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Sample records for increased flow mediated

  1. Patients with migraine with aura have increased flow mediated dilation

    Directory of Open Access Journals (Sweden)

    Altamura Claudia

    