dosing and field design for patients with cancers exhibiting PNI.

Inhibition of Non Canonical HIV-1 Tat Secretion Through the Cellular Na+,K+-ATPase Blocks HIV-1 Infection

Directory of Open Access Journals (Sweden)

Silvia Agostini

2017-07-01

Full Text Available Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na+,K+-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity. Treatment of CD4+ T-cells with short peptides corresponding to the Tat-binding regions of the pump alpha subunit impaired extracellular Tat release and blocked HIV-1 replication. Thus, non canonical, extracellular Tat secretion is essential for viral infectivity.

Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review.

Science.gov (United States)

Maresch, Constanze C; Stute, Dina C; Alves, Marco G; Oliveira, Pedro F; de Kretser, David M; Linn, Thomas

2018-01-01

Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing. Impaired regulation of glucose and the resultant hyperglycemia are major threats to the health of individuals in modern societies especially given the rapidly rising prevalence affecting an increasing number of men in their reproductive years. Consequently, diabetes-induced hyperglycemia is likely to contribute to a decline in global birth rates especially in those societies with a high diabetic prevalence. This systematic review addresses and summarizes the impact of hyperglycemia on male reproductive health with a particular emphasis on the molecular mechanisms that influence the testis and other parts of the male reproductive tract. A systematic search of the literature published in the MEDLINE-Pubmed database (http://www.ncbi.nlm.nih.gov/pubmed) and Cochrane Library (http://www.cochranelibrary.com) was performed, as well as hand searching reference lists, from the earliest available online indexing year until May 2017, using diabetes- and male fertility-related keywords in combination with other search phrases relevant to the topic of hyperglycemia. Inclusion criteria were: clinical studies on type 1 diabetic (T1D) men and studies on T1D animal models with a focus on reproductive parameters. Case reports/series, observational studies and clinical trials were included. Studies on patients with type 2 diabetes (T2D) or animal models of T2D were excluded to distinguish hyperglycemia from other metabolic effects. A total

Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

Science.gov (United States)

Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

2012-01-01

The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

Cyclosporin A impairs the secretion and activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat).

Science.gov (United States)

Hershko, Klilah; Simhadri, Vijaya L; Blaisdell, Adam; Hunt, Ryan C; Newell, Jordan; Tseng, Sandra C; Hershko, Alon Y; Choi, Jae Won; Sauna, Zuben E; Wu, Andrew; Bram, Richard J; Komar, Anton A; Kimchi-Sarfaty, Chava

2012-12-28

The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients.

Honeybee Foraging, Nectar Secretion, and Honey Potential of Wild Jujube Trees, Ziziphus nummularia.

Science.gov (United States)

Alqarni, A S

2015-06-01

Ziziphus trees are of economic importance due to their aggregated value (source of fruits and timber) and are the most important melliferous plants in the Arabian Peninsula. Interaction between honeybees and Ziziphus nummularia was investigated by assessing foraging, flower phenology, nectar secretion, and honey potential. It is demonstrate that both the native Apis mellifera jemenitica Ruttner and the exotic Apis mellifera carnica Pollmann foraged on Z. nummularia flowers. Bee foraging for nectar and pollen was low (2 ± 0.7 workers/200 flowers/3 min) during early morning and increased to a peak in the afternoon (100 ± 15 workers/200 flowers/3 min). Remarkable foraging activity was recorded during high temperature (35°C) and low humidity (20%) conditions. Foraging for nectar collection was more distinct than that for pollen. The flowering of Z. nummularia was gradual, and was characterized by some flowers that opened and secreted nectar early before sunrise, whereas other flowers remained opened until sunrise. The flowers lasted 2 days, with 83% of nectar secreted in the first day. The peak of nectar secretion was recorded at noon under hot and dry conditions. The lowest amount of nectar was secreted during sunrise under mild temperature (24°C) and humidity (31%) conditions. Under optimum conditions, it is assumed that the average sugar mass was 0.321 ± 0.03 mg TSS/flower, while the total sugar mass was 27.65 ± 11 g/tree. The average honey production potential of tested Z. nummularia was approximately 2.998 kg/tree and 749.475 kg/ha in the main flowering season.

Physiological and Molecular Analysis of Aluminium-Induced Organic Acid Anion Secretion from Grain Amaranth (Amaranthus hypochondriacus L.) Roots

OpenAIRE

Fan, Wei; Xu, Jia-Meng; Lou, He-Qiang; Xiao, Chuan; Chen, Wei-Wei; Yang, Jian-Li

2016-01-01

Grain amaranth (Amaranthus hypochondriacus L.) is abundant in oxalate and can secrete oxalate under aluminium (Al) stress. However, the features of Al-induced secretion of organic acid anions (OA) and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH) together with quantitative real-time PCR (qRT-PCR) was used t...

RSA-Based Secret Handshakes

OpenAIRE

Vergnaud , Damien

2006-01-01

A secret handshake mechanism allows two entities, members of a same group, to authenticate each other secretly. This primitive was introduced recently by Balfanz, Durfee, Shankar, Smetters, Staddon and Wong and, so far, all the schemes proposed are based on discrete log systems. This paper proposes three new secret handshake protocols secure against active impersonator and detector adversaries. Inspired by two RSA-based key agreement protocols introduced by Okamoto and Tanaka in 1989 and Gira...

Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets.

Science.gov (United States)

Qureshi, Farhan M; Dejene, Eden A; Corbin, Kathryn L; Nunemaker, Craig S

2015-05-01

In healthy pancreatic islets, glucose-stimulated changes in intracellular calcium ([Ca(2+)]i) provide a reasonable reflection of the patterns and relative amounts of insulin secretion. We report that [Ca(2+)]i in islets under stress, however, dissociates with insulin release in different ways for different stressors. Islets were exposed for 48h to a variety of stressors: cytokines (low-grade inflammation), 28mM glucose (28G, glucotoxicity), free fatty acids (FFAs, lipotoxicity), thapsigargin (ER stress), or rotenone (mitochondrial stress). We then measured [Ca(2+)]i and insulin release in parallel studies. Islets exposed to all stressors except rotenone displayed significantly elevated [Ca(2+)]i in low glucose, however, increased insulin secretion was only observed for 28G due to increased nifedipine-sensitive calcium-channel flux. Following 3-11mM glucose stimulation, all stressors substantially reduced the peak glucose-stimulated [Ca(2+)]i response (first phase). Thapsigargin and cytokines also substantially impacted aspects of calcium influx and ER calcium handling. Stressors did not significantly impact insulin secretion in 11mM glucose for any stressor, although FFAs showed a borderline reduction, which contributed to a significant decrease in the stimulation index (11:3mM glucose) observed for FFAs and also for 28G. We also clamped [Ca(2+)]i using 30mM KCl+250μM diazoxide to test the amplifying pathway. Only rotenone-treated islets showed a robust increase in 3-11mM glucose-stimulated insulin secretion under clamped conditions, suggesting that low-level mitochondrial stress might activate the metabolic amplifying pathway. We conclude that different stressors dissociate [Ca(2+)]i from insulin secretion differently: ER stressors (thapsigargin, cytokines) primarily affect [Ca(2+)]i but not conventional insulin secretion and 'metabolic' stressors (FFAs, 28G, rotenone) impacted insulin secretion. Copyright © 2015 Elsevier Ltd. All rights reserved.

cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

Science.gov (United States)

Dolz, Manuel; Movassat, Jamileh; Bailbé, Danielle; Le Stunff, Hervé; Giroix, Marie-Hélène; Fradet, Magali; Kergoat, Micheline; Portha, Bernard

2011-11-01

cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets. Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases. The high basal cAMP level most likely reflects an increased cAMP generation in GK/Par compared with W islets since 1) forskolin dose-dependently induced an exaggerated cAMP accumulation; 2) adenylyl cyclase (AC)2, AC3, and G(s)α proteins were overexpressed; 3) IBMX-activated cAMP accumulation was less efficient and PDE-3B and PDE-1C mRNA were decreased. Moreover, the GK/Par insulin release apparatus appears less sensitive to cAMP, since GK/Par islets released less insulin at submaximal cAMP levels and required five times more cAMP to reach a maximal secretion rate no longer different from W. GLP-1 was able to reactivate GK/Par insulin secretion so that GIIS became indistinguishable from that of W. The exaggerated cAMP production is instrumental, since GLP-1-induced GIIS reactivation was lost in the presence the AC blocker 2',5'-dideoxyadenosine. This GLP-1 effect takes place in the absence of any improvement of the [Ca(2+)](i) response and correlates with activation of the cAMP-dependent PKA-dependent pathway.

Incretin secretion in obese Korean children and adolescents with newly diagnosed type 2 diabetes.

Science.gov (United States)

Park, So Hyun; Jung, Min Ho; Cho, Won Kyoung; Park, Mi Sun; Suh, Byung Kyu

2016-01-01

The role of incretins in type 2 diabetes is controversial. This study investigated the association between incretin levels in obese Korean children and adolescents newly diagnosed with type 2 diabetes. We performed a 2-hr oral glucose tolerance test (OGTT) in obese children and adolescents with type 2 diabetes and with normal glucose tolerance. Twelve obese children and adolescents with newly diagnosed type 2 diabetes (DM group) and 12 obese age-matched subjects without type 2 diabetes (NDM group) were included. An OGTT was conducted and insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were measured during the OGTT. The mean age of the patients was 13·8 ± 2·0 years, and the mean body mass index (BMI) Z-score was 2·1 ± 0·5. The groups were comparable in age, sex, BMI Z-score and waist:hip ratio. The DM group had significantly lower homeostasis model assessment of β and insulinogenic index values (P 1). The homeostasis model assessment of insulin resistance index was not different between the two groups. Insulin and C-peptide secretions were significantly lower in the DM group than in the NDM group (P 1). Total GLP-1 secretion was significantly higher in the DM group while intact GLP-1 and GIP secretion values were not significantly different between the two groups. Impaired insulin secretion might be important in the pathogenesis of type 2 diabetes in obese Korean children and adolescents, however, which may not be attributed to incretin secretion. © 2015 John Wiley & Sons Ltd.

The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications

DEFF Research Database (Denmark)

Madsbad, S

2014-01-01

glucagon secretion from the pancreas in response to food ingestion. Evidence suggests that the action or effect of GLP-1 may be impaired in obese subjects, even in those with normal glucose tolerance. GLP-1 impairment may help explain the increased gastric emptying and decreased satiety signalling seen...... in obesity. Incretin impairment, probably associated with reduced insulinotropic potency of GLP-1, is also characteristic of type 2 diabetes (T2D). Therefore, it is possible that incretin impairment may contribute to the pathophysiological bridge between obesity and T2D. This review summarises current......The hormone glucagon-like peptide-1 (GLP-1) is released from the gut in response to food intake. It acts as a satiety signal, leading to reduced food intake, and also as a regulator of gastric emptying. Furthermore, GLP-1 functions as an incretin hormone, stimulating insulin release and inhibiting...

Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study

DEFF Research Database (Denmark)

Faerch, Kristine; Vaag, Allan; Holst, Jens J

2008-01-01

of insulin sensitivity (HOMA-IS), early-phase insulin release (EPIR), and insulin secretion relative to insulin action (disposition index) were estimated. RESULTS: Five years before the pre-diabetes diagnoses (i-IFG, i-IGT, and IFG/IGT), ISI, HOMA-IS, EPIR, and disposition index were lower than...

Efficient multiparty quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Xiao Li; Deng Fuguo; Long Guilu; Pan Jianwei

2004-01-01

In this work, we generalize the quantum-secret-sharing scheme of Hillery, Buzek, and Berthiaume [Phys. Rev. A 59, 1829 (1999)] into arbitrary multiparties. Explicit expressions for the shared secret bit is given. It is shown that in the Hillery-Buzek-Berthiaume quantum-secret-sharing scheme the secret information is shared in the parity of binary strings formed by the measured outcomes of the participants. In addition, we have increased the efficiency of the quantum-secret-sharing scheme by generalizing two techniques from quantum key distribution. The favored-measuring-basis quantum-secret-sharing scheme is developed from the Lo-Chau-Ardehali technique [H. K. Lo, H. F. Chau, and M. Ardehali, e-print quant-ph/0011056] where all the participants choose their measuring-basis asymmetrically, and the measuring-basis-encrypted quantum-secret-sharing scheme is developed from the Hwang-Koh-Han technique [W. Y. Hwang, I. G. Koh, and Y. D. Han, Phys. Lett. A 244, 489 (1998)] where all participants choose their measuring basis according to a control key. Both schemes are asymptotically 100% in efficiency, hence nearly all the Greenberger-Horne-Zeilinger states in a quantum-secret-sharing process are used to generate shared secret information

Transcriptional regulator GntR of Brucella abortus regulates cytotoxicity, induces the secretion of inflammatory cytokines and affects expression of the type IV secretion system and quorum sensing system in macrophages.

Science.gov (United States)

Li, Zhiqiang; Wang, Shuli; Zhang, Hui; Zhang, Jinliang; Xi, Li; Zhang, Junbo; Chen, Chuangfu

2017-03-01

The pathogenic mechanisms of Brucella are still poorly understood. GntR is a transcriptional regulator and plays an important role in the intracellular survival of Brucella. To investigate whether GntR is involved in the cytotoxicity of Brucella abortus (B. abortus), we created a 2308ΔgntR mutant of B. abortus 2308 (S2308). Lactate dehydrogenase (LDH) cytotoxicity assays using a murine macrophage cell line (RAW 264.7) show that high-dose infection with the parental strain produces a high level of cytotoxicity to macrophages, but the 2308ΔgntR mutant exhibits a very low level of cytotoxicity, indicating that mutation of GntR impairs the cytotoxicity of B. abortus to macrophages. After the macrophages are infected with 2308ΔgntR, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) increase and are slightly higher than that for the S2308 infected group, indicating that the 2308ΔgntR mutant could induce the secretion of inflammatory cytokines. The virulence factor detection experiments indicate that genes involved in the type IV secretion system (T4SS) and quorum sensing system (QSS) are down-regulated in 2308ΔgntR. The lower levels of survival of 2308ΔgntR under various stress conditions and the increased sensitivity of 2308ΔgntR to polymyxin B suggest that GntR is a virulence factor and that deletion of gntR reduces of B. abortus to stress conditions. Taken together, our results demonstrate that GntR is involved in the cytotoxicity, virulence and intracellular survival of B. abortus during its infection.

Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

Science.gov (United States)

Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

2010-08-01

Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work.

Science.gov (United States)

Nagashima, Shunsuke; Osawa, Madoka; Matsuyama, Hiroto; Ohoka, Wataru; Ahn, Aemi; Wakamura, Tomoko

2018-02-01

The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No

Flying under the radar: Figurative language impairments in focal lesion patients

Directory of Open Access Journals (Sweden)

Geena Rose Ianni

2014-11-01

Full Text Available Despite the prevalent and natural use of metaphor in everyday language, the neural basis of this powerful communication device remains poorly understood. Early studies of brain-injured patients suggested the right hemisphere plays a critical role in metaphor comprehension, but more recent patient and neuroimaging studies do not consistently support this hypothesis. One explanation for this discrepancy is the challenge in designing optimal tasks for brain-injured populations. As traditional aphasia assessments do not assess figurative language comprehension, we designed a new metaphor comprehension task to consider whether impaired metaphor processing is missed by standard clinical assessments. Stimuli consisted of 60 pairs of moderately familiar metaphors and closely matched literal sentences. Sentences were presented visually in a randomized order, followed by four adjective-noun answer choices (target + three foil types. Participants were instructed to select the phrase that best matched the meaning of the sentence. We report the performance of three focal lesion patients and a group of 12 healthy, older controls. Controls performed near ceiling in both conditions, with slightly more accurate performance on literal than metaphoric sentences. While the Western Aphasia Battery (Kertesz, 1982 and the Objects and Actions Naming Battery (Druks, 1992 indicated minimal to no language difficulty, our metaphor comprehension task indicated three different profiles of metaphor comprehension impairment in the patients’ performance. Single case statistics revealed comparable impairment on metaphoric and literal sentences, disproportionately greater impairment on metaphors than literal sentences, and selective impairment on metaphors. We conclude our task reveals that patients can have selective metaphor comprehension deficits. These deficits are not captured by traditional neuropsychological language assessments, suggesting overlooked communication

Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis - limitations for the underlying COPD detection.

Science.gov (United States)

Radovic, Milan; Ristic, Lidija; Ciric, Zorica; Dinic-Radovic, Violeta; Stankovic, Ivana; Pejcic, Tatjana; Rancic, Milan; Bogdanovic, Dragan

2016-01-01

During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. Prospective, nest case-control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (Ppulmonary tuberculosis lesions (OR 1.01-1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02-1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel dust exposure. Initial spirometry testing in patients with active PTB is not a sufficient and accurate approach in the detection of underlying COPD, which may lead to their further potential health deterioration.

Enteroendocrine secretion of gut hormones in diabetes, obesity and after bariatric surgery

DEFF Research Database (Denmark)

Holst, Jens Juul

2013-01-01

Gastric bypass surgery is associated with a major weight loss and often causes remission in patients with type 2 diabetes. Surgery is also associated with dramatic increases in the secretion of the gut hormones, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), both of which regulate appetite...... and food intake, while GLP-1 in addition functions as an incretin hormone, stimulating insulin secretion. It has been possible to probe the role of GLP-1 for the diabetes resolution after gastric bypass using a GLP-1 receptor antagonist, and it is clear that the enhanced beta cell sensitivity to glucose...... which underlies the enhanced insulin secretion in the patients after the operation depends critically on the increased GLP-1 secretion. Both hormones seem to contribute importantly to the reduction in food intake after bypass and, therefore, to the weight loss. Currently, there are no data to indicate...

Quantum secret sharing using orthogonal multiqudit entangled states

Science.gov (United States)

Bai, Chen-Ming; Li, Zhi-Hui; Liu, Cheng-Ji; Li, Yong-Ming

2017-12-01

In this work, we investigate the distinguishability of orthogonal multiqudit entangled states under restricted local operations and classical communication. According to these properties, we propose a quantum secret sharing scheme to realize three types of access structures, i.e., the ( n, n)-threshold, the restricted (3, n)-threshold and restricted (4, n)-threshold schemes (called LOCC-QSS scheme). All cooperating players in the restricted threshold schemes are from two disjoint groups. In the proposed protocol, the participants use the computational basis measurement and classical communication to distinguish between those orthogonal states and reconstruct the original secret. Furthermore, we also analyze the security of our scheme in four primary quantum attacks and give a simple encoding method in order to better prevent the participant conspiracy attack.

A two-dimensional electrophoretic profile of the proteins secreted by Herbaspirillum seropedicae strain Z78.

Science.gov (United States)

Chaves, Daniela Fojo Seixas; de Souza, Emanuel Maltempi; Monteiro, Rose Adele; de Oliveira Pedrosa, Fábio

2009-11-02

Herbaspirillum seropedicae is an endophytic bacterium that associates with rice, sugarcane and other economically important crops. Secreted proteins play a key role in the plant-bacterial interaction. Using 2D electrophoresis and peptide mass fingerprint mass spectrometry, 63 protein spots representing 41 different secreted proteins were identified during growth of H. seropedicae under nitrogen-sufficient conditions. In silico analysis showed that 25.4% of the proteins had signal peptides and 15.9% were predicted to be non-classically secreted. Among the most abundant were flagellar components and ABC-type transport system proteins. Nine secreted proteins had also been identified in the cellular proteome, suggesting that they also play a role in the extracellular environment. No type III secreted proteins were detected by comparison of the wild type strain with an hrcN mutant strain.

Epstein Barr virus Latent Membrane Protein-1 enhances dendritic cell therapy lymph node migration, activation, and IL-12 secretion.

Directory of Open Access Journals (Sweden)

James M Termini

Full Text Available Dendritic cells (DC are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1 of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5 expressing LMP1 under the control of a Tet-inducible promoter. Ad5-LMP1 was found to mature and activate both human and mouse DC. LMP1 enhanced in vitro migration of DC toward CCL19, as well as in vivo migration of DC to the inguinal lymph nodes of mice following intradermal injection. LMP1-transduced DC increased T cell proliferation in a Pmel-1 adoptive transfer model and enhanced survival in B16-F10 melanoma models. LMP1-DC also enhanced protection in a vaccinia-Gag viral challenge assay. LMP1 induced high levels of IL-12p70 secretion in mouse DC when compared to standard maturation protocols. Importantly, LMP1-transduced human DC retained the capacity to secrete IL-12p70 and TNF in response to DC restimulation. In contrast, DC matured with Monocyte Conditioned Media-Mimic cocktail (Mimic were impaired in IL-12p70 secretion following restimulation. Overall, LMP1 matured and activated DC, induced migration to the lymph node, and generated high levels of IL-12p70 in a murine model. We propose LMP1 as a promising molecular adjuvant for DC vaccines.

The voltage-gated proton channel Hv1 is expressed in pancreatic islet β-cells and regulates insulin secretion

Energy Technology Data Exchange (ETDEWEB)

Zhao, Qing [Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071 (China); Che, Yongzhe [School of Medicine, Nankai University, Tianjin 300071 (China); Li, Qiang; Zhang, Shangrong [Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071 (China); Gao, Ying-Tang [Key Laboratory of Artificial Cell, Third Central Clinical College of Tianjin Medical University, Tianjin 300170 (China); Wang, Yifan; Wang, Xudong; Xi, Wang; Zuo, Weiyan [Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071 (China); Li, Shu Jie, E-mail: shujieli@nankai.edu.cn [Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071 (China)

2015-12-25

The voltage-gated proton channel Hv1 is a potent acid extruder that participates in the extrusion of the intracellular acid. Here, we showed for the first time, Hv1 is highly expressed in mouse and human pancreatic islet β-cells, as well as β-cell lines. Imaging studies demonstrated that Hv1 resides in insulin-containing granules in β-cells. Knockdown of Hv1 with RNA interference significantly reduces glucose- and K{sup +}-induced insulin secretion in isolated islets and INS-1 (832/13) β-cells and has an impairment on glucose- and K{sup +}-induced intracellular Ca{sup 2+} homeostasis. Our data demonstrated that the expression of Hv1 in pancreatic islet β-cells regulates insulin secretion through regulating Ca{sup 2+} homeostasis.

Prelysosomal Compartments in the Unconventional Secretion of Amyloidogenic Seeds

Directory of Open Access Journals (Sweden)

Helena Borland

2017-01-01

Full Text Available A mechanistic link between neuron-to-neuron transmission of secreted amyloid and propagation of protein malconformation cytopathology and disease has recently been uncovered in animal models. An enormous interest in the unconventional secretion of amyloids from neurons has followed. Amphisomes and late endosomes are the penultimate maturation products of the autophagosomal and endosomal pathways, respectively, and normally fuse with lysosomes for degradation. However, under conditions of perturbed membrane trafficking and/or lysosomal deficiency, prelysosomal compartments may instead fuse with the plasma membrane to release any contained amyloid. After a brief introduction to the endosomal and autophagosomal pathways, we discuss the evidence for autophagosomal secretion (exophagy of amyloids, with a comparative emphasis on Aβ1–42 and α-synuclein, as luminal and cytosolic amyloids, respectively. The ESCRT-mediated import of cytosolic amyloid into late endosomal exosomes, a known vehicle of transmission of macromolecules between cells, is also reviewed. Finally, mechanisms of lysosomal dysfunction, deficiency, and exocytosis are exemplified in the context of genetically identified risk factors, mainly for Parkinson’s disease. Exocytosis of prelysosomal or lysosomal organelles is a last resort for clearance of cytotoxic material and alleviates cytopathy. However, they also represent a vehicle for the concentration, posttranslational modification, and secretion of amyloid seeds.

[Multilingualism and specific language impairment].

Science.gov (United States)

Arkkila, Eva; Smolander, Sini; Laasonen, Marja

2013-01-01

Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

MED25 is a mediator component of HNF4α-driven transcription leading to insulin secretion in pancreatic beta-cells.

Directory of Open Access Journals (Sweden)

Eun Hee Han

Full Text Available Unique nuclear receptor Hepatocyte Nuclear Factor 4α (HNF4α is an essential transcriptional regulator for early development and proper function of pancreatic ß-cells, and its mutations are monogenic causes of a dominant inherited form of diabetes referred to as Maturity Onset Diabetes of the Young 1 (MODY1. As a gene-specific transcription factor, HNF4α exerts its function through various molecular interactions, but its protein recruiting network has not been fully characterized. Here we report the identification of MED25 as one of the HNF4α binding partners in pancreatic ß-cells leading to insulin secretion which is impaired in MODY patients. MED25 is one of the subunits of the Mediator complex that is required for induction of RNA polymerase II transcription by various transcription factors including nuclear receptors. This HNF4α-MED25 interaction was initially identified by a yeast-two-hybrid method, confirmed by in vivo and in vitro analyses, and proven to be mediated through the MED25-LXXLL motif in a ligand-independent manner. Reporter-gene based transcription assays and siRNA/shRNA-based gene silencing approaches revealed that this interaction is crucial for full activation of HNF4α-mediated transcription, especially expression of target genes implicated in glucose-stimulated insulin secretion. Selected MODY mutations at the LXXLL motif binding pocket disrupt these interactions and cause impaired insulin secretion through a 'loss-of-function' mechanism.

The Best kept Secrets In Government.

Science.gov (United States)

1996-09-01

external events that could disrupt energy supplies and services. • Science and Technology. We use the unique resources of the Department’s laboratories...1996. There is no doubt that access to and 96 Appendix A use of the Internet will be a big factor enabling GSA employees to compete in the coming...workers. 113 The Best Kept Secrets In Government • Sweatshops are under attack. More than 50 manufacturing firms across the country have com

Proteomic analysis of rutin-induced secreted proteins from Aspergillus flavus.

Science.gov (United States)

Medina, Martha L; Kiernan, Urban A; Francisco, Wilson A

2004-03-01

Few studies have been conducted to identify the extracellular proteins and enzymes secreted by filamentous fungi, particularly with respect to dispensable metabolic pathways. Proteomic analysis has proven to be the most powerful method for identification of proteins in complex mixtures and is suitable for the study of the alteration of protein expression under different environmental conditions. The filamentous fungus Aspergillus flavus can degrade the flavonoid rutin as the only source of carbon via an extracellular enzyme system. In this study, a proteomic analysis was used to differentiate and identify the extracellular rutin-induced and non-induced proteins secreted by A. flavus. The secreted proteins were analyzed by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. While 15 rutin-induced proteins and 7 non-induced proteins were identified, more than 90 protein spots remain unidentified, indicating that these proteins are either novel proteins or proteins that have not yet been sequenced.

A trade secret model for genomic biobanking.

Science.gov (United States)

Conley, John M; Mitchell, Robert; Cadigan, R Jean; Davis, Arlene M; Dobson, Allison W; Gladden, Ryan Q

2012-01-01

Genomic biobanks present ethical challenges that are qualitatively unique and quantitatively unprecedented. Many critics have questioned whether the current system of informed consent can be meaningfully applied to genomic biobanking. Proposals for reform have come from many directions, but have tended to involve incremental change in current informed consent practice. This paper reports on our efforts to seek new ideas and approaches from those whom informed consent is designed to protect: research subjects. Our model emerged from semi-structured interviews with healthy volunteers who had been recruited to join either of two biobanks (some joined, some did not), and whom we encouraged to explain their concerns and how they understood the relationship between specimen contributors and biobanks. These subjects spoke about their DNA and the information it contains in ways that were strikingly evocative of the legal concept of the trade secret. They then described the terms and conditions under which they might let others study their DNA, and there was a compelling analogy to the commonplace practice of trade secret licensing. We propose a novel biobanking model based on this trade secret concept, and argue that it would be a practical, legal, and ethical improvement on the status quo. © 2012 American Society of Law, Medicine & Ethics, Inc.

Incretin secretion: direct mechanisms

DEFF Research Database (Denmark)

Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

2014-01-01

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

Proximal Tubular Secretion of Creatinine by Organic Cation Transporter OCT2 in Cancer Patients

Science.gov (United States)

Ciarimboli, Giuliano; Lancaster, Cynthia S.; Schlatter, Eberhard; Franke, Ryan M.; Sprowl, Jason A.; Pavenstädt, Hermann; Massmann, Vivian; Guckel, Denise; Mathijssen, Ron H. J.; Yang, Wenjian; Pui, Ching-Hon; Relling, Mary V.; Herrmann, Edwin; Sparreboom, Alex

2012-01-01

Purpose Knowledge of transporters responsible for the renal secretion of creatinine is key to a proper interpretation of serum creatinine and/or creatinine clearance as markers of renal function in cancer patients receiving chemotherapeutic agents. Experimental Design Creatinine transport was studied in transfected HEK293 cells in vitro and in wildtype mice and age-matched organic cation transporter 1 and 2-deficient [Oct1/2(−/−)] mice ex vivo and in vivo. Clinical pharmacogenetic and transport inhibition studies were done in two separate cohorts of cancer patients. Results Compared to wildtype mice, creatinine clearance was significantly impaired in Oct1/2(−/−) mice. Furthermore, creatinine inhibited organic cation transport in freshly-isolated proximal tubules from wild-type mice and humans, but not in those from Oct1/2(−/−) mice. In a genetic-association analysis (n=590), several polymorphisms around the OCT2/SLC22A2 gene locus, including rs2504954 (P=0.000873), were significantly associated with age-adjusted creatinine levels. Furthermore, in cancer patients (n=68), the OCT2 substrate cisplatin caused an acute elevation of serum creatinine (P=0.0083), consistent with inhibition of an elimination pathway. Conclusions Collectively, this study shows that OCT2 plays a decisive role in the renal secretion of creatinine. This process can be inhibited by OCT2 substrates, which impair the usefulness of creatinine as a marker of renal function. PMID:22223530

A methodology for the characterization and diagnosis of cognitive impairments-Application to specific language impairment.

Science.gov (United States)

Oliva, Jesús; Serrano, J Ignacio; del Castillo, M Dolores; Iglesias, Angel

2014-06-01

The diagnosis of mental disorders is in most cases very difficult because of the high heterogeneity and overlap between associated cognitive impairments. Furthermore, early and individualized diagnosis is crucial. In this paper, we propose a methodology to support the individualized characterization and diagnosis of cognitive impairments. The methodology can also be used as a test platform for existing theories on the causes of the impairments. We use computational cognitive modeling to gather information on the cognitive mechanisms underlying normal and impaired behavior. We then use this information to feed machine-learning algorithms to individually characterize the impairment and to differentiate between normal and impaired behavior. We apply the methodology to the particular case of specific language impairment (SLI) in Spanish-speaking children. The proposed methodology begins by defining a task in which normal and individuals with impairment present behavioral differences. Next we build a computational cognitive model of that task and individualize it: we build a cognitive model for each participant and optimize its parameter values to fit the behavior of each participant. Finally, we use the optimized parameter values to feed different machine learning algorithms. The methodology was applied to an existing database of 48 Spanish-speaking children (24 normal and 24 SLI children) using clustering techniques for the characterization, and different classifier techniques for the diagnosis. The characterization results show three well-differentiated groups that can be associated with the three main theories on SLI. Using a leave-one-subject-out testing methodology, all the classifiers except the DT produced sensitivity, specificity and area under curve values above 90%, reaching 100% in some cases. The results show that our methodology is able to find relevant information on the underlying cognitive mechanisms and to use it appropriately to provide better

Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus.

Science.gov (United States)

Cortez-Navarrete, Marisol; Martínez-Abundis, Esperanza; Pérez-Rubio, Karina G; González-Ortiz, Manuel; Villar, Miriam Méndez-Del

2018-02-12

An improvement in parameters of glycemic control has been observed with Momordica charantia in patients with type 2 diabetes mellitus (T2DM). It is unknown whether this improvement is through a modification of insulin secretion, insulin sensitivity, or both. We hypothesized that M. charantia administration can improve insulin secretion and/or insulin sensitivity in patients with T2DM, without pharmacological treatment. The objective of the study was to evaluate the effect of M. charantia administration on insulin secretion and sensitivity. A randomized, double-blinded, placebo-controlled, clinical trial was carried out in 24 patients who received M. charantia (2000 mg/day) or placebo for 3 months. A 2-h oral glucose tolerance test (OGTT) was done before and after the intervention to calculate areas under the curve (AUC) of glucose and insulin, total insulin secretion (insulinogenic index), first phase of insulin secretion (Stumvoll index), and insulin sensitivity (Matsuda index). In the M. charantia group, there were significant decreases in weight, body mass index (BMI), fat percentage, waist circumference (WC), glycated hemoglobin A1c (A1C), 2-h glucose in OGTT, and AUC of glucose. A significant increase in insulin AUC (56,562 ± 36,078 vs. 65,256 ± 42,720 pmol/L/min, P = .043), in total insulin secretion (0.29 ± 0.18 vs. 0.41 ± 0.29, P = .028), and during the first phase of insulin secretion (557.8 ± 645.6 vs. 1135.7 ± 725.0, P = .043) was observed after M. charantia administration. Insulin sensitivity was not modified with any intervention. In conclusion, M. charantia administration reduced A1C, 2-h glucose, glucose AUC, weight, BMI, fat percentage, and WC, with an increment of insulin AUC, first phase and total insulin secretion.

20 CFR 416.911 - Definition of disabling impairment.

Science.gov (United States)

2010-04-01

... with your age, education and work experience, would result in a finding that you are disabled under... combination of impairments that meets the requirements in §§ 416.920 (c) through (f). (b) If you are a child, a disabling impairment is an impairment (or combination of impairments) that causes marked and...

Cigarette company trade secrets are not secret: an analysis of reverse engineering reports in internal tobacco industry documents released as a result of litigation.

Science.gov (United States)

Velicer, Clayton; Lempert, Lauren K; Glantz, Stanton

2015-09-01

Use previously secret tobacco industry documents to assess tobacco companies' routine claims of trade secret protection for information on cigarette ingredients, additives and construction made to regulatory agencies, as well as the companies' refusal to publicly disclose this information. We analysed previously secret tobacco industry documents available at (http://legacy.library.ucsf.edu) to identify 100 examples of seven major tobacco companies' reverse engineering of their competitors' brands between 1937 and 2001. These reverse engineering reports contain detailed data for 142 different measurements for at least two companies, including physical parameters of the cigarettes, tobacco types, humectants, additives, flavourings, and smoke constituents of competitors' cigarettes. These 100 documents were distributed to 564 employees, including top managers in domestic and foreign offices across multiple departments, including executive leadership, research and design, product development, marketing and legal. These documents reported new competitors' products, measured ingredient changes over time, and informed companies' decisions regarding ingredients in their own products. Because cigarette companies routinely analyse their competitors' cigarettes in great detail, this information is neither secret nor commercially valuable and, thus, does not meet the legal definition of a 'trade secret.' This information is only being kept 'secret' from the people consuming cigarettes and the scientific community. Public agencies should release this detailed information because it would provide valuable information about how ingredients affect addictiveness and toxicity, and would help the public health community and consumers better understand the impact of cigarette design on human health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion

DEFF Research Database (Denmark)

Sasaki, S; Watanabe, J; Ohtaki, H

2017-01-01

BACKGROUND: Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate the causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is requir...

Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction.

Science.gov (United States)

Meng, Xin; Li, Jianping; Yu, Ming; Yang, Jian; Zheng, Minjuan; Zhang, Jinzhou; Sun, Chao; Liang, Hongliang; Liu, Liwen

2018-01-01

Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI. © 2017 Wiley Periodicals, Inc.

Nonlinear secret image sharing scheme.

Science.gov (United States)

Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

2014-01-01

Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively.

Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

Science.gov (United States)

Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

2013-01-01

It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

Atomic force microscopy: Unraveling the fundamental principles governing secretion and membrane fusion in cells

International Nuclear Information System (INIS)

Jena, Bhanu P.

2009-01-01

The story of cell secretion and membrane fusion is as old as life itself. Without these fundamental cellular processes known to occur in yeast to humans, life would cease to exist. In the last 15 years, primarily using the atomic force microscope, a detailed understanding of the molecular process and of the molecular machinery and mechanism of secretion and membrane fusion in cells has come to light. This has led to a paradigm shift in our understanding of the underlying mechanism of cell secretion. The journey leading to the discovery of a new cellular structure the 'porosome',-the universal secretory machinery in cells, and the contributions of the AFM in our understanding of the general molecular machinery and mechanism of cell secretion and membrane fusion, is briefly discussed in this article.

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

Science.gov (United States)

Reid, Ian A.

1994-01-01

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

β cell membrane remodelling and procoagulant events occur in inflammation-driven insulin impairment: a GLP-1 receptor dependent and independent control.

Science.gov (United States)

Gleizes, Céline; Kreutter, Guillaume; Abbas, Malak; Kassem, Mohamad; Constantinescu, Andrei Alexandru; Boisramé-Helms, Julie; Yver, Blandine; Toti, Florence; Kessler, Laurence

2016-02-01

Inflammation and hyperglycaemia are associated with a prothrombotic state. Cell-derived microparticles (MPs) are the conveyors of active procoagulant tissue factor (TF) and circulate at high concentration in diabetic patients. Liraglutide, a glucagon-like peptide (GLP)-1 analogue, is known to promote insulin secretion and β-cell preservation. In this in vitro study, we examined the link between insulin impairment, procoagulant activity and plasma membrane remodelling, under inflammatory conditions. Rin-m5f β-cell function, TF activity mediated by MPs and their modulation by 1 μM liraglutide were examined in a cell cross-talk model. Methyl-β-cyclodextrine (MCD), a cholesterol depletor, was used to evaluate the involvement of raft on TF activity, MP shedding and insulin secretion as well as Soluble N-éthylmaleimide-sensitive-factor Attachment protein Receptor (SNARE)-dependent exocytosis. Cytokines induced a two-fold increase in TF activity at MP surface that was counteracted by liraglutide. Microparticles prompted TF activity on the target cells and a two-fold decrease in insulin secretion via protein kinase A (PKA) and p38 signalling, that was also abolished by liraglutide. Large lipid raft clusters were formed in response to cytokines and liraglutide or MCD-treated cells showed similar patterns. Cells pre-treated by saturating concentration of the GLP-1r antagonist exendin (9-39), showed a partial abolishment of the liraglutide-driven insulin secretion and liraglutide-decreased TF activity. Measurement of caspase 3 cleavage and MP shedding confirmed the contribution of GLP-1r-dependent and -independent pathways. Our results confirm an integrative β-cell response to GLP-1 that targets receptor-mediated signalling and membrane remodelling pointing at the coupling of insulin secretion and inflammation-driven procoagulant events. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and

On alternative approach for verifiable secret sharing

OpenAIRE

Kulesza, Kamil; Kotulski, Zbigniew; Pieprzyk, Joseph

2002-01-01

Secret sharing allows split/distributed control over the secret (e.g. master key). Verifiable secret sharing (VSS) is the secret sharing extended by verification capacity. Usually verification comes at the price. We propose "free lunch", the approach that allows to overcome this inconvenience.

Gastrointestinal hormone secretion in women with polycystic ovary syndrome: an observational study.

Science.gov (United States)

Lin, Tzuchun; Li, Shengxian; Xu, Hua; Zhou, Huan; Feng, Rilu; Liu, Wei; Sun, Yun; Ma, Jing

2015-11-01

Is the secretion of gastrointestinal hormones impaired in patients with polycystic ovary syndrome (PCOS)? Gastrointestinal hormone levels were abnormal in patients with PCOS. The hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) are both involved in signaling satiety. Secretion of GLP-1 and PYY in response to nutrients in the small intestine plays an important role in energy metabolism. Most PCOS patients are overweight or obese, which suggests dysregulation of appetite. In order to evaluate levels of gastrointestinal hormones in PCOS, a cohort study was undertaken, involving 30 PCOS patients and 29 BMI-matched healthy women recruited from Shanghai Renji Hospital between 1 March 2013 and 30 May 2014. After an overnight fast, all participants underwent an oral glucose tolerance test. Blood was sampled frequently for measurement of blood glucose and plasma insulin, total GLP-1 and PYY concentrations. Fasting and postprandial insulin levels were significantly higher in patients with PCOS compared with the healthy controls (P controls either fasting or postprandially. PYY levels were lower in obese PCOS patients than in lean PCOS patients (P hormone responses to oral glucose rather than a physiological meal. Deficient secretion of GLP-1 and PYY does not contribute to excessive food intake in the pathophysiology of PCOS. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

Science.gov (United States)

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

Two-party secret key distribution via a modified quantum secret sharing protocol.

Science.gov (United States)

Grice, W P; Evans, P G; Lawrie, B; Legré, M; Lougovski, P; Ray, W; Williams, B P; Qi, B; Smith, A M

2015-03-23

We present and demonstrate a novel protocol for distributing secret keys between two and only two parties based on N-party single-qubit Quantum Secret Sharing (QSS). We demonstrate our new protocol with N = 3 parties using phase-encoded photons. We show that any two out of N parties can build a secret key based on partial information from each other and with collaboration from the remaining N - 2 parties. Our implementation allows for an accessible transition between N-party QSS and arbitrary two party QKD without modification of hardware. In addition, our approach significantly reduces the number of resources such as single photon detectors, lasers and dark fiber connections needed to implement QKD.

Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

Directory of Open Access Journals (Sweden)

Sylvain J Le Marchand

Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

Evidence for inhibition of steroid hormone secretion by arginine vasotocin (AVT) in tissue culture of isolated ovarian follicular cells

International Nuclear Information System (INIS)

Stoklosowa, S.; Gregoraszczuk, E.; Galas, J.; Rzasa, J.

1994-01-01

Two follicular compartments, granulosa (G) and theca interna (T) cells isolated from porcine ovaries were cultured alone or in co-culture (GT). Cells were grown as monolayers in a control medium without hormone and in a media supplemented with arginine-vasotocin (AVT) at a concentration of either 10 -7 M or 2x10 -7 M. Progesterone (P4), estrogen (E2) and androgen (A) concentrations in the culture media were taken as measures of the effect of AVT on the function of follicular cells. Steroids were analyzed by radioimmunoassay. AVT action in this culture system was expressed as a decrease in progesterone secretion by cultures of granulosa cells alone, and specially as a change in the pattern of estradiol and androgen secretion by co-cultures. Control T and G cells cultured alone secreted small amounts of A (238.0 pg/10 5 cells, respectively), and E2 272.5 pg/10 5 cells, 10.6 pg/10 5 cells, respectively) while in co-culture these two cell types interacted and the result of this positive interaction was a significant increase in secretion of these two steroids (941.0 pg/10 5 cell androgen secretion and 854.1 pg/10 5 cells estradiol secretion). This phenomenon is similar to that observed in the intact follicle 'in vivo'. AVT introduced to the culture medium impaired the effect of this positive interaction of mixed G and T cells on the production of high levels of E2 and A by untreated co-cultures. (author). 37 refs, 9 figs, 1 tab

Driving under the influence of drugs -- evaluation of analytical data of drugs in oral fluid, serum and urine, and correlation with impairment symptoms.

Science.gov (United States)

Toennes, Stefan W; Kauert, Gerold F; Steinmeyer, Stefan; Moeller, Manfred R

2005-09-10

A study was performed to acquire urine, serum and oral fluid samples in cases of suspected driving under the influence of drugs of abuse. Oral fluid was collected using a novel sampling/testing device (Dräger DrugTest System). The aim of the study was to evaluate oral fluid and urine as a predictor of blood samples positive for drugs and impairment symptoms. Analysis for cannabinoids, amphetamine and its derivatives, opiates and cocaine was performed in urine using the Mahsan Kombi/DOA4-test, in serum using immunoassay and gas chromatography-mass spectrometry (GC-MS) confirmation and in oral fluid by GC-MS. Police and medical officer observations of impairment symptoms were rated and evaluated using a threshold value for the classification of driving inability. Accuracy in correlating drug detection in oral fluid and serum were >90% for all substances and also >90% in urine and serum except for THC (71.0%). Of the cases with oral fluid positive for any drug 97.1% of corresponding serum samples were also positive for at least one drug; of drug-positive urine samples this were only 82.4%. In 119 of 146 cases, impairment symptoms above threshold were observed (81.5%). Of the cases with drugs detected in serum, 19.1% appeared not impaired which were the same with drug-positive oral fluid while more persons with drug-positive urine samples appeared uninfluenced (32.7%). The data demonstrate that oral fluid is superior to urine in correlating with serum analytical data and impairment symptoms of drivers under the influence of drugs of abuse.

Inorganic arsenic impairs differentiation and functions of human dendritic cells

International Nuclear Information System (INIS)

Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

2013-01-01

Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

Inorganic arsenic impairs differentiation and functions of human dendritic cells

Energy Technology Data Exchange (ETDEWEB)

Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

2013-01-15

Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

Inhibition of cAMP-Activated Intestinal Chloride Secretion by Diclofenac: Cellular Mechanism and Potential Application in Cholera

OpenAIRE

Pongkorpsakol, Pawin; Pathomthongtaweechai, Nutthapoom; Srimanote, Potjanee; Soodvilai, Sunhapas; Chatsudthipong, Varanuj; Muanprasat, Chatchai

2014-01-01

Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84) cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell...

Secret-key agreement over spatially correlated fast-fading multiple-antenna channels with public discussion

KAUST Repository

Zorgui, Marwen

2015-06-14

We consider secret-key agreement with public discussion over multiple-input multiple-output (MIMO) Rayleigh fast-fading channels under correlated environment. We assume that transmit, legitimate receiver and eavesdropper antennas are correlated. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge while the transmitter has only knowledge of the correlation matrices. First, we derive the expression of the secret-key capacity under the considered setup. Then, we prove that the optimal transmit strategy achieving the secret-key capacity consists in transmitting independent Gaussian signals along the eingenvectors of the transmit correlation matrix. The powers allocated to each channel mode are determined as the solution to a numerical optimization problem that we derive. A necessary and sufficient condition for beamforming (i.e., transmitting along the strongest channel mode) to be capacity-achieving is derived. Finally, we analyze the impact of correlation matrices on the system performance and provide closed-form expressions of the gain/loss due to correlation in the high power regime.

GLP-1 defects in diabetes

DEFF Research Database (Denmark)

Janus, Charlotte; Albrechtsen, Nicolai Jacob Wewer; Holst, Jens Juul

2015-01-01

with type 2 diabetes (T2D) but the underlying mechanisms are still incompletely understood. In subjects with impaired glucose tolerance (IGT) and T2D, reduced levels of circulating GLP-1 have been observed in cross-sectional studies. Regardless of other changes, a reduced GLP-1 secretion must result...... glucose disturbances to frank diabetes. Therefore, further studies are required. Ideally, longitudinal studies of predisposed subjects (i.e. obesity, first-degree relatives, post gestational diabetes) followed until diagnosis of T2D would be necessary for elucidating if, indeed, impaired GLP-1 secretion......Glucagon-like peptide-1 (GLP-1) is secreted from the intestinal L-cells upon nutrient stimulation and regulates glucose levels by stimulating secretion of insulin (insulinotropic effects) in a glucose-dependent manner (the incretin effect). The incretin effect is severely impaired in subjects...

Regulation of retinoschisin secretion in Weri-Rb1 cells by the F-actin and microtubule cytoskeleton.

Directory of Open Access Journals (Sweden)

Eiko Kitamura

Full Text Available Retinoschisin is encoded by the gene responsible for X-linked retinoschisis (XLRS, an early onset macular degeneration that results in a splitting of the inner layers of the retina and severe loss in vision. Retinoschisin is predominantly expressed and secreted from photoreceptor cells as a homo-oligomer protein; it then associates with the surface of retinal cells and maintains the retina cellular architecture. Many missense mutations in the XLRS1 gene are known to cause intracellular retention of retinoschisin, indicating that the secretion process of the protein is a critical step for its normal function in the retina. However, the molecular mechanisms underlying retinoschisin's secretion remain to be fully elucidated. In this study, we investigated the role of the F-actin cytoskeleton in the secretion of retinoschisin by treating Weri-Rb1 cells, which are known to secrete retinoschisin, with cytochalasin D, jasplakinolide, Y-27632, and dibutyryl cGMP. Our results show that cytochalasin D and jasplakinolide inhibit retinoschisin secretion, whereas Y-27632 and dibutyryl cGMP enhance secretion causing F-actin alterations. We also demonstrate that high concentrations of taxol, which hyperpolymerizes microtubules, inhibit retinoschisin secretion. Our data suggest that retinoschisin secretion is regulated by the F-actin cytoskeleton, that cGMP or inhibition of ROCK alters F-actin structure enhancing the secretion, and that the microtubule cytoskeleton is also involved in this process.

Regulation of Retinoschisin Secretion in Weri-Rb1 Cells by the F-Actin and Microtubule Cytoskeleton

Science.gov (United States)

Kitamura, Eiko; Gribanova, Yekaterina E.; Farber, Debora B.

2011-01-01

Retinoschisin is encoded by the gene responsible for X-linked retinoschisis (XLRS), an early onset macular degeneration that results in a splitting of the inner layers of the retina and severe loss in vision. Retinoschisin is predominantly expressed and secreted from photoreceptor cells as a homo-oligomer protein; it then associates with the surface of retinal cells and maintains the retina cellular architecture. Many missense mutations in the XLRS1 gene are known to cause intracellular retention of retinoschisin, indicating that the secretion process of the protein is a critical step for its normal function in the retina. However, the molecular mechanisms underlying retinoschisin's secretion remain to be fully elucidated. In this study, we investigated the role of the F-actin cytoskeleton in the secretion of retinoschisin by treating Weri-Rb1 cells, which are known to secrete retinoschisin, with cytochalasin D, jasplakinolide, Y-27632, and dibutyryl cGMP. Our results show that cytochalasin D and jasplakinolide inhibit retinoschisin secretion, whereas Y-27632 and dibutyryl cGMP enhance secretion causing F-actin alterations. We also demonstrate that high concentrations of taxol, which hyperpolymerizes microtubules, inhibit retinoschisin secretion. Our data suggest that retinoschisin secretion is regulated by the F-actin cytoskeleton, that cGMP or inhibition of ROCK alters F-actin structure enhancing the secretion, and that the microtubule cytoskeleton is also involved in this process. PMID:21738583

5 CFR 1312.27 - Top secret control.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

Science.gov (United States)

Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

Secretion Trap Tagging of Secreted and Membrane-Spanning Proteins Using Arabidopsis Gene Traps

Science.gov (United States)

Andrew T. Groover; Joseph R. Fontana; Juana M. Arroyo; Cristina Yordan; W. Richard McCombie; Robert A. Martienssen

2003-01-01

Secreted and membrane-spanning proteins play fundamental roles in plant development but pose challenges for genetic identification and characterization. We describe a "secretion trap" screen for gene trap insertions in genes encoding proteins routed through the secretory pathway. The gene trap transposon encodes a ß-glucuronidase reporter enzyme...

Correlation of secretion of retinol and protein by the lacrimal gland

International Nuclear Information System (INIS)

Ubels, J.L.; Rismondo, V.

1986-01-01

Retinol, which is present in tears, is secreted by the lacrimal gland. Retinol secretion is stimulated by cholinergic drugs and vasoactive intestinal peptide with characteristics very similar to the exocytotic secretion of protein by the lacrimal gland, suggesting that retinol and protein are secreted by similar mechanisms. The authors investigated this by cannulating the lacrimal gland ducts of rabbits and collecting lacrimal gland fluid (LGF) under conditions of maximal flow stimulated by IV injection of pilocarpine (400 μg/kg) every 20 min for 4.5 hr. Over this period LGF protein concentration decreased 36.4% from 22.8 +/- 1.94 mg/ml to 8.29 1.86 mg/ml while retinol decreased 37% from 55.1 +/- 16.2 ng/ml to 20.4 +/- 6.5 ng/ml. The retinol/protein ratio remained constant at 2.88 ng/mg. This demonstrates a strong correlation between retinol and protein secretion, suggesting that retinol may be protein bound. To investigate binding of retinol to LGF protein, LGF was incubated with 3 H-retinol. The bound and unbound retinol were separated on a Lipidex 1000 column. Retinol binding was linear over a range of 1.25-200 nM 3 H-retinol. Binding was not inhibited by PCMBS or addition of a 100-fold excess of unlabeled retinol and was not increased by prior extraction of endogenous retinol from the LGF. This indicates that the binding of retinol to LGF protein is non-specific. Retinol therefore appears to be secreted by the lacrimal gland cells in non-specific association with protein

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

Science.gov (United States)

Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

2017-01-01

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

Directory of Open Access Journals (Sweden)

Mersedeh Tohidnezhad

2017-01-01

Full Text Available The etiology and pathogenesis of rheumatoid arthritis (RA are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP. The main objective of this work is to examine the influences of platelet-released growth factor (PRGF on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

22 CFR 1421.15 - Secret ballot.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine...

The role of the daily feeding rhythm in the regulation of the day/night rhythm in triglyceride secretion in rats.

Science.gov (United States)

Su, Yan; Foppen, Ewout; Mansur Machado, Frederico Sander; Fliers, Eric; Kalsbeek, Andries

2018-02-15

Plasma triglyceride (TG) levels show a clear daily rhythm, however, thus far it is still unknown whether this rhythm results from a daily rhythm in TG production, TG uptake or both. Previous studies have shown that feeding activity affects plasma TG concentrations, but it is not clear how the daily rhythm in feeding activity affects plasma TG concentrations. In the present study, we measured plasma TG concentrations and TG secretion rates in rats at 6 Zeitgeber times to investigate whether plasma TG concentrations and TG secretion show a daily rhythm. We found that plasma TG concentrations and TG secretion show a significant day/night rhythm. Next, we removed the daily rhythm in feeding behavior by introducing a 6-meals-a-day (6M) feeding schedule to investigate whether the daily rhythm in feeding behavior is necessary to maintain the daily rhythm in TG secretion. We found that the day/night rhythm in TG secretion was abolished under 6M feeding conditions. Hepatic apolipoprotein B (ApoB) and microsomal TG transfer protein (Mttp), which are both involved in TG secretion, also lost their daily rhythmicity under 6M feeding conditions. Together, these results indicate that: (1) the daily rhythm in TG secretion contributes to the formation of a day/night rhythm in plasma TG levels and (2) a daily feeding rhythm is essential for maintaining the daily rhythm in TG secretion.

Energy metabolism in rat mast cells in relation to histamine secretion

DEFF Research Database (Denmark)

Johansen, T

1987-01-01

1. The relation between the energy metabolism and the secretory activity of rat peritoneal mast cells has been studied by determination of the cellular content of ATP and the rate of lactate production reflecting the rate of ATP synthesis under various experimental conditions. Secretion...... and the cellular ATP content at the time of cell activation was demonstrated. This may indicate a direct link between ATP and the secretory mechanism. 3. The possibility of an increased utilization of ATP during histamine secretion was explored in mast cells exposed to metabolic inhibitors. Incubation of mast...... cells with 2-deoxyglucose (2-DG) decreased the ATP content of the cells, and a long-lasting and stable level of mast cell ATP was observed. This is explained by a small decrease in the rate of ATP-synthesis by 2-DG. In 2-DG-treated cells secretion of histamine in response to compound 48...

Anaerobic α-Amylase Production and Secretion with Fumarate as the Final Electron Acceptor in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Liu, Zihe; Österlund, Tobias; Hou, Jin

2013-01-01

In this study, we focus on production of heterologous α-amylase in the yeast Saccharomyces cerevisiae under anaerobic conditions. We compare the metabolic fluxes and transcriptional regulation under aerobic and anaerobic conditions, with the objective of identifying the final electron acceptor...... reticulum are transferred to fumarate as the final electron acceptor. This model is supported by findings that the addition of fumarate under anaerobic (but not aerobic) conditions improves cell growth, specifically in the α-amylase-producing strain, in which it is not used as a carbon source. Our results...... provide a model for the molecular mechanism of anaerobic protein secretion using fumarate as the final electron acceptor, which may allow for further engineering of yeast for improved protein secretion under anaerobic growth conditions....

Alternative protein secretion: The Mam1 ABC transporter supports secretion of M-factor linked GFP in fission yeast

International Nuclear Information System (INIS)

Kjaerulff, Soren; Mueller, Sven; Jensen, Martin Roland

2005-01-01

To examine whether the fission yeast Mam1 ABC transporter can be used for secretion of heterologous proteins, thereby bypassing the classical secretion pathway, we have analyzed chimeric forms of the M-factor precursor. It was demonstrated that GFP can be exported when fused to both the amino-terminal prosequence from mfm1 and a CaaX motif. This secretion was dependent on the Mam1 transporter and not the classical secretion pathway. The secretion efficiency of GFP, however, was relatively low and most of the reporter protein was trapped in the vacuolar membranes. Our findings suggest that the Mam1 ABC protein is a promiscuous peptide transporter that can accommodate globular proteins of a relatively large size. Furthermore, our results help in defining the sequences required for processing and secretion of natural M-factor

29 CFR 401.11 - Secret ballot.

Science.gov (United States)

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression by...

Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

Science.gov (United States)

Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

2017-07-01

Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

29 CFR 1202.4 - Secret ballot.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved, or...

The Secret of Future Victories

Science.gov (United States)

1992-02-01

Copy S of 320 copies AD--A25 0 718 IDA PAPER P-265 3 THE SECRET OF FUTURE VICTORIES Paul F. Gormnan General, USA (Retired) DTIC 05M February 1992 NAY...TYPE AND DATES COVERED IFebruary 1992 Final--June 1991-January 1992 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS The Secret of Future Victories C -MDA...8 2N0-102 IDA PAPER P-2653 THE SECRET OF FUTURE VICTORIES Paul F. Gorman General. LUSA (Retired) February 1992 Approved for public release

Current Therapies That Modify Glucagon Secretion

DEFF Research Database (Denmark)

Grøndahl, Magnus F.; Keating, Damien J.; Vilsbøll, Tina

2017-01-01

and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs. Recent Findings: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon...... may be involved in the drugs’ efficacy and safety profiles. Based on these findings, modulation of glucagon secretion seems to play a hitherto underestimated role in the efficacy and safety of several glucose-lowering drugs. Summary: Numerous drugs currently available to diabetologists are capable...... of altering glucagon secretion: metformin, sulfonylurea compounds, insulin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors and amylin mimetics. Their diverse effects on glucagon secretion are of importance for their individual efficacy...

Characterization of a secreted Chlamydia protease

DEFF Research Database (Denmark)

Shaw, A.C.; Vandahl, B.B.; Larsen, M.R.

2002-01-01

Chlamydiae are obligate intracellular bacteria that are important human pathogens. The Chlamydia genomes contain orthologues to secretion apparatus proteins from other intracellular bacteria, but only a few secreted proteins have been identified. Most likely, effector proteins are secreted in order...... to promote infection. Effector proteins cannot be identified by motif or similarity searches. As a new strategy for identification of secreted proteins we have compared 2D-PAGE profiles of [35S]-labelled Chlamydia proteins from whole lysates of infected cells to 2D-PAGE profiles of proteins from purified...... Chlamydia. Several secretion candidates from Chlamydia trachomatis D and Chlamydia pneumoniae were detected by this method. Two protein spots were identified among the candidates. These represent fragments of the 'chlamydial protease- or proteasome-like activity factor' (CPAF) and were clearly present in 2D...

5 CFR 2421.15 - Secret ballot.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of a...

29 CFR 452.97 - Secret ballot.

Science.gov (United States)

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in appropriate...

Effect of single physical exercise at 35% VO2 max. intensity on secretion activity of pancreas β-cells and 125J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus

International Nuclear Information System (INIS)

Szczesniak, L.; Rychlewski, T.; Banaszak, F.; Kasprzak, Z.; Walczak, M.

1994-01-01

In this report we showed research results of effect of single physical exercise on cycloergometer at 35% VO 2 max. intensity on 125 J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus, secreting and non-secreting endogenous insulin. Insulin secretion was evaluated by measurement of C-peptide by Biodet test (Serono) of sensitivity threshold at 0.3 μg/ml. We indicated in children non-secreting endogenous insulin (n=32) there is statistically essential lower 125 J-insulin binding with erythrocyte receptor in comparison to children group with C-peptide. Physical exercise on cycloergometer at 35% VO 2 max. intensity caused different reaction in range of physiological indices, like acid-base parameters, level of glucose and 125 J-insulin binding and degradation. In children devoid of endogenous insulin we indicated statistically nonessential changes in 125 J-insulin degradation by non-impaired erythrocytes and by hemolizate, as well. 125 J-insulin binding after physical exercise increased in both groups, though change amplitude was different. Obtained research results allowed us to conclude, in children with I-type diabetes, that in dependence of impairment degree of pancreas βcells sensitivity of insulin receptor and/or number of receptors on erythrocyte surface is different

Secretive eating among youth with overweight or obesity.

Science.gov (United States)

Kass, Andrea E; Wilfley, Denise E; Eddy, Kamryn T; Boutelle, Kerri N; Zucker, Nancy; Peterson, Carol B; Le Grange, Daniel; Celio-Doyle, Angela; Goldschmidt, Andrea B

2017-07-01

Secretive eating, characterized by eating privately to conceal being seen, may reflect eating- and/or body-related shame, be associated with depression, and correlate with binge eating, which predicts weight gain and eating disorder onset. Increasing understanding of secretive eating in youth may improve weight status and reduce eating disorder risk. This study evaluated the prevalence and correlates of secretive eating in youth with overweight or obesity. Youth (N = 577) presented to five research/clinical institutions. Using a cross-sectional design, secretive eating was evaluated in relation to eating-related and general psychopathology via linear and logistic regression analyses. Secretive eating was endorsed by 111 youth, who were, on average, older than youth who denied secretive eating (mean age = 12.07 ± 2.83 versus 10.97 ± 2.31). Controlling for study site and age, youth who endorsed secretive eating had higher eating-related psychopathology and were more likely to endorse loss of control eating and purging than their counterparts who did not endorse secretive eating. Groups did not differ in excessive exercise or behavioral problems. Dietary restraint and purging were elevated among adolescents (≥13y) but not children (<13y) who endorsed secretive eating; depression was elevated among children, but not adolescents, who endorsed secretive eating. Secretive eating may portend heightened risk for eating disorders, and correlates of secretive eating may differ across pediatric development. Screening for secretive eating may inform identification of problematic eating behaviors, and understanding factors motivating secretive eating may improve intervention tailoring. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulmonary surfactant and its components inhibit secretion of phosphatidylcholine from cultured rat alveolar type II cells

International Nuclear Information System (INIS)

Dobbs, L.G.; Wright, J.R.; Hawgood, S.; Gonzalez, R.; Venstrom, K.; Nellenbogen, J.

1987-01-01

Pulmonary surfactant is synthesized and secreted by alveolar type II cells. Radioactive phosphatidylcholine has been used as a marker for surfactant secretion. The authors report findings that suggest that surfactant inhibits secretion of 3 H-labeled phosphatidylcholine by cultured rat type II cells. The lipid components and the surfactant protein group of M/sub r/ 26,000-36,000 (SP 26-36) inhibit secretion to different extents. Surfactant lipids do not completely inhibit release; in concentrations of 100 μg/ml, lipids inhibit stimulated secretion by 40%. SP 26-36 inhibits release with an EC 50 of 0.1 μg/ml. At concentrations of 1.0 μg/ml, SP 26-36 inhibits basal secretion and reduces to basal levels secretion stimulated by terbutaline, phorbol 12-myristate 13-acetate, and the ionophore A23187. The inhibitory effect of SP 26-36 can be blocked by washing type II cells after adding SP 26-36, by heating the proteins to 100 0 C for 10 min, by adding antiserum specific to SP 26-36, or by incubating cells in the presence of 0.2 mM EGTA. SP 26-36 isolated from canine and human sources also inhibits phosphatidylcholine release from rat type II cells. Neither type I collagen nor serum apolipoprotein A-1 inhibits secretion. These findings are compatible with the hypothesis that surfactant secretion is under feedback regulatory control

Extracellular secretion of a recombinant therapeutic peptide by Bacillus halodurans utilizing a modified flagellin type III secretion system

CSIR Research Space (South Africa)

Berger, E

2011-08-01

Full Text Available further 3.5-fold increase in the secretion of recombinant peptide fusions. Conclusions: The type III flagellar secretion system of B. halodurans has been shown to successfully secrete a therapeutic peptide as a heterologous flagellin fusion. Improvements...

Pituitary-hormone secretion by thyrotropinomas

NARCIS (Netherlands)

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading

Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis

Directory of Open Access Journals (Sweden)

Anita Balázs

2018-05-01

Full Text Available Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP, therefore we aimed to (i investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii to correlate the mucus phenotype with epithelial ion transport function.Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production.Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression.Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

Impaired incretin effect is an early sign of glucose dysmetabolism in nondiabetic patients with psoriasis

DEFF Research Database (Denmark)

Gyldenløve, M; Lauritsen, Tina Vilsbøll; Zachariae, Claus

2015-01-01

BACKGROUND: Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed...... the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined. OBJECTIVE: To investigate whether the incretin effect, gastrointestinal-mediated glucose disposal (GIGD) and/or secretion of glucagon...... and gut incretin hormones are impaired in normal glucose-tolerant patients with psoriasis. METHODS: Oral glucose tolerance tests and intravenous isoglycaemic glucose infusions were performed in 12 patients with moderate-to-severe psoriasis and 12 healthy matched control subjects. RESULTS: In patients...

Evidence for inhibition of steroid hormone secretion by arginine vasotocin (AVT) in tissue culture of isolated ovarian follicular cells

Energy Technology Data Exchange (ETDEWEB)

Stoklosowa, S.; Gregoraszczuk, E.; Galas, J. [Uniwersytet Jagiellonski, Cracow (Poland); Rzasa, J. [Akademia Rolnicza, Cracow (Poland)

1994-12-31

Two follicular compartments, granulosa (G) and theca interna (T) cells isolated from porcine ovaries were cultured alone or in co-culture (GT). Cells were grown as monolayers in a control medium without hormone and in a media supplemented with arginine-vasotocin (AVT) at a concentration of either 10{sup -7} M or 2x10{sup -7} M. Progesterone (P4), estrogen (E2) and androgen (A) concentrations in the culture media were taken as measures of the effect of AVT on the function of follicular cells. Steroids were analyzed by radioimmunoassay. AVT action in this culture system was expressed as a decrease in progesterone secretion by cultures of granulosa cells alone, and specially as a change in the pattern of estradiol and androgen secretion by co-cultures. Control T and G cells cultured alone secreted small amounts of A (238.0 pg/10{sup 5} cells, respectively), and E2 (272.5 pg/10{sup 5} cells, 10.6 pg/10{sup 5} cells, respectively) while in co-culture these two cell types interacted and the result of this positive interaction was a significant increase in secretion of these two steroids (941.0 pg/10{sup 5} cell androgen secretion and 854.1 pg/10{sup 5} cells estradiol secretion). This phenomenon is similar to that observed in the intact follicle `in vivo`. AVT introduced to the culture medium impaired the effect of this positive interaction of mixed G and T cells on the production of high levels of E2 and A by untreated co-cultures. (author). 37 refs, 9 figs, 1 tab.

Normal and abnormal secretion by haemopoietic cells

Science.gov (United States)

STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

2001-01-01

The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

Field-relevant doses of the systemic insecticide fipronil and fungicide pyraclostrobin impair mandibular and hypopharyngeal glands in nurse honeybees (Apis mellifera).

Science.gov (United States)

Zaluski, Rodrigo; Justulin, Luis Antonio; Orsi, Ricardo de Oliveira

2017-11-09

Global decreases in bee populations emphasize the importance of assessing how environmental stressors affect colony maintenance, especially considering the extreme task specialization observed in honeybee societies. Royal jelly, a protein secretion essential to colony nutrition, is produced by nurse honeybees, and development of bee mandibular glands, which comprise a reservoir surrounded by secretory cells and hypopharyngeal glands that are shaped by acini, is directly associated with production of this secretion. Here, we examined individual and combined effects of the systemic fungicide pyraclostrobin and insecticide fipronil in field-relevant doses (850 and 2.5 ppb, respectively) on mandibular and hypopharyngeal glands in nurse honeybees. Six days of pesticide treatment decreased secretory cell height in mandibular glands. When pyraclostrobin and fipronil were combined, the reservoir volume in mandibular glands also decreased. The total number of acini in hypopharyngeal glands was not affected, but pesticide treatment reduced the number of larger acini while increasing smaller acini. These morphological impairments appeared to reduce royal jelly secretion by nurse honeybees and consequently hampered colony maintenance. Overall, pesticide exposure in doses close to those experienced by bees in the field impaired brood-food glands in nurse honeybees, a change that could negatively influence development, survival, and colony maintenance.

Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective analysis.

Science.gov (United States)

Guarnotta, Valentina; Ciresi, Alessandro; Pillitteri, Giuseppe; Giordano, Carla

2018-05-01

Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement of anthropometric and metabolic parameters. The aim of the study was to evaluate the effects of DR-HC on insulin secretion and sensitivity and cardiometabolic risk, indirectly expressed by the visceral adiposity index (VAI). Retrospective analysis of 49 patients, 13 with primary and 36 with secondary adrenal insufficiency (AI), respectively, on conventional glucocorticoid treatment at baseline and switched to DR-HC for 36 months. Overall, 24 patients had AI-pre-diabetes (impaired fasting glucose, impaired glucose tolerance and the combination), and 25 had AI-normal glucose tolerance (NGT). Clinical and metabolic parameters, including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia, AUC 2 h insulinaemia , oral disposition index [Dio] and ISI-Matsuda), were evaluated. In patients with AI-NGT and AI-prediabetes, a significant decrease in BMI (P = .017 and P 36 and P = .043) was, respectively, observed. In addition, in prediabetic patients, only we found a significant decrease in insulinaemia (P = .014), AUC 2 h insulinaemia (P = .038) and VAI (P = .001), in concomitance with a significant increase in DIo (P = .041) and ISI-Matsuda (P = .038). Long-term DR-HC therapy is associated with an improvement in insulin secretion and sensitivity in patients with prediabetes. However, all patients appear to benefit from the treatment in terms of improvement of metabolic and anthropometric parameters. Larger studies are required to confirm our preliminary data. © 2018 John Wiley & Sons Ltd.

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

Energy Technology Data Exchange (ETDEWEB)

Srivastava, Ritesh K.; Li, Changzhao [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Wang, Yong [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Weng, Zhiping; Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Harrod, Kevin S. [Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S., E-mail: treena@uab.edu [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

2016-10-01

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

International Nuclear Information System (INIS)

Srivastava, Ritesh K.; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A.; Harrod, Kevin S.; Deshane, Jessy S.; Athar, Mohammad

2016-01-01

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4 +/+ wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4 +/− heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca ++ homeostasis. ATO induces Ca ++ -dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca ++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4 +/− mice. • Changes in macrophage

Some Economics of Trade Secret Law

OpenAIRE

David D. Friedman; William M. Landes; Richard A. Posner

1991-01-01

Despite the practical importance of trade secrets to the business community, the law of trade secrets is a neglected orphan in economic analysis. This paper sketches an approach to the economics of trade secret law that connects it more closely both to other areas of intellectual property and to broader issues in the positive economic theory of the common law.

Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

Science.gov (United States)

Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

2016-08-25

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

SALMON SOFT ROE DNA ON BLOOD CELLS SECRETION OF CYTOKINES IN HEALTHY DONORS

Directory of Open Access Journals (Sweden)

L. N. Fedjanina

2005-01-01

Full Text Available Abstract. Salmon soft roe DNA influence on healthy donors blood cells secretion of early hemopoietic factors (IL-3, GM-CSF, TNFα as well as biologically active substance influence on cytokine balance of Тh1 and Тh2 responses (IFNγ, IL-10 in vitro was studied. It is established, that DNA has modulatory effect on secretion of all investigated cytokines - IL-3, GM-CSF, TNFα, INFγ and IL-10 by blood cells of healthy donors, increases their initially low concentration, reduces initially high and does not have essential influence at an average level of their secretion. Under action of DNA IFNγ level (stimulation index=3,3 increases more significantly than IL-10 level (stimulation index =1,9. Thus, salmon soft roe DNA possesses immunomodulatory properties.

Unconventional Pathways of Secretion Contribute to Inflammation

Directory of Open Access Journals (Sweden)

Michael J. D. Daniels

2017-01-01

Full Text Available In the conventional pathway of protein secretion, leader sequence-containing proteins leave the cell following processing through the endoplasmic reticulum (ER and Golgi body. However, leaderless proteins also enter the extracellular space through mechanisms collectively known as unconventional secretion. Unconventionally secreted proteins often have vital roles in cell and organism function such as inflammation. Amongst the best-studied inflammatory unconventionally secreted proteins are interleukin (IL-1β, IL-1α, IL-33 and high-mobility group box 1 (HMGB1. In this review we discuss the current understanding of the unconventional secretion of these proteins and highlight future areas of research such as the role of nuclear localisation.

Proton pump inhibitors inhibit pancreatic secretion

DEFF Research Database (Denmark)

Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

2015-01-01

+/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

Hoopoes color their eggs with antimicrobial uropygial secretions

Science.gov (United States)

Soler, Juan J.; Martín-Vivaldi, M.; Peralta-Sánchez, J. M.; Arco, L.; Juárez-García-Pelayo, N.

2014-09-01

Uropygial gland secretions are used as cosmetics by some species of birds to color and enhance properties of feathers and teguments, which may signal individual quality. Uropygial secretions also reach eggshells during incubation and, therefore, may influence the coloration of birds' eggs, a trait that has attracted the attention of evolutionary biologists for more than one century. The color of hoopoe eggs typically changes along incubation, from bluish-gray to greenish-brown. Here, we test experimentally the hypothesis that dark uropygial secretion of females is responsible for such drastic color change. Moreover, since uropygial secretion of hoopoes has antimicrobial properties, we also explore the association between color and antimicrobial activity of the uropygial secretion of females. We found that eggs stayed bluish-gray in nests where female access to the uropygial secretion was experimentally blocked. Furthermore, experimental eggs that were maintained in incubators and manually smeared with uropygial secretion experienced similar color changes that naturally incubated eggs did, while control eggs that were not in contact with the secretions did not experience such color changes. All these results strongly support the hypothesis that female hoopoes use their uropygial gland secretion to color the eggs. Moreover, saturation of the uropygial secretion was associated with antimicrobial activity against Bacillus licheniformis. Given the known antimicrobial potential of uropygial secretions of birds, this finding opens the possibility that in scenarios of sexual selection, hoopoes in particular and birds in general signal antimicrobial properties of their uropygial secretion by mean of changes in egg coloration along incubation.

On the Ergodic Secret-Key Agreement over Spatially Correlated Multiple-Antenna Channels with Public Discussion

KAUST Repository

Zorgui, Marwen

2015-09-28

We consider secret-key agreement with public discussion over multiple-input multiple-output (MIMO) Rayleigh fast-fading channels under correlated environment. We assume that transmit, legitimate receiver and eavesdropper antennas are correlated. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge while the transmitter has only knowledge of the correlation matrices. First, we derive the expression of the secret-key capacity under the considered setup. We prove that the optimal transmit strategy achieving the secret-key capacity consists in transmitting independent Gaussian signals along the eingenvectors of the transmit correlation matrix. The powers allocated to each channel mode are determined as the solution to a numerical optimization problem. A necessary and sufficient condition for beamforming (i.e., transmitting along the strongest channel mode) to be capacity-achieving is derived. Moreover, we analyze the impact of correlation matrices on the system performance. Finally, we study the system’s performance in the two extreme power regimes. In the high-power regime, we provide closed-form expressions of the gain/loss due to correlation. In the low signal-to-noise ratio (SNR) regime, we investigate the energy efficiency of the system by determining the minimum energy required for sharing a secret-key bit and the wideband slope while highlighting the impact of correlation matrices.

Stimulatory effect of Coca-Cola on gastroduodenal HCO3- secretion in rats.

Science.gov (United States)

Sasaki, Y; Aihara, E; Ise, F; Kita, K; Takeuchi, K

2007-10-01

We examined the effect of various carbonated beverages, especially Coca-Cola, on the HCO3- secretion in the rat stomach and duodenum. Under urethane anaesthesia, a chambered stomach or a proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The amount of CO2 contained in these beverages was about 4-7 g/mL. Coca-Cola topically applied to the mucosa for 10 min significantly increased the HCO3- secretion in both the stomach and the duodenum. The HCO3- response in the duodenum was totally abolished by indomethacin and also partially inhibited by acetazolamide, an inhibitor of carbonic anhydrase. Likewise, the response in the stomach was also markedly inhibited by either acetazolamide or indomethacin. The mucosal application of Coca-Cola increased the PGE2 contents in both the stomach and the duodenum. Other carbonated beverages, such as sparkling water, Fanta Grape or cider, also increased the HCO3- secretion in these tissues. These results suggest that Coca-Cola induces HCO3- secretion in both the stomach and the duodenum, and these responses may be attributable to both the intracellular supply of HCO3- generated via carbonic anhydrase, and endogenous PGs, probably related to the acidic pH of the solution.

Arterial stiffness and cognitive impairment.

Science.gov (United States)

Li, Xiaoxuan; Lyu, Peiyuan; Ren, Yanyan; An, Jin; Dong, Yanhong

2017-09-15

Arterial stiffness is one of the earliest indicators of changes in vascular wall structure and function and may be assessed using various indicators, such as pulse-wave velocity (PWV), the cardio-ankle vascular index (CAVI), the ankle-brachial index (ABI), pulse pressure (PP), the augmentation index (AI), flow-mediated dilation (FMD), carotid intima media thickness (IMT) and arterial stiffness index-β. Arterial stiffness is generally considered an independent predictor of cardiovascular and cerebrovascular diseases. To date, a significant number of studies have focused on the relationship between arterial stiffness and cognitive impairment. To investigate the relationships between specific arterial stiffness parameters and cognitive impairment, elucidate the pathophysiological mechanisms underlying the relationship between arterial stiffness and cognitive impairment and determine how to interfere with arterial stiffness to prevent cognitive impairment, we searched PUBMED for studies regarding the relationship between arterial stiffness and cognitive impairment that were published from 2000 to 2017. We used the following key words in our search: "arterial stiffness and cognitive impairment" and "arterial stiffness and cognitive impairment mechanism". Studies involving human subjects older than 30years were included in the review, while irrelevant studies (i.e., studies involving subjects with comorbid kidney disease, diabetes and cardiac disease) were excluded from the review. We determined that arterial stiffness severity was positively correlated with cognitive impairment. Of the markers used to assess arterial stiffness, a higher PWV, CAVI, AI, IMT and index-β and a lower ABI and FMD were related to cognitive impairment. However, the relationship between PP and cognitive impairment remained controversial. The potential mechanisms linking arterial stiffness and cognitive impairment may be associated with arterial pulsatility, as greater arterial pulsatility

The role of jasmonates in floral nectar secretion.

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Venkatesan Radhika

Full Text Available Plants produce nectar in their flowers as a reward for their pollinators and most of our crops depend on insect pollination, but little is known on the physiological control of nectar secretion. Jasmonates are well-known for their effects on senescence, the development and opening of flowers and on plant defences such as extrafloral nectar. Their role in floral nectar secretion has, however, not been explored so far. We investigated whether jasmonates have an influence on floral nectar secretion in oil-seed rape, Brassica napus. The floral tissues of this plant produced jasmonic acid (JA endogenously, and JA concentrations peaked shortly before nectar secretion was highest. Exogenous application of JA to flowers induced nectar secretion, which was suppressed by treatment with phenidone, an inhibitor of JA synthesis. This effect could be reversed by additional application of JA. Jasmonoyl-isoleucine and its structural mimic coronalon also increased nectar secretion. Herbivory or addition of JA to the leaves did not have an effect on floral nectar secretion, demonstrating a functional separation of systemic defence signalling from reproductive nectar secretion. Jasmonates, which have been intensively studied in the context of herbivore defences and flower development, have a profound effect on floral nectar secretion and, thus, pollination efficiency in B. napus. Our results link floral nectar secretion to jasmonate signalling and thereby integrate the floral nectar secretion into the complex network of oxylipid-mediated developmental processes of plants.

Climate change reduces nectar secretion in two common Mediterranean plants.

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Takkis, Krista; Tscheulin, Thomas; Tsalkatis, Panagiotis; Petanidou, Theodora

2015-09-15

Global warming can lead to considerable impacts on natural plant communities, potentially inducing changes in plant physiology and the quantity and quality of floral rewards, especially nectar. Changes in nectar production can in turn strongly affect plant-pollinator interaction networks-pollinators may potentially benefit under moderate warming conditions, but suffer as resources reduce in availability as elevated temperatures become more extreme. Here, we studied the effect of elevated temperatures on nectar secretion of two Mediterranean Lamiaceae species-Ballota acetabulosa and Teucrium divaricatum. We measured nectar production (viz. volume per flower, sugar concentration per flower and sugar content per flower and per plant), number of open and empty flowers per plant, as well as biomass per flower under a range of temperatures selected ad hoc in a fully controlled climate chamber and under natural conditions outdoors. The average temperature in the climate chamber was increased every 3 days in 3 °C increments from 17.5 to 38.5 °C. Both study species showed a unimodal response of nectar production (volume per flower, sugar content per flower and per plant) to temperature. Optimal temperature for sugar content per flower was 25-26 °C for B. acetabulosa and 29-33 °C for T. divaricatum. According to our results, moderate climate warming predicted for the next few decades could benefit nectar secretion in T. divaricatum as long as the plants are not water stressed, but have a moderate negative effect on B. acetabulosa. Nevertheless, strong warming as predicted by climate change models for the end of the 21st century is expected to reduce nectar secretion in both species and can thus significantly reduce available resources for both wild bees and honeybees in Mediterranean systems. Published by Oxford University Press on behalf of the Annals of Botany Company.

Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

Science.gov (United States)

Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

2012-01-01

Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

Secret-key expansion from covert communication

Science.gov (United States)

Arrazola, Juan Miguel; Amiri, Ryan

2018-02-01

Covert communication allows the transmission of messages in such a way that it is not possible for adversaries to detect that the communication is occurring. This provides protection in situations where knowledge that two parties are talking to each other may be incriminating to them. In this work, we study how covert communication can be used for a different purpose: secret key expansion. First, we show that any message transmitted in a secure covert protocol is also secret and therefore unknown to an adversary. We then propose a covert communication protocol where the amount of key consumed in the protocol is smaller than the transmitted key, thus leading to secure secret key expansion. We derive precise conditions for secret key expansion to occur, showing that it is possible when there are sufficiently low levels of noise for a given security level. We conclude by examining how secret key expansion from covert communication can be performed in a computational security model.

Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.

Science.gov (United States)

Iser, G; Pfohl, M; Dörr, U; Weiss, E M; Seif, F J

1994-11-01

We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.

Biodiversity's big wet secret: the global distribution of marine biological records reveals chronic under-exploration of the deep pelagic ocean.

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Thomas J Webb

Full Text Available BACKGROUND: Understanding the distribution of marine biodiversity is a crucial first step towards the effective and sustainable management of marine ecosystems. Recent efforts to collate location records from marine surveys enable us to assemble a global picture of recorded marine biodiversity. They also effectively highlight gaps in our knowledge of particular marine regions. In particular, the deep pelagic ocean--the largest biome on Earth--is chronically under-represented in global databases of marine biodiversity. METHODOLOGY/PRINCIPAL FINDINGS: We use data from the Ocean Biogeographic Information System to plot the position in the water column of ca 7 million records of marine species occurrences. Records from relatively shallow waters dominate this global picture of recorded marine biodiversity. In addition, standardising the number of records from regions of the ocean differing in depth reveals that regardless of ocean depth, most records come either from surface waters or the sea bed. Midwater biodiversity is drastically under-represented. CONCLUSIONS/SIGNIFICANCE: The deep pelagic ocean is the largest habitat by volume on Earth, yet it remains biodiversity's big wet secret, as it is hugely under-represented in global databases of marine biological records. Given both its value in the provision of a range of ecosystem services, and its vulnerability to threats including overfishing and climate change, there is a pressing need to increase our knowledge of Earth's largest ecosystem.

Pancreatic bicarbonate secretion involves two proton pumps

DEFF Research Database (Denmark)

Novak, Ivana; Wang, Jing; Henriksen, Katrine L.

2011-01-01

Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium expres...

An investigation of ultramarathon-associated visual impairment.

Science.gov (United States)

Høeg, Tracy B; Corrigan, Genevieve K; Hoffman, Martin D

2015-06-01

The purpose of this study was to investigate the characteristics under which ultramarathon-associated visual impairment occurs and to seek to identify its physiological basis and risk factors. Through an online questionnaire, distributed worldwide, we obtained information from 173 self-identified ultramarathon runners who had experienced visual impairment during an ultramarathon. We attempted to characterize this vision impairment-its symptoms, duration, and the conditions under which it occurs. Select characteristics were compared with a reference group of 412 registrants of the 161-km Western States Endurance Run. Ultramarathon-associated visual impairment was typically characterized as painless clouding of vision that resolved either during (13.5%) or after racing within a median of 3.5 hours (range 0 to 48 hours) upon cessation of running. The mean (±SD) distance at which vision impairment occurred was 73±40 km, and the 161-km distance was the most frequent race distance (46.8%) in which visual impairment occurred. Visual impairment was often recurrent, with respondents reporting having it develop during a median of 2 races. Respondents with a history of refractive surgery had more episodes than those without such history (median 3.5 vs 2 episodes, P=.010). Compared with the reference group, runners with visual impairment were nearly twice as likely (23.7% vs 12.1%, Pvisual impairment typically presents as a painless clouding of vision that is self-limited but tends to recur in certain runners. Risk appears higher among those with a history of refractive surgery, which is relevant for ultramarathon runners who are considering, or who have a history of, refractive surgery. Published by Elsevier Inc.

A Genome-Wide Association Study of IVGTT-Based Measures of First Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants

DEFF Research Database (Denmark)

Wood, Andrew R; Jonsson, Anna; Jackson, Anne U

2017-01-01

Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intrav...

Effect of esophageal distention on basal and stimulated gastric acid secretion in rats

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Mohammad Kazem Gharib Nasery

2007-02-01

Full Text Available Background: It is well established that the esophageal distention leads to gastric relaxation, partly by vago-vagal reflex but till now, the effect of esophageal distention on gastric acid secretion has not been investigated. The aim of this study was to investigate the effect of esophageal distention (ED on basal and stimulated gastric acid secretion. Methods: Adult male Wistar rats (200-240g were deprived of food but not water for 24 hrs before the experiments. Under urethane anesthesia (1.2 g/kg, i.p., animals underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through duodenum for gastric distention and gastric washout and the esophagus was cannulated with a distensible balloon orally to distend esophagus (0.3 ml, 10 min. Gastric acid secretion was stimulated by gastric distention, carbachol (4 µg/kg, i.p. or histamine (5 mg/kg, s.c.. Effects of vagotomy, L-NAME (10 mg/kg, i.v., L-arginine (500 mg/kg, i.p. and hexamethonium were also investigated. Results: Esophageal distention reduces basal and gastric distention, carbachol and histamine stimulated acid secretion (P<0.05, P<0.0001, P<0.01 and P<0.02, respectively. Vagotomy reduced the inhibitory effect of the esophagus distention on gastric distention-induced acid secretion (P<0.05. Conclusion: These results indicate that vagus nerve involves in the inhibitory effect of the esophageal distention on the basal and stimulated gastric acid secretion. Nitric oxide (NO may also be involved.

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.

Science.gov (United States)

Adini, Irit; Ghosh, Kaustabh; Adini, Avner; Chi, Zai-Long; Yoshimura, Takeru; Benny, Ofra; Connor, Kip M; Rogers, Michael S; Bazinet, Lauren; Birsner, Amy E; Bielenberg, Diane R; D'Amato, Robert J

2014-01-01

Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases.

Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

Science.gov (United States)

Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

2015-12-01

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. Copyright © 2015 the American Physiological Society.

Effects of intense abdominal irradiation at a high dose (1100 rd) on gastric secretion and apparent feed digestibility in swine

International Nuclear Information System (INIS)

Daburon, F.; Tricaud, Y.; Bourhoven, D.

1980-01-01

Gastric and pancreatic secretions were studied in 8 pigs irradiated at 1100 rd on the hind-half of the body. Irradiation always caused achlorhydria lasting at least 10 days. Recovery was partial and variable; rehabilitation or the persistence of anorexia closely depended on recovery. Stomachal mucosa response to gastrin stimulation was very disturbed. Impairment of the pancreatic endocrine function led to progressive diabetes; the exocrine function also seemed to decrease with the survival time

Air Force UAV’s: The Secret History

Science.gov (United States)

2010-07-01

iA Mitchell Institute Study i Air Force UAVs The Secret History A Mitchell Institute Study July 2010 By Thomas P. Ehrhard Report Documentation Page...DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Air Force UAVs The Secret History 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c... The Secret History 2 Air Force UAVs: The Secret History2 air Force uaVs: The secret history Has any airplane in the past decade captured the public

Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

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Ina Bähr

2017-01-01

Full Text Available Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

Stimulatory effects of adenosine on prolactin secretion in the pituitary gland of the rat

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D.L.W. Picanço-Diniz

2002-07-01

Full Text Available We investigated the effects of adenosine on prolactin (PRL secretion from rat anterior pituitaries incubated in vitro. The administration of 5-N-methylcarboxamidoadenosine (MECA, an analog agonist that preferentially activates A2 receptors, induced a dose-dependent (1 nM to 1 µM increase in the levels of PRL released, an effect abolished by 1,3-dipropyl-7-methylxanthine, an antagonist of A2 adenosine receptors. In addition, the basal levels of PRL secretion were decreased by the blockade of cyclooxygenase or lipoxygenase pathways, with indomethacin and nordihydroguaiaretic acid (NDGA, respectively. The stimulatory effects of MECA on PRL secretion persisted even after the addition of indomethacin, but not of NDGA, to the medium. MECA was unable to stimulate PRL secretion in the presence of dopamine, the strongest inhibitor of PRL release that works by inducing a decrease in adenylyl cyclase activity. Furthermore, the addition of adenosine (10 nM mimicked the effects of MECA on PRL secretion, an effect that persisted regardless of the presence of LiCl (5 mM. The basal secretion of PRL was significatively reduced by LiCl, and restored by the concomitant addition of both LiCl and myo-inositol. These results indicate that PRL secretion is under a multifactorial regulatory mechanism, with the participation of different enzymes, including adenylyl cyclase, inositol-1-phosphatase, cyclooxygenase, and lipoxygenase. However, the increase in PRL secretion observed in the lactotroph in response to A2 adenosine receptor activation probably was mediated by mechanisms involving regulation of adenylyl cyclase, independent of membrane phosphoinositide synthesis or cyclooxygenase activity and partially dependent on lipoxygenase arachidonic acid-derived substances.

The type III protein secretion system contributes to Xanthomonas citri subsp. citri biofilm formation

KAUST Repository

Zimaro, Tamara

2014-04-18

Background: Several bacterial plant pathogens colonize their hosts through the secretion of effector proteins by a Type III protein secretion system (T3SS). The role of T3SS in bacterial pathogenesis is well established but whether this system is involved in multicellular processes, such as bacterial biofilm formation has not been elucidated. Here, the phytopathogen Xanthomonas citri subsp. citri (X. citri) was used as a model to gain further insights about the role of the T3SS in biofilm formation. Results: The capacity of biofilm formation of different X. citri T3SS mutants was compared to the wild type strain and it was observed that this secretion system was necessary for this process. Moreover, the T3SS mutants adhered proficiently to leaf surfaces but were impaired in leaf-associated growth. A proteomic study of biofilm cells showed that the lack of the T3SS causes changes in the expression of proteins involved in metabolic processes, energy generation, exopolysaccharide (EPS) production and bacterial motility as well as outer membrane proteins. Furthermore, EPS production and bacterial motility were also altered in the T3SS mutants. Conclusions: Our results indicate a novel role for T3SS in X. citri in the modulation of biofilm formation. Since this process increases X. citri virulence, this study reveals new functions of T3SS in pathogenesis. 2014 Zimaro et al.; licensee BioMed Central Ltd.

Glucose Toxic Effects on Granulation Tissue Productive Cells: The Diabetics’ Impaired Healing

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Jorge Berlanga-Acosta

2013-01-01

Full Text Available Type 2 diabetes mellitus is a metabolic noncommunicable disease with an expanding pandemic magnitude. Diabetes predisposes to lower extremities ulceration and impairs the healing process leading to wound chronification. Diabetes also dismantles innate immunity favoring wound infection. Amputation is therefore acknowledged as one of the disease’s complications. Hyperglycemia is the proximal detonator of systemic and local toxic effectors including proinflammation, acute-phase proteins elevation, and spillover of reactive oxygen and nitrogen species. Insulin axis deficiency weakens wounds’ anabolism and predisposes to inflammation. The systemic accumulation of advanced glycation end-products irreversibly impairs the entire physiology from cells-to-organs. These factors in concert hamper fibroblasts and endothelial cells proliferation, migration, homing, secretion, and organization of a productive granulation tissue. Diabetic wound bed may turn chronically inflammed, procatabolic, and an additional source of circulating pro-inflammatory cytokines, establishing a self-perpetuating loop. Diabetic fibroblasts and endothelial cells may bear mitochondrial damages becoming prone to apoptosis, which impairs granulation tissue cellularity and perfusion. Endothelial progenitor cells recruitment and tubulogenesis are also impaired. Failure of wound reepithelialization remains a clinical challenge while it appears to be biologically multifactorial. Ulcer prevention by primary care surveillance, education, and attention programs is of outmost importance to reduce worldwide amputation figures.

Drivers under the influence of drugs of abuse: quantification of cocaine and impaired driving.

Science.gov (United States)

Arroyo, Amparo; Sánchez, Marta; Barberia, Eneko; Barbal, Maria; Marrón, M Teresa; Mora, Agustí

2013-01-01

In recent years, the interest in oral fluid as a biological matrix has significantly increased, particularly for detecting driving under the influence of drugs. In this study, the concentration of cocaine and its relationship with clinical symptoms in drivers suspected of driving under the influence of drugs was evaluated. A total of 154 samples of oral fluid, which tested positive for cocaine in previous immunoassay screening, Cozart Drug Detector System, were confirmed using gas chromatography/mass spectrometry method. In Catalonia, during 2007-2010, there were 1791 samples positive for cocaine among a total of 3468 samples taken from drivers who tested positive for any drug of abuse. The evaluation of clinical symptoms was through a questionnaire that was filled in by the police officers who collected the samples. The mean concentration of cocaine was 4.11 mg/l and median concentration was 0.38 mg/l (range 0.01-345.64 mg/l). Clinical impairment symptoms such as motor coordination, walking, speech, mood and state of pupils were not significant. The testing of oral fluids presents fewer ethical problems than blood or urine.

A quantum secret-sharing protocol with fairness

International Nuclear Information System (INIS)

Liu, Feng; Qin, Su-Juan; Wen, Qiao-Yan

2014-01-01

A quantum secret-sharing (QSS) protocol consists of two main phases, called sharing and reconstruction. In the first phase, the dealer selects a secret, divides it into several shares, and sends each participant its share securely with a quantum channel. In the second phase, the participants run an interactive protocol in order to reconstruct the secret. If the participants can communicate via a broadcast channel, they can show their shares and learn the secrets simultaneously. So what happens if the channel is not simultaneous? In this paper, we propose a QSS protocol with cheaters by using partially and maximally entangled states. A secure and fair reconstruction mechanism is designed, in a way that each participant can learn or cannot learn the secret simultaneously. (papers)

Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

International Nuclear Information System (INIS)

Batzri, S.; Catravas, G.

1988-01-01

We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig

Roles of Acyl-CoA:Diacylglycerol Acyltransferases 1 and 2 in Triacylglycerol Synthesis and Secretion in Primary Hepatocytes.

Science.gov (United States)

Li, Chen; Li, Lena; Lian, Jihong; Watts, Russell; Nelson, Randal; Goodwin, Bryan; Lehner, Richard

2015-05-01

Very low-density lipoprotein assembly and secretion are regulated by the availability of triacylglycerol. Although compelling evidence indicates that the majority of triacylglycerol in very low-density lipoprotein is derived from re-esterification of lipolytic products released by endoplasmic reticulum-associated lipases, little is known about roles of acyl-CoA:diacylglycerol acyltransferases (DGATs) in this process. We aimed to investigate the contribution of DGAT1 and DGAT2 in lipid metabolism and lipoprotein secretion in primary mouse and human hepatocytes. We used highly selective small-molecule inhibitors of DGAT1 and DGAT2, and we tracked storage and secretion of lipids synthesized de novo from [(3)H]acetic acid and from exogenously supplied [(3)H]oleic acid. Inactivation of individual DGAT activity did not affect incorporation of either radiolabeled precursor into intracellular triacylglycerol, whereas combined inactivation of both DGATs severely attenuated triacylglycerol synthesis. However, inhibition of DGAT2 augmented fatty acid oxidation, whereas inhibition of DGAT1 increased triacylglycerol secretion, suggesting preferential channeling of separate DGAT-derived triacylglycerol pools to distinct metabolic pathways. Inactivation of DGAT2 impaired cytosolic lipid droplet expansion, whereas DGAT1 inactivation promoted large lipid droplet formation. Moreover, inactivation of DGAT2 attenuated expression of lipogenic genes. Finally, triacylglycerol secretion was significantly reduced on DGAT2 inhibition without altering extracellular apolipoprotein B levels. Our data suggest that DGAT1 and DGAT2 can compensate for each other to synthesize triacylglycerol, but triacylglycerol synthesized by DGAT1 is preferentially channeled to oxidation, whereas DGAT2 synthesizes triacylglycerol destined for very low-density lipoprotein assembly. © 2015 American Heart Association, Inc.

Effect of the crude extract of Eugenia uniflora in morphogenesis and secretion of hydrolytic enzymes in Candida albicans from the oral cavity of kidney transplant recipients.

Science.gov (United States)

Silva-Rocha, Walicyranison Plinio; de Brito Lemos, Vitor Luiz; Ferreira, Magda Rhayanny Assunção; Soares, Luiz Alberto Lira; Svidzisnki, Terezinha Inês Estivalet; Milan, Eveline Pipolo; Chaves, Guilherme Maranhão

2015-02-05

Candida albicans is a diploid yeast that in some circumstances may cause oral or oropharyngeal infections. Yeasts virulence factors contribute for both the maintenance of colonizing strains in addition to damage and cause tissue invasion, thus the establishment of infection occurs. The limited arsenal of antifungal drugs for the treatment of candidiasis turn the investigation of natural products mandatory for the discovery of new targets for antifungal drug development. Therefore, tropical countries emerge as important providers of natural products with potential antimicrobial activity. This study aimed to investigate morphogenesis and secretion of hydrolytic enzymes (phospholipase and proteinase) in the presence of the CE of Eugenia uniflora. The isolates were tested for their ability to form hyphae in both solid and liquid media under three different conditions: YPD + 20% FBS, Spider medium and GlcNac and the ability to secrete phospholipase and proteinase in the presence of 2000 μg/mL of E. uniflora. The CE of E. uniflora inhibited hypha formation in both liquid and solid media tested. It also impaired hydrolytic enzymes production. This was the first study to describe the interaction of a natural product with the full expression of three different factors in C. albicans. E. uniflora may be an alternative therapeutic for oral candidiasis in the future.

Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2 leading to cell depolarization and calcium influx

DEFF Research Database (Denmark)

Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Hartmann, Bolette

2015-01-01

of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide......, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose...

Proteomic identification of secreted proteins of Propionibacterium acnes

Directory of Open Access Journals (Sweden)

Holland Carsten

2010-08-01

Full Text Available Abstract Background The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that resides preferentially within sebaceous follicles; however, it also exhibits many traits of an opportunistic pathogen, playing roles in a variety of inflammatory diseases such as acne vulgaris. To date, the underlying disease-causing mechanisms remain ill-defined and knowledge of P. acnes virulence factors remains scarce. Here, we identified proteins secreted during anaerobic cultivation of a range of skin and clinical P. acnes isolates, spanning the four known phylogenetic groups. Results Culture supernatant proteins of P. acnes were separated by two-dimensional electrophoresis (2-DE and all Coomassie-stained spots were subsequently identified by MALDI mass spectrometry (MALDI-MS. A set of 20 proteins was secreted in the mid-exponential growth phase by the majority of strains tested. Functional annotation revealed that many of these common proteins possess degrading activities, including glycoside hydrolases with similarities to endoglycoceramidase, β-N-acetylglucosaminidase and muramidase; esterases such as lysophospholipase and triacylglycerol lipase; and several proteases. Other secreted factors included Christie-Atkins-Munch-Petersen (CAMP factors, glyceraldehyde 3-phosphate dehydrogenase (GAPDH, and several hypothetical proteins, a few of which are unique to P. acnes. Strain-specific differences were apparent, mostly in the secretion of putative adhesins, whose genes exhibit variable phase variation-like sequence signatures. Conclusions Our proteomic investigations have revealed that the P. acnes secretome harbors several proteins likely to play a role in host-tissue degradation and inflammation. Despite a large overlap between the secretomes of all four P. acnes phylotypes, distinct differences between predicted host-tissue interacting proteins were identified, providing potential insight into the differential virulence

Nature of altered growth hormone secretion in hyperthyroidism.

Science.gov (United States)

Iranmanesh, A; Lizarralde, G; Johnson, M L; Veldhuis, J D

1991-01-01

Hyperthyroidism is accompanied by various neuroendocrine regulatory disturbances that affect not only the thyrotropic, but also the gonadotropic, corticotropic, and somatotropic axes. To examine the nature of alterations in neuroendocrine control mechanisms that direct the somatotropic axis in hyperthyroidism, we have applied a novel deconvolution technique designed to estimate the number, amplitude, and mass of significant underlying GH secretory events after the influence of GH metabolic clearance has been removed mathematically. To this end, blood was sampled at 10-min intervals for 24 h in seven hyperthyroid and seven age-matched euthyroid men. The subsequent GH time series were assayed by immunoradiometric assay (sensitivity, 0.08 ng/mL) and submitted to quantitative deconvolution analysis. We found that hyperthyroid compared to euthyroid men 1) had significantly more GH secretory bursts per 24 h (viz. 15 +/- 1.0 vs. 10 +/- 1.1; P = 0.017); 2) secreted 3 times as much GH per burst (3.7 +/- 0.80 vs. 1.3 +/- 0.42 ng/mL distribution vol; P = 0.013); 3) achieved a maximal rate of GH secretion in each burst 2.3-fold higher than that in control men (0.14 +/- 0.028 vs. 0.060 +/- 0.015 ng/mL.min; P = 0.017); and 4) had 3.7-fold higher 24-h endogenous GH production rates (P less than 0.01). Neither hyperthyroid nor euthyroid men had significant interburst (tonic) GH secretion. We conclude that the somatotropic axis in hyperthyroid men is marked by a higher frequency of spontaneous GH secretory bursts, a higher rate of maximal GH secretion attained per burst, and a larger mass of GH released per burst. These neuroregulatory disturbances result in a nearly 4-fold increase in the 24-h production rate of GH in thyrotoxicosis.

Trade secrets protection mode of nuclear power plant

International Nuclear Information System (INIS)

Zeng Bin

2015-01-01

The paper analyzes the legal environment in which nuclear power enterprises are stayed, and mainly discusses the business secret protection modes of China's nuclear power enterprises. It is expected to provide a revelation and help for these enterprises to protect their business secrets. Firstly, the paper briefly expounds the legal basis of business secret protection and China's legalization status in this regard. Then it mainly puts forward the business secret management framework and postulations for nuclear power enterprises, and key points in application and protection of nuclear power business secret. (author)

Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

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Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

2013-01-01

The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

Right anterior temporal lobe dysfunction underlies theory of mind impairments in semantic dementia.

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Irish, Muireann; Hodges, John R; Piguet, Olivier

2014-04-01

Semantic dementia is a progressive neurodegenerative disorder characterized by the amodal and profound loss of semantic knowledge attributable to the degeneration of the left anterior temporal lobe. Although traditionally conceptualized as a language disorder, patients with semantic dementia display significant alterations in behaviour and socioemotional functioning. Recent evidence points to an impaired capacity for theory of mind in predominantly left-lateralized cases of semantic dementia; however, it remains unclear to what extent semantic impairments contribute to these deficits. Further the neuroanatomical signature of such disturbance remains unknown. Here, we sought to determine the neural correlates of theory of mind performance in patients with left predominant semantic dementia (n=11), in contrast with disease-matched cases with behavioural-variant frontotemporal dementia (n=10) and Alzheimer's disease (n=10), and healthy older individuals (n=14) as control participants. Participants completed a simple cartoons task, in which they were required to describe physical and theory of mind scenarios. Irrespective of subscale, patients with semantic dementia exhibited marked impairments relative to control subjects; however, only theory of mind deficits persisted when we covaried for semantic comprehension. Voxel-based morphometry analyses revealed that atrophy in right anterior temporal lobe structures, including the right temporal fusiform cortex, right inferior temporal gyrus, bilateral temporal poles and amygdalae, correlated significantly with theory of mind impairments in the semantic dementia group. Our results point to the marked disruption of cognitive functions beyond the language domain in semantic dementia, not exclusively attributable to semantic processing impairments. The significant involvement of right anterior temporal structures suggests that with disease evolution, the encroachment of pathology into the contralateral hemisphere heralds the

Potassium transport of Salmonella is important for type III secretion and pathogenesis

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Liu, Yehao; Ho, Katharina Kim; Su, Jing; Gong, Hao; Chang, Alexander C.

2013-01-01

Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K+), sodium ion (Na+) and proton (H+) are involved in nearly all aspects of bacterial growth and survival. K+ is the most abundant cation and its homeostasis in Escherichia coli and Salmonella is regulated by three major K+ transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of Escherichia coli; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the Salmonella K+ transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of Salmonella pathogenicity island 1 (SPI-1). Here we further explore the role of Salmonella cation transport in virulence in vitro and pathogenesis in animal models. Impairment of K+ transport through deletion of K+ transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K+ transporters are critical to the pathogenesis of Salmonella in mice and chicks and are involved in multiple growth and virulence characteristics in vitro, including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium Salmonella, especially K+ transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria. PMID:23728623

How to Split a Shared Secret into Shared Bits in Constant-Round

DEFF Research Database (Denmark)

Damgård, Ivan Bjerre; Fitzi, Matthias; Nielsen, Jesper Buus

$ such that $l = \\lceil \\log_2(p) \\rceil$, $a_0, \\ldots, a_{l-1} \\in \\{0,1\\}$ and $a = \\sum_{i=0}^{l-1} a_i 2^i$. Our protocol is secure against active adversaries and works for any linear secret sharing scheme with a multiplication protocol. This result immediately implies solutions to other long-standing open...... problems, such as constant-round and unconditionally secure protocols for comparing shared numbers and deciding whether a shared number is zero. The complexity of our protocol is $O(l \\log(l))$ invocations of the multiplication protocol for the underlying secret sharing scheme, carried out in $O(1)$....

Ionizing radiation in secret services' conspirative actions

International Nuclear Information System (INIS)

Vogel, H.; Lotz, P.; Vogel, B.

2007-01-01

Introduction: The death of Litvinenko has been reported by the media. It has raised the question whether this case had been unique. The fall of the wall has allowed a glimpse in the planning and comporting of a secret service. Material and method: Documents of the secret service of the former German democratic republic (GDR), books of defectors, and media reports about secret service actions with radiating substances have been analyzed. Results: Since decades, secret services have been using radioactive nuclides and radiation for their tasks. Several killings with radiation have been reported. A complicated logistic had been developed. Conclusion: Only singular cases of the employment of radiating substances have become known. It is probable that the majority rests unknown. Government support seems necessary in secret services' conspirative actions with radiating substance

Nutrient Impaired 303(d) Streams for the Pacific Northwest

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Department of the Interior — “Under section 303(d) of the 1972 Clean Water Act, states, territories, and authorized tribes are required to develop lists of impaired waters. These impaired waters...

Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets

International Nuclear Information System (INIS)

Douillet, Christelle; Currier, Jenna; Saunders, Jesse; Bodnar, Wanda M.; Matoušek, Tomáš; Stýblo, Miroslav

2013-01-01

Epidemiologic evidence has linked chronic exposure to inorganic arsenic (iAs) with an increased prevalence of diabetes mellitus. Laboratory studies have identified several mechanisms by which iAs can impair glucose homeostasis. We have previously shown that micromolar concentrations of arsenite (iAs III ) or its methylated trivalent metabolites, methylarsonite (MAs III ) and dimethylarsinite (DMAs III ), inhibit the insulin-activated signal transduction pathway, resulting in insulin resistance in adipocytes. Our present study examined effects of the trivalent arsenicals on insulin secretion by intact pancreatic islets isolated from C57BL/6 mice. We found that 48-hour exposures to low subtoxic concentrations of iAs III , MAs III or DMAs III inhibited glucose-stimulated insulin secretion (GSIS), but not basal insulin secretion. MAs III and DMAs III were more potent than iAs III as GSIS inhibitors with estimated IC 50 ≤ 0.1 μM. The exposures had little or no effects on insulin content of the islets or on insulin expression, suggesting that trivalent arsenicals interfere with mechanisms regulating packaging of the insulin transport vesicles or with translocation of these vesicles to the plasma membrane. Notably, the inhibition of GSIS by iAs III , MAs III or DMAs III could be reversed by a 24-hour incubation of the islets in arsenic-free medium. These results suggest that the insulin producing pancreatic β-cells are among the targets for iAs exposure and that the inhibition of GSIS by low concentrations of the methylated metabolites of iAs may be the key mechanism of iAs-induced diabetes. - Highlights: ► Trivalent arsenicals inhibit glucose stimulated insulin secretion by pancreatic islets. ► MAs III and DMAs III are more potent inhibitors than arsenite with IC 50 ∼ 0.1 μM. ► The arsenicals have little or no effects on insulin expression in pancreatic islets. ► The inhibition of insulin secretion by arsenite, MAs III or DMAs III is reversible. ► Thus

Preservation of a lower bound of quantum secret key rate in the presence of decoherence

Energy Technology Data Exchange (ETDEWEB)

Datta, Shounak, E-mail: shounak.datta@bose.res.in; Goswami, Suchetana, E-mail: suchetana.goswami@bose.res.in; Pramanik, Tanumoy, E-mail: tanu.pram99@bose.res.in; Majumdar, A.S., E-mail: archan@bose.res.in

2017-03-11

It is well known that the interaction of quantum systems with the environment reduces the inherent quantum correlations. Under special circumstances the effect of decoherence can be reversed, for example, the interaction modelled by an amplitude damping channel can boost the teleportation fidelity from the classical to the quantum region for a bipartite quantum state. Here, we first show that this phenomenon fails to preserve the quantum secret key rate derived under individual attack. We further show that the technique of weak measurement can be used to slow down the process of decoherence, thereby helping to preserve the quantum secret key rate when one or both systems are interacting with the environment via an amplitude damping channel. Most interestingly, in certain cases weak measurement with post-selection where one considers both success and failure of the technique is shown to be more useful than without it when both systems interact with the environment. - Highlights: • In general, decoherence has negative effect on the steerability and quantum secret key rate of a bipartite state. • Quantum key rate can be preserved against the effect of decoherence using the technique of weak measurement. • The technique of weak measurements includes a weak measurement and its reversal. • For some strength of weak measurement and environmental interaction, the average secret key rate is improved.

Preservation of a lower bound of quantum secret key rate in the presence of decoherence

International Nuclear Information System (INIS)

Datta, Shounak; Goswami, Suchetana; Pramanik, Tanumoy; Majumdar, A.S.

2017-01-01

It is well known that the interaction of quantum systems with the environment reduces the inherent quantum correlations. Under special circumstances the effect of decoherence can be reversed, for example, the interaction modelled by an amplitude damping channel can boost the teleportation fidelity from the classical to the quantum region for a bipartite quantum state. Here, we first show that this phenomenon fails to preserve the quantum secret key rate derived under individual attack. We further show that the technique of weak measurement can be used to slow down the process of decoherence, thereby helping to preserve the quantum secret key rate when one or both systems are interacting with the environment via an amplitude damping channel. Most interestingly, in certain cases weak measurement with post-selection where one considers both success and failure of the technique is shown to be more useful than without it when both systems interact with the environment. - Highlights: • In general, decoherence has negative effect on the steerability and quantum secret key rate of a bipartite state. • Quantum key rate can be preserved against the effect of decoherence using the technique of weak measurement. • The technique of weak measurements includes a weak measurement and its reversal. • For some strength of weak measurement and environmental interaction, the average secret key rate is improved.

Cognitive impairment in methadone maintenance patients.

Science.gov (United States)

Mintzer, Miriam Z; Stitzer, Maxine L

2002-06-01

Few well-controlled studies have examined psychomotor and cognitive performance in methadone maintenance patients (MMP). In the present study, performance of 18 opioid-dependent MMP was evaluated relative to that of 21 control participants without substance abuse histories. The MMP and control groups were balanced with respect to gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. Participants with a urine screen positive for benzodiazepines or a breathalyzer test positive for alcohol prior to performance testing were excluded. To avoid testing under conditions of acute heroin or cocaine intoxication, but without testing under conditions of acute withdrawal, participants with current use of heroin or cocaine were only required to abstain for 24 h prior to performance testing. MMP exhibited impairment relative to controls in psychomotor speed (digit symbol substitution and trail-making tests), working memory (two-back task), decision making (gambling task), and metamemory (confidence ratings on a recognition memory test); results also suggested possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP did not exhibit impairment in time estimation, conceptual flexibility or long-term memory. The wide range of impaired functions is striking, and may have important implications for daily functioning in MMP. Further research is necessary to determine the clinical significance of the impairments in laboratory-based tests for daily performance in the natural environment, as well as to differentiate impairments due to acute methadone dosing, chronic methadone maintenance, chronic poly-drug abuse, and other factors. Copyright 2002 Elsevier Science Irealnd Ltd.

Regulation of glucagon secretion by incretins

DEFF Research Database (Denmark)

Holst, Jens Juul; Christensen, M; Lund, A

2011-01-01

Glucagon secretion plays an essential role in the regulation of hepatic glucose production, and elevated fasting and postprandial plasma glucagon concentrations in patients with type 2 diabetes (T2DM) contribute to their hyperglycaemia. The reason for the hyperglucagonaemia is unclear, but recent...... studies have shown lack of suppression after oral but preserved suppression after isoglycaemic intravenous glucose, pointing to factors from the gut. Gastrointestinal hormones that are secreted in response to oral glucose include glucagon-like peptide-1 (GLP-1) that strongly inhibits glucagon secretion......, and GLP-2 and GIP, both of which stimulate secretion. When the three hormones are given together on top of isoglycaemic intravenous glucose, glucagon suppression is delayed in a manner similar to that observed after oral glucose. Studies with the GLP-1 receptor antagonist, exendin 9-39, suggest...

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes

DEFF Research Database (Denmark)

Hulman, Adam; Simmons, Rebecca K; Brunner, Eric J

2017-01-01

AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South...... Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. METHODS: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose...... (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during...

Role of adipose secreted factors and kisspeptin in the metabolic control of gonadotropin secretion and puberty

Science.gov (United States)

Factors secreted by adipose tissue continue to be discovered. Evidence indicates a strong link between neural influences and adipocyte expression and secretion of a wide array of cytokines, neurotrophic factors, growth factors, binding proteins, and neuropeptides. These “adipokines” are linked to im...

Burkholderia cenocepacia type VI secretion system mediates escape of type II secreted proteins into the cytoplasm of infected macrophages.

Directory of Open Access Journals (Sweden)

Roberto Rosales-Reyes

Full Text Available Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (BcCVs resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1β secretion and pyroptosis. Moreover, IL-1β secretion by B. cenocepacia-infected macrophages is suppressed in deletion mutants unable to produce functional Type VI, Type IV, and Type 2 secretion systems (SS. We provide evidence that the T6SS mediates the disruption of the BcCV membrane, which allows the escape of proteins secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for efficient IL-1β secretion in a T6SS dependent manner. ZmpA and ZmpB are also required for the maturation arrest of the BcCVs and bacterial intra-macrophage survival in a T6SS-independent fashion. Our results uncover a novel mechanism for inflammasome activation that involves cooperation between two bacterial secretory pathways, and an unanticipated role for T2SS-secreted proteins in intracellular bacterial survival.

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors

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Rui Hao

2017-10-01

Full Text Available Brain-derived neurotrophic factor (BDNF is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNFMet/Met mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/Met mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.

H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.

Science.gov (United States)

Takeuchi, Koji; Ise, Fumitaka; Takahashi, Kento; Aihara, Eitaro; Hayashi, Shusaku

2015-04-30

Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

Visualization of glucagon secretion from pancreatic α cells by bioluminescence video microscopy: Identification of secretion sites in the intercellular contact regions

International Nuclear Information System (INIS)

Yokawa, Satoru; Suzuki, Takahiro; Inouye, Satoshi; Inoh, Yoshikazu; Suzuki, Ryo; Kanamori, Takao; Furuno, Tadahide; Hirashima, Naohide

2017-01-01

We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion. From immunochemical analyses, PGCG-GLase stably expressed in clonal αTC1.6 cells was correctly processed and released by secretory granules. Luminescence signals of the secreted PGCG-GLase from the stable cells were visualized by video-rate bioluminescence microscopy. The video images showed an increase in glucagon secretion from clustered cells in response to stimulation by KCl. The secretory events were observed frequently at the intercellular contact regions. Thus, the localization and frequency of glucagon secretion might be regulated by cell-cell adhesion. - Highlights: • The fused protein of proglucagon to Gaussia luciferase was used as a reporter. • The fusion protein was highly expressed using a preferred human-codon optimized gene. • Glucagon secretion stimulated by depolarization was determined by luminescence. • Glucagon secretion in α cells was visualized by bioluminescence imaging. • Glucagon secretion sites were localized in the intercellular contact regions.

29 CFR 1903.9 - Trade secrets.

Science.gov (United States)

2010-07-01

... INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All... concerns or relates to the trade secrets, processes, operations, style of work, or apparatus, or to the...

Men Are from Mars, Women Are from Venus: Sex Differences in Insulin Action and Secretion.

Science.gov (United States)

Basu, Ananda; Dube, Simmi; Basu, Rita

2017-01-01

Sex difference plays a substantial role in the regulation of glucose metabolism in healthy glucose-tolerant humans. The factors which may contribute to the sex-related differences in glucose metabolism include differences in lifestyle (diet and exercise), sex hormones, and body composition. Several epidemiological and observational studies have noted that impaired glucose tolerance is more common in women than men. Some of these studies have attributed this to differences in body composition, while others have attributed impaired insulin sensitivity as a cause of impaired glucose tolerance in women. We studied postprandial glucose metabolism in 120 men and 90 women after ingestion of a mixed meal. Rates of meal glucose appearance, endogenous glucose production, and glucose disappearance were calculated using a novel triple-tracer isotope dilution method. Insulin action and secretion were calculated using validated physiological models. While rate of meal glucose appearance was higher in women than men, rates of glucose disappearance were higher in elderly women than elderly men while young women had lower rates of glucose disappearance than young men. Hence, sex has an impact on postprandial glucose metabolism, and sex differences in carbohydrate metabolism may have important implications for approaches to prevent and manage diabetes in an individual.

Air Force UAVs: The Secret History

Science.gov (United States)

2010-07-01

iA Mitchell Institute Study i Air Force UAVs The Secret History A Mitchell Institute Study July 2010 By Thomas P. Ehrhard Report Documentation Page...DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Air Force UAVs The Secret History 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...opening phases of Operation Enduring Freedom in Afghanistan. By Thomas P. Ehrhard a miTchEll insTiTuTE sTudy July 2010 Air Force UAVs The Secret History

Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance.

Directory of Open Access Journals (Sweden)

Songyan Wang

Full Text Available We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP on insulin secretion rates (ISRs and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans.

THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

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Dusik eKim

2014-06-01

Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent control of overnight ACTH secretion.

Science.gov (United States)

Iranmanesh, Ali; Veldhuis, Johannes D

2008-11-01

ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Seven healthy men. An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by >or=77 and 54% respectively (Pfeedforward coordination. The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging.

The ESX system in Bacillus subtilis mediates protein secretion.

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Laura A Huppert

Full Text Available Esat-6 protein secretion systems (ESX or Ess are required for the virulence of several human pathogens, most notably Mycobacterium tuberculosis and Staphylococcus aureus. These secretion systems are defined by a conserved FtsK/SpoIIIE family ATPase and one or more WXG100 family secreted substrates. Gene clusters coding for ESX systems have been identified amongst many organisms including the highly tractable model system, Bacillus subtilis. In this study, we demonstrate that the B. subtilis yuk/yue locus codes for a nonessential ESX secretion system. We develop a functional secretion assay to demonstrate that each of the locus gene products is specifically required for secretion of the WXG100 virulence factor homolog, YukE. We then employ an unbiased approach to search for additional secreted substrates. By quantitative profiling of culture supernatants, we find that YukE may be the sole substrate that depends on the FtsK/SpoIIIE family ATPase for secretion. We discuss potential functional implications for secretion of a unique substrate.

Distillation of secret-key from a class of compound memoryless quantum sources

Energy Technology Data Exchange (ETDEWEB)

Boche, H., E-mail: boche@tum.de; Janßen, G., E-mail: gisbert.janssen@tum.de [Lehrstuhl für Theoretische Informationstechnik, Technische Universität München, 80290 München (Germany)

2016-08-15

We consider secret-key distillation from tripartite compound classical-quantum-quantum (cqq) sources with free forward public communication under strong security criterion. We design protocols which are universally reliable and secure in this scenario. These are shown to achieve asymptotically optimal rates as long as a certain regularity condition is fulfilled by the set of its generating density matrices. We derive a multi-letter formula which describes the optimal forward secret-key capacity for all compound cqq sources being regular in this sense. We also determine the forward secret-key distillation capacity for situations where the legitimate sending party has perfect knowledge of his/her marginal state deriving from the source statistics. In this case regularity conditions can be dropped. Our results show that the capacities with and without the mentioned kind of state knowledge are equal as long as the source is generated by a regular set of density matrices. We demonstrate that regularity of cqq sources is not only a technical but also an operational issue. For this reason, we give an example of a source which has zero secret-key distillation capacity without sender knowledge, while achieving positive rates is possible if sender marginal knowledge is provided.

Rhizomucor miehei triglyceride lipase is processed and secreted from transformed Aspergillus oryzae.

Science.gov (United States)

Huge-Jensen, B; Andreasen, F; Christensen, T; Christensen, M; Thim, L; Boel, E

1989-09-01

The cDNA encoding the precursor of the Rhizomucor miehei triglyceride lipase was inserted in an Aspergillus oryzae expression vector. In this vector the expression of the lipase cDNA is under control of the Aspergillus oryzae alpha-amylase gene promoter and the Aspergillus niger glucoamylase gene terminator. The recombinant plasmid was introduced into Aspergillus oryzae, and transformed colonies were selected and screened for lipase expression. Lipase-positive transformants were grown in a small fermentor, and recombinant triglyceride lipase was purified from the culture broth. The purified enzymatically active recombinant lipase (rRML) secreted from A. oryzae was shown to have the same characteristics with respect to mobility on reducing SDS-gels and amino acid composition as the native enzyme. N-terminal amino acid sequencing indicated that approximately 70% of the secreted rRML had the same N-terminal sequence as the native Rhizomucor miehei enzyme, whereas 30% of the secreted rRML was one amino acid residue shorter in the N-terminal. The recombinant lipase precursor, which has a 70 amino acid propeptide, is thus processed in and secreted from Aspergillus oryzae. We have hereby demonstrated the utility of this organism as a host for the production of recombinant triglyceride lipases.

Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

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Takayoshi eUbuka

2013-03-01

Full Text Available Seasonally breeding birds detect environmental signals, such as light, temperature, food availability and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH, activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH, inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction.

Effects of lethal over-exposure on gastric secretion in the pig

International Nuclear Information System (INIS)

Remy, J.; Daburon, F.; Villiers, P.A.; Dubedat, P.

1975-01-01

The characteristics of gastric secretion following acute γ exposure (1,500 rd) were studied in pigs with a small Pavlov stomach. Spontaneous secretion was practically inhibited when the animals were taken out of the irradiation cell. It slowly recovered in the following hours and its pH, first neutral, turned acid again. However, till the third day, it did not recover normal characteristics. The excretion of sodium ions was much increased. Under histaminic stimulation, the responses of irradiated pigs and controls were much similar. The secretory capacities of the gastric mucosa were retained but without spontaneous manifestations. As a conclusion, the early troubles following overexposure must be the consequences of regulation disorders rather than of the direct action of radiation on the stomach. (orig.) [de

Regulation of melatonin secretion in the pineal organ of the domestic duck--an in vitro study.

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Prusik, M; Lewczuk, B; Ziółkowska, N; Przybylska-Gornowicz, B

2015-01-01

The aim of study was to determine the mechanisms regulating melatonin secretion in the pineal organs of 1-day-old and 9-month-old domestic ducks. The pineals were cultured in a superfusion system under different light conditions. Additionally, some explants were treated with norepinephrine. The pineal glands of 1-day-old ducks released melatonin in a well-entrained, regular rhythm during incubation under a 12 hrs light:12 hrs dark cycle and adjusted their secretory activity to a reversed 12 hrs dark:12 hrs light cycle within 2 days. In contrast, the diurnal changes in melatonin secretion from the pineals of 9-month-old ducks were largely irregular and the adaptation to a reversed cycle lasted 3 days. The pineal organs of nestling and adult ducks incubated in a continuous light or darkness secreted melatonin in a circadian rhythm. The treatment with norepinephrine during photophases of a light-dark cycle resulted in: 1) a precise adjustment of melatonin secretion rhythm to the presence of this catecholamine in the culture medium, 2) a very high amplitude of the rhythm, 3) a rapid adaptation of the pineal secretory activity to a reversed light-dark cycle. The effects of norepinephrine were similar in the pineal organs of nestlings and adults. In conclusion, melatonin secretion in the duck pineal organ is controlled by three main mechanisms: the direct photoreception, the endogenous generator and the noradrenergic transmission. The efficiency of intra-pineal, photosensitivity-based regulatory mechanism is markedly lower in adult than in nestling individuals.

Extrafloral nectar secretion from wounds of Solanum dulcamara.

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Lortzing, Tobias; Calf, Onno W; Böhlke, Marlene; Schwachtje, Jens; Kopka, Joachim; Geuß, Daniel; Kosanke, Susanne; van Dam, Nicole M; Steppuhn, Anke

2016-04-25

Plants usually close wounds rapidly to prevent infections and the loss of valuable resources such as assimilates(1). However, herbivore-inflicted wounds on the bittersweet nightshade Solanum dulcamara appear not to close completely and produce sugary wound secretions visible as droplets. Many plants across the plant kingdom secrete sugary nectar from extrafloral nectaries(2) to attract natural enemies of herbivores for indirect defence(3,4). As ants forage on wound edges of S. dulcamara in the field, we hypothesized that wound secretions are a form of extrafloral nectar (EFN). We show that, unlike EFN from known nectaries, wound secretions are neither associated with any specific structure nor restricted to certain locations. However, similar to EFN, they are jasmonate-inducible and the plant controls their chemical composition. Wound secretions are attractive for ants, and application of wound secretion mimics increases ant attraction and reduces herbivory on S. dulcamara plants in a natural population. In greenhouse experiments, we reveal that ants can defend S. dulcamara from two of its native herbivores, slugs and flea beetle larvae. Since nectar is defined by its ecological function as a sugary secretion involved in interactions with animals(5), such 'plant bleeding' could be a primitive mode of nectar secretion exemplifying an evolutionary origin of structured extrafloral nectaries.

Incretin hormone secretion over the day

DEFF Research Database (Denmark)

Ahren, B; Carr, RD; Deacon, Carolyn F.

2010-01-01

The two incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are key factors in the regulation of islet function and glucose metabolism, and incretin-based therapy for type 2 diabetes has gained considerable interest during recent years. Regulat......The two incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are key factors in the regulation of islet function and glucose metabolism, and incretin-based therapy for type 2 diabetes has gained considerable interest during recent years....... Regulation of incretin hormone secretion is less well characterized. The main stimulus for incretin hormone secretion is presence of nutrients in the intestinal lumen, and carbohydrate, fat as well as protein all have the capacity to stimulate GIP and GLP-1 secretion. More recently, it has been established...... that a diurnal regulation exists with incretin hormone secretion to an identical meal being greater when the meal is served in the morning compared to in the afternoon. Finally, whether incretin hormone secretion is altered in disease states is an area with, so far, controversial results in different studies...

Exosome secretion affects social motility in Trypanosoma brucei.

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Dror Eliaz

2017-03-01

Full Text Available Extracellular vesicles (EV secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB utilizing the endosomal sorting complexes required for transport (ESCRT, through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo. This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites.

Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

Science.gov (United States)

Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

2017-09-01

Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

Reappraisal of bicarbonate secretion by the human oesophagus

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, J; Bukhave, Klaus

1997-01-01

BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosalbicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophagealbicarbonate secretion and thus......: The median rates (95% confidence intervals)of intrinsic oesophageal bicarbonate secretion, corrected for contaminating salivary and gastric bicarbonate, were 89 (33-150) and 121 (63-203)mumol/h/10 cm (p > 0.5) in omeprazole and ranitidine treated subjects respectively. Salivary and gastric bicarbonate...... be overestimated. As omeprazole and ranitidine did not affect bicarbonate secretion differently there was no evidence that omeprazole acts on icarbonate secretory cells in the oesophageal mucosa....

Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

1995-01-01

BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal...... healthy volunteers. Bicarbonate and PGE2 were measured in the gastroduodenal effluents by back-titration and radioimmunoassay, respectively. RESULTS: Vagal stimulation and duodenal luminal acidification (0.1 M HCl; 20 ml; 5 min) increased gastroduodenal bicarbonate secretion (p ... markedly inhibited both basal and stimulated gastric and duodenal mucosal bicarbonate secretion, and this reduction was similar to the degree of cyclooxygenase inhibition estimated by the luminal release of PGE2 (p

[Secret drug tribulations and French legislation].

Science.gov (United States)

Charlot, Colette

2002-01-01

From an official Montpellier prefecture paper of 18th century, we are interested in a secret drug from Provence origin: the Irroë powder. This purgative will pass from "secret" drug status to "patent" drug. It's notoriety will come from its arrival to Paris. The law of 21th germinal year XI, the decret of 25 prairial year XIII and this of 18th 1810 imposed to give the drug composition to an official status; that examined and permit it's sale. This secret will be produce for half century.

Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

International Nuclear Information System (INIS)

Ramasharma, K.; Li, C.H.

1987-01-01

Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction.

Science.gov (United States)

Brownfoot, Fiona C; Hastie, Roxanne; Hannan, Natalie J; Cannon, Ping; Tuohey, Laura; Parry, Laura J; Senadheera, Sevvandi; Illanes, Sebastian E; Kaitu'u-Lino, Tu'uhevaha J; Tong, Stephen

2016-03-01

explant-conditioned media (to whole vessels). Finally, we examined the effects of metformin on angiogenesis on maternal omental vessel explants. Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary endothelial cells, villous cytotrophoblast cells, and preterm preeclamptic placental villous explants. The reduction in soluble fms-like tyrosine kinase 1 and soluble endoglin secretion was rescued by coadministration of succinate, which suggests that the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin were likely to be regulated at the level of the mitochondria. In addition, the mitochondrial electron transport chain inhibitors rotenone and antimycin reduced soluble fms-like tyrosine kinase 1 secretion, which further suggests that soluble fms-like tyrosine kinase 1 secretion is regulated through the mitochondria. Mitochondrial electron transport chain activity in preterm preeclamptic placentas was increased compared with gestation-matched control subjects. Metformin improved features of endothelial dysfunction relevant to preeclampsia. It reduced endothelial cell messenger RNA expression of vascular cell adhesion molecule 1 that was induced by tumor necrosis factor-α (vascular cell adhesion molecule 1 is an inflammatory adhesion molecule up-regulated with endothelial dysfunction and is increased in preeclampsia). Placental conditioned media impaired bradykinin-induced vasodilation; this effect was reversed by metformin. Metformin also improved whole blood vessel angiogenesis impaired by fms-like tyrosine kinase 1. Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary human tissues, possibly by inhibiting the mitochondrial electron transport chain. The activity of the mitochondrial electron transport chain was increased in preterm preeclamptic placenta. Metformin reduced endothelial dysfunction, enhanced vasodilation in omental arteries, and induced

SECURE VISUAL SECRET SHARING BASED ON DISCRETE WAVELET TRANSFORM

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S. Jyothi Lekshmi

2015-08-01

Full Text Available Visual Cryptography Scheme (VCS is an encryption method to encode secret written materials. This method converts the secret written material into an image. Then encode this secret image into n shadow images called shares. For the recreation of the original secret, all or some selected subsets of shares are needed; individual shares are of no use on their own. The secret image can be recovered simply by selecting some subset of these n shares, makes transparencies of them and stacking on top of each other. Nowadays, the data security has an important role. The shares can be altered by an attacker. So providing security to the shares is important. This paper proposes a method of adding security to cryptographic shares. This method uses two dimensional discrete wavelet transform to hide visual secret shares. Then the hidden secrets are distributed among participants through the internet. All hidden shares are extracted to reconstruct the secret.

On Secret Sharing with Nonlinear Product Reconstruction

DEFF Research Database (Denmark)

Cascudo Pueyo, Ignacio; Cramer, Ronald; Mirandola, Diego

2015-01-01

Multiplicative linear secret sharing is a fundamental notion in the area of secure multiparty computation and, since recently, in the area of two-party cryptography as well. In a nutshell, this notion guarantees that the product of two secrets is obtained as a linear function of the vector......-necessarily-linear “product reconstruction function.” Is the resulting notion equivalent to multiplicative linear secret sharing? We show the (perhaps somewhat counterintuitive) result that this relaxed notion is strictly more general. Concretely, fix a finite field ${\\mathbb F}_q$ as the base field over which linear secret...... sharing is considered. Then we show there exists an (exotic) linear secret sharing scheme with an unbounded number of players $n$ such that it has $t$-privacy with $t = \\Omega(n)$ and such that it does admit a product reconstruction function, yet this function is necessarily nonlinear. In addition, we...

Reelin secreted by GABAergic neurons regulates glutamate receptor homeostasis.

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Cecilia Gonzalez Campo

Full Text Available BACKGROUND: Reelin is a large secreted protein of the extracellular matrix that has been proposed to participate to the etiology of schizophrenia. During development, reelin is crucial for the correct cytoarchitecture of laminated brain structures and is produced by a subset of neurons named Cajal-Retzius. After birth, most of these cells degenerate and reelin expression persists in postnatal and adult brain. The phenotype of neurons that bind secreted reelin and whether the continuous secretion of reelin is required for physiological functions at postnatal stages remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Combining immunocytochemical and pharmacological approaches, we first report that two distinct patterns of reelin expression are present in cultured hippocampal neurons. We show that in hippocampal cultures, reelin is secreted by GABAergic neurons displaying an intense reelin immunoreactivity (IR. We demonstrate that secreted reelin binds to receptors of the lipoprotein family on neurons with a punctate reelin IR. Secondly, using calcium imaging techniques, we examined the physiological consequences of reelin secretion blockade. Blocking protein secretion rapidly and reversibly changes the subunit composition of N-methyl-D-aspartate glutamate receptors (NMDARs to a predominance of NR2B-containing NMDARs. Addition of recombinant or endogenously secreted reelin rescues the effects of protein secretion blockade and reverts the fraction of NR2B-containing NMDARs to control levels. Therefore, the continuous secretion of reelin is necessary to control the subunit composition of NMDARs in hippocampal neurons. CONCLUSIONS/SIGNIFICANCE: Our data show that the heterogeneity of reelin immunoreactivity correlates with distinct functional populations: neurons synthesizing and secreting reelin and/or neurons binding reelin. Furthermore, we show that continuous reelin secretion is a strict requirement to maintain the composition of NMDARs. We propose

Melatonin Secretion Pattern in Critically Ill Patients

DEFF Research Database (Denmark)

Boyko, Yuliya; Holst, René; Jennum, Poul

2017-01-01

effect of remifentanil on melatonin secretion. We found that the risk of atypical sleep compared to normal sleep was significantly lower (p REM) sleep was only observed during the nonsedation period. We found preserved diurnal pattern of melatonin...... secretion in these patients. Remifentanil did not affect melatonin secretion but was associated with lower risk of atypical sleep pattern. REM sleep was only registered during the period of nonsedation.......Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin...

Thymidine secretion by hybridoma and myeloma cells

International Nuclear Information System (INIS)

Spilsberg, Bjorn; Rise, Frode; Petersen, Dirk; Nissen-Meyer, Jon

2006-01-01

Secretion of thymidine appeared to be a common property of hybridoma and myeloma cells, but not of other cell types, which were tested. Of three hybridoma cell lines tested, all secreted thymidine in amounts resulting in the accumulation of thymidine to concentrations of 10-20 μM in the culture medium. Also three of five myeloma cell lines that were analyzed secrete thymidine, but none of the other cell types that were studied. Thymidine was purified to homogeneity (4 mg purified from 3 l of culture medium) and identified as such by nuclear magnetic resonance spectroscopy. The cells that secreted thymidine showed high resistance to the growth inhibitory effect of thymidine

Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice.

Science.gov (United States)

Song 宋志林, Zhilin; Roncal-Jimenez, Carlos A; Lanaspa-Garcia, Miguel A; Oppelt, Sarah A; Kuwabara, Masanari; Jensen, Thomas; Milagres, Tamara; Andres-Hernando, Ana; Ishimoto, Takuji; Garcia, Gabriela E; Johnson, Ginger; MacLean, Paul S; Sanchez-Lozada, Laura-Gabriela; Tolan, Dean R; Johnson, Richard J

2017-02-01

Fructose stimulates vasopressin in humans and can be generated endogenously by activation of the polyol pathway with hyperosmolarity. We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration. Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired. This study increases our understanding of the

A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion.

Science.gov (United States)

Scott, Niv; Prigge, Matthias; Yizhar, Ofer; Kimchi, Tali

2015-09-24

It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex-specific manner. In females, ablating the AVPV TH(+) neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH(+) neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH(+) neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour.

Getting in and Getting On? The Experiences of Young People with Visual Impairments and Hearing Impairments in Third-Level Education

Science.gov (United States)

Byrne, Bronagh

2014-01-01

Young disabled people continue to be under-represented throughout further and higher education settings. Drawing on Pierre Bourdieu's social theory of habitus, capital and field, this paper explores the practices of domination and oppression that have made it difficult for young people with visual impairments and hearing impairments to participate…

Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

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Sebastian Gehmert

2014-01-01

Full Text Available Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs, these cells (ASCs provide a therapeutic option for Duchenne Muscular Dystrophy (DMD. But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases.

Intermittent subglottic secretion drainage may cause tracheal damage in patients with few oropharyngeal secretions.

Science.gov (United States)

Suys, E; Nieboer, K; Stiers, W; De Regt, J; Huyghens, L; Spapen, H

2013-12-01

Injurious prolapse of tracheal mucosa into the suction port has been reported in up to 50% of intubated patients receiving continuous aspiration of subglottic secretions. We investigated whether similar injury could be inflicted by automated intermittent aspiration. Six consecutive patients, intubated with the Mallinckrodt TaperGuard Evac™ endotracheal tube, were studied. A flow sensor was placed between the vacuum regulating system and the mucus collector. Intermittent suctioning was performed at a pressure of -125 mmHg with a 25s interval and duration of 15s. After 24h, a CT scan of the tracheal region was performed. Excessive negative suction pressure, a fast drop in aspiration flow to zero, and important "swinging" movements of secretions in the evacuation line were observed in all patients. Oral instillation of antiseptic mouthwash restored normal aspiration flow and secretion mobility. CT imaging showed marked entrapment of tracheal mucosa into the suction port in all patients. In patients with few oropharyngeal secretions, automated intermittent subglottic aspiration may result in significant and potential harmful invagination of tracheal mucosa into the suction lumen. A critical amount of fluid must be present in the oropharynx to assure adequate and safe aspiration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantitative proteomics unravels that the post-transcriptional regulator Crc modulates the generation of vesicles and secreted virulence determinants of Pseudomonas aeruginosa.

Science.gov (United States)

Reales-Calderón, Jose Antonio; Corona, Fernando; Monteoliva, Lucía; Gil, Concha; Martínez, Jose Luis

2015-09-08

Recent research indicates that the post-transcriptional regulator Crc modulates susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Several P. aeruginosa virulence factors are secreted or engulfed in vesicles. To decipher the Crc modulation of P. aeruginosa virulence, we constructed a crc deficient mutant and measure the proteome associated extracellular vesicles and the vesicle-free secretome using iTRAQ. Fifty vesicle-associated proteins were more abundant and 14 less abundant in the crc-defective strain, whereas 37 were more abundant and 17 less abundant in the vesicle-free secretome. Among them, virulence determinants, such as ToxA, protease IV, azurin, chitin-binding protein, PlcB and Hcp1, were less abundant in the crc-defective mutant. Transcriptomic analysis revealed that some of the observed changes were post-transcriptional and, thus, could be attributed to a direct Crc regulatory role; whereas, for other differentially secreted proteins, the regulatory role was likely indirect. We also observed that the crc mutant presented an impaired vesicle-associated secretion of quorum sensing signal molecules and less cytotoxicity than its wild-type strain. Our results offer new insights into the mechanisms by which Crc regulates P. aeruginosa virulence, through the modulation of vesicle formation and secretion of both virulence determinants and quorum sensing signals. This article is part of a Special Issue entitled: HUPO 2014. Published by Elsevier B.V.

Sagnac secret sharing over telecom fiber networks.

Science.gov (United States)

Bogdanski, Jan; Ahrens, Johan; Bourennane, Mohamed

2009-01-19

We report the first Sagnac quantum secret sharing (in three-and four-party implementations) over 1550 nm single mode fiber (SMF) networks, using a single qubit protocol with phase encoding. Our secret sharing experiment has been based on a single qubit protocol, which has opened the door to practical secret sharing implementation over fiber telecom channels and in free-space. The previous quantum secret sharing proposals were based on multiparticle entangled states, difficult in the practical implementation and not scalable. Our experimental data in the three-party implementation show stable (in regards to birefringence drift) quantum secret sharing transmissions at the total Sagnac transmission loop distances of 55-75 km with the quantum bit error rates (QBER) of 2.3-2.4% for the mean photon number micro?= 0.1 and 1.7-2.1% for micro= 0.3. In the four-party case we have achieved quantum secret sharing transmissions at the total Sagnac transmission loop distances of 45-55 km with the quantum bit error rates (QBER) of 3.0-3.7% for the mean photon number micro= 0.1 and 1.8-3.0% for micro?= 0.3. The stability of quantum transmission has been achieved thanks to our new concept for compensation of SMF birefringence effects in Sagnac, based on a polarization control system and a polarization insensitive phase modulator. The measurement results have showed feasibility of quantum secret sharing over telecom fiber networks in Sagnac configuration, using standard fiber telecom components.

Analysis of secreted proteins from Aspergillus flavus.

Science.gov (United States)

Medina, Martha L; Haynes, Paul A; Breci, Linda; Francisco, Wilson A

2005-08-01

MS/MS techniques in proteomics make possible the identification of proteins from organisms with little or no genome sequence information available. Peptide sequences are obtained from tandem mass spectra by matching peptide mass and fragmentation information to protein sequence information from related organisms, including unannotated genome sequence data. This peptide identification data can then be grouped and reconstructed into protein data. In this study, we have used this approach to study protein secretion by Aspergillus flavus, a filamentous fungus for which very little genome sequence information is available. A. flavus is capable of degrading the flavonoid rutin (quercetin 3-O-glycoside), as the only source of carbon via an extracellular enzyme system. In this continuing study, a proteomic analysis was used to identify secreted proteins from A. flavus when grown on rutin. The growth media glucose and potato dextrose were used to identify differentially expressed secreted proteins. The secreted proteins were analyzed by 1- and 2-DE and MS/MS. A total of 51 unique A. flavus secreted proteins were identified from the three growth conditions. Ten proteins were unique to rutin-, five to glucose- and one to potato dextrose-grown A. flavus. Sixteen secreted proteins were common to all three media. Fourteen identifications were of hypothetical proteins or proteins of unknown functions. To our knowledge, this is the first extensive proteomic study conducted to identify the secreted proteins from a filamentous fungus.

control of acid secretion i the surgery of duode al ulcer

African Journals Online (AJOL)

course of treatment which temporarily heals the ulcer is not always sufficient to ... be based on the acid output of the resting and active stomach, the length of history of ... average night secretion of 60 mEq. had, after vagotomy, an average free ...... project under the auspices of the National Cancer Association of. South Africa ...

Secret-key rates and privacy leakage in biometric systems

NARCIS (Netherlands)

Ignatenko, T.

2009-01-01

In this thesis both the generation of secret keys from biometric data and the binding of secret keys to biometric data are investigated. These secret keys can be used to regulate access to sensitive data, services, and environments. In a biometric secrecy system a secret key is generated or chosen

Analysis of an acyl-CoA binding protein in Aspergillus oryzae that undergoes unconventional secretion.

Science.gov (United States)

Kwon, Hee Su; Kawaguchi, Kouhei; Kikuma, Takashi; Takegawa, Kaoru; Kitamoto, Katsuhiko; Higuchi, Yujiro

2017-11-04

Acyl-CoA binding protein (ACBP) plays important roles in the metabolism of lipids in eukaryotic cells. In the industrially important filamentous fungus Aspergillus oryzae, although we have previously demonstrated that the A. oryzae ACBP (AoACBP) localizes to punctate structures and exhibits long-range motility, which is dependent on autophagy-related proteins, the physiological role of AoACBP remains elusive. Here, we describe identification and characterization of another ACBP from A. oryzae; we named this ACBP as AoAcb2 and accordingly renamed AoACBP as AoAcb1. The deduced amino acid sequence of AoAcb2 lacked a signal peptide. Phylogenetic analysis classified AoAcb2 into a clade that was same as the ACBP Acb1 of the model yeast Saccharomyces cerevisiae, but was different from that of AoAcb1. In contrast to punctate localization of AoAcb1, AoAcb2 was found to be dispersedly distributed in the cytoplasm, as was previously observed for the S. cerevisiae Acb1. Since we could not generate an Aoacb2 disruptant, we created an Aoacb2 conditional mutant that exhibited less growth under Aoacb2-repressed condition, suggesting that Aoacb2 is an essential gene for growth. Moreover, we observed that A. oryzae AoAcb2, but not A. oryzae AoAcb1, was secreted under carbon-starved condition, suggesting that AoAcb2 might be secreted via the unconventional protein secretion (UPS) pathway, just like S. cerevisiae Acb1. We also demonstrated that the unconventional secretion of AoAcb2 was dependent on the t-SNARE AoSso1, but was independent of the autophagy-related protein AoAtg1, suggesting that the unconventional secretion of AoAcb2, unlike that of S. cerevisiae Acb1, via the UPS pathway, is not regulated by the autophagy machinery. Thus, the filamentous fungus A. oryzae harbors two types of ACBPs, one of which appears to be essential for growth and undergoes unconventional secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

Stereotype threat can both enhance and impair older adults' memory.

Science.gov (United States)

Barber, Sarah J; Mather, Mara

2013-12-01

Negative stereotypes about aging can impair older adults' memory via stereotype threat; however, the mechanisms underlying this phenomenon are unclear. In two experiments, we tested competing predictions derived from two theoretical accounts of stereotype threat: executive-control interference and regulatory fit. Older adults completed a working memory test either under stereotype threat about age-related memory declines or not under such threat. Monetary incentives were manipulated such that recall led to gains or forgetting led to losses. The executive-control-interference account predicts that stereotype threat decreases the availability of executive-control resources and hence should impair working memory performance. The regulatory-fit account predicts that threat induces a prevention focus, which should impair performance when gains are emphasized but improve performance when losses are emphasized. Results were consistent only with the regulatory-fit account. Although stereotype threat significantly impaired older adults' working memory performance when remembering led to gains, it significantly improved performance when forgetting led to losses.

Pituitary-hormone secretion by thyrotropinomas

OpenAIRE

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

2008-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore ev...

Peptides and neurotransmitters that affect renin secretion

Science.gov (United States)

Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

1984-01-01

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

Insulin Secretion and Incretin Hormone Concentration in Women with Previous Gestational Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Sung Hoon Yu

2011-02-01

Full Text Available BackgroundWe examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide 1 (GLP-1 on insulin secretion in women with previous gestational diabetes (pGDM.MethodsA 75-g oral glucose tolerance test (OGTT was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured.ResultsAmong 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT.ConclusionGLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes.

Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid.

Science.gov (United States)

Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

2017-04-05

Sea buckthorn ( Hippophae rhamnoides ) -derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

Directory of Open Access Journals (Sweden)

Shigeru Nakamura

2017-04-01

Full Text Available Sea buckthorn (Hippophae rhamnoides–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1, a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

Shigella IpaD has a dual role: signal transduction from the type III secretion system needle tip and intracellular secretion regulation.

Science.gov (United States)

Roehrich, A Dorothea; Guillossou, Enora; Blocker, Ariel J; Martinez-Argudo, Isabel

2013-02-01

Type III secretion systems (T3SSs) are protein injection devices essential for the interaction of many Gram-negative bacteria with eukaryotic cells. While Shigella assembles its T3SS when the environmental conditions are appropriate for invasion, secretion is only activated after physical contact with a host cell. First, the translocators are secreted to form a pore in the host cell membrane, followed by effectors which manipulate the host cell. Secretion activation is tightly controlled by conserved T3SS components: the needle tip proteins IpaD and IpaB, the needle itself and the intracellular gatekeeper protein MxiC. To further characterize the role of IpaD during activation, we combined random mutagenesis with a genetic screen to identify ipaD mutant strains unable to respond to host cell contact. Class II mutants have an overall defect in secretion induction. They map to IpaD's C-terminal helix and likely affect activation signal generation or transmission. The Class I mutant secretes translocators prematurely and is specifically defective in IpaD secretion upon activation. A phenotypically equivalent mutant was found in mxiC. We show that IpaD and MxiC act in the same intracellular pathway. In summary, we demonstrate that IpaD has a dual role and acts at two distinct locations during secretion activation. © 2013 Blackwell Publishing Ltd.

Histaminergic regulation of prolactin secretion

DEFF Research Database (Denmark)

Knigge, U P

1990-01-01

Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following...... systemic infusion of the amine. In addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1-receptors, while following systemic...... administration this effect is mediated via H2-receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional...

An unexpected knock on Corrigan's secret door.

Science.gov (United States)

Woywodt, Alexander

2010-10-01

Corrigan's secret door describes a metaphorical escape route for busy physicians. The term was derived from the successful and exceptionally busy professional life of Irish physician Dominic John Corrigan (1802-80). It is claimed that Corrigan's outpatient clinic was so busy that he required a secret door in his consulting rooms to escape from the ever-growing queue of eager patients. The origins of this charming story are unknown, and the door may have never existed. However, at present, Corrigan's secret door is often quoted when busy physicians have their own little ways in surviving a stressful professional life. Generations of British-trained doctors have grown up with Corrigan's secret door, as it was featured in the introduction of the Oxford Handbook of Clinical Medicine. Accordingly, trainees as well as more senior doctors are often reminded that having a 'secret door' is vital in surviving in the medical profession. My own escape is through classical music and the violoncello, in particular. As the name implies, my own secret door is normally invisible to colleagues and patients. This little article is about a patient who found me out, and a reflection on the role of classical music and the cello in my professional life.

Secrets and Disclosures: How Young Children Handle Secrets

Science.gov (United States)

Anagnostaki, Lida; Wright, Michael J.; Papathanasiou, Athanasia

2013-01-01

The authors examined the influence of content and verbal cues on young children's understanding of secret information and of its disclosure. Participants were 209 5- and 6-year-old children in an experiment where a puppet, named Zinc, was the protagonist. Children were asked to whom Zinc would disclose a list of pieces of information, some of…

Does impaired socioemotional functioning account for behavioral dysexecutive disorders? Evidence from a transnosological study.

Science.gov (United States)

Narme, Pauline; Roussel, Martine; Mouras, Harold; Krystkowiak, Pierre; Godefroy, Olivier

2017-01-01

Behavioral dysexecutive disorders are highly prevalent in patients with neurological diseases but cannot be explained by cognitive dysexecutive impairments. In fact, the underlying mechanisms are poorly understood. Given that socioemotional functioning underlies appropriate behavior, socioemotional impairments may contribute to the appearance of behavioral disorders. To investigate this issue, we performed a transnosological study. Seventy-five patients suffering from various neurological diseases (Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration, and stroke) were included in the study. The patients were comprehensively assessed in terms of cognitive and behavioral dysexecutive disorders and socioemotional processes (facial emotion recognition and theory of mind). As was seen for cognitive and behavioral dysexecutive impairments, the prevalence of socioemotional impairments varied according to the diagnosis. Stepwise logistic regressions showed that (i) only cognitive executive indices predicted hypoactivity with apathy/abulia, (ii) theory of mind impairments predicted hyperactivity-distractibility-impulsivity and stereotyped/perseverative behaviors, and (iii) impaired facial emotion recognition predicted social behavior disorders. Several dysexecutive behavioral disorders are associated with an underlying impairment in socioemotional processes but not with cognitive indices of executive functioning (except for apathy). These results strongly suggest that some dysexecutive behavioral disorders are the outward signs of an underlying impairment in socioemotional processes.

Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

OpenAIRE

Nakamura, Shigeru; Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

2017-01-01

Sea buckthorn (Hippophae rhamnoides)–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, pr...

The Criminalization of the Theft of Trade Secrets:\\ud An Analysis of the Economic Espionage Act

OpenAIRE

Searle, Nicola

2012-01-01

This paper presents a law and economics assessment of how the elevation of the theft of trade secrets from civil malfeasance to a felony affects the incentives for both firms and potential thieves. The paper begins with theoretical analysis of the EEA and concludes with an empirical assessment of prosecutions under the EEA. In comparison to penalties used in civil cases, the new incentive of a criminal deterrent to trade secret theft introduces severe consequences, such as incarceration as a ...

Low cost of gastric acid secretion during digestion in ball pythons.

Science.gov (United States)

Nørgaard, Simon; Andreassen, Kim; Malte, Christian Lind; Enok, Sanne; Wang, Tobias

2016-04-01

Due to their large metabolic responses to digestion (specific dynamic action, SDA), snakes represent an interesting animal group to identify the underlying mechanisms for the postprandial rise in metabolism. The SDA response results from the energetic costs of many different processes ranging over prey handling, secretions by the digestive system, synthesis of enzymes, plasticity of most visceral organs, as well as protein synthesis and nitrogen excretion. The contribution of the individual mechanisms, however, remains elusive. Gastric acid secretion has been proposed to account for more than half of the SDA response, while other studies report much lower contributions of the gastric processes. To investigate the energetic cost of gastric acid secretion, ball pythons (Python regius) were fed meals with added amounts of bone meal (up to 25 g bone meal kg(-1) snake) to achieve a five-fold rise in the buffer capacity of the meals. Direct measurements within the stomach lumen showed similar reduction in gastric pH when buffer capacity was increased, but we found no effects on the rise in oxygen consumption over the first three days of digestion. There was, however, a slower return of oxygen consumption to resting baseline. We conclude that gastric acid secretion only contributes modestly to the SDA response and propose that post-absorptive processes, such as increased protein synthesis, are likely to underlie the SDA response. Copyright © 2016 Elsevier Inc. All rights reserved.

VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

International Nuclear Information System (INIS)

Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica; Gonzalez Espinosa, Claudia

2010-01-01

Research highlights: → Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. → CoCl 2 -induced VEGF secretion in mast cells occurs by a Ca 2+ -insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. → Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits FcεRI-dependent anaphylactic degranulation in mast cells. → Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl 2 ) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl 2 promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl 2 -induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl 2 -induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl 2 in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals-dependent Fyn kinase activation.

VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

Energy Technology Data Exchange (ETDEWEB)

Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico); Gonzalez Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico)

2010-10-15

Research highlights: {yields} Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. {yields} CoCl{sub 2}-induced VEGF secretion in mast cells occurs by a Ca{sup 2+}-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. {yields} Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits Fc{epsilon}RI-dependent anaphylactic degranulation in mast cells. {yields} Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl{sub 2}) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl{sub 2} promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl{sub 2}-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl{sub 2}-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl{sub 2} in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals

Regulation of atrial natriuretic peptide (ANP) secretion

International Nuclear Information System (INIS)

Ruskoaho, H.; Toth, M.; Lang, R.E.; Unger, Th.; Garten, D.

1986-01-01

To investigate the role of calcium, protein kinase C and adenylate cyclase in the ANP secretion, the secretory responses from isolated perfused rat hearts to a calcium channel activator, Bay k8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluomethylphenyl)-2-pyridine-5-carboxylate), the calcium ionophore (A23187), the phorbol ester (12-0-tetradecanoylphorbol-13-acetate, TPA), and to forskolin were studied. ANP in perfusate was measured by radioimmunoassay 10 min before and during the infusion (30 min) of various agents at 2 min intervals. A23187 (5.7 x 10 -7 ) induced a sharp increase, whereas TPA (0.15 - 1.6 x 10 -7 ) caused a slowly progressive increase in ANP secretion. 4a-phorbol-12,13-didecanoate, a non-active phorbol ester, had no effect on ANP secretion. Bay k8644 (4 x 10 -7 ) and forskolin (1 x 10 -6 ) alone caused small but sustained increase in ANP secretion. The combination of TPA with Bay k8644, forskolin or A23187 stimulated ANP secretion higher than the calculated additive value for each agent. Dibuturyl-cAMP (1.6 x 10 -4 ) pretreatment also enhanced TPA-induced ANP release. 8-Bromo-cGMP (1.3 x 10 -4 ) and sodium nitroprusside (9 x 10 -5 ) alone had no effect, but both attenuated the TPA-induced ANP secretion. The results suggest that atrial cardiocytes possess at least two different secretory pathways for ANP secretion, which are probably dependent on protein kinase C and cyclic AMP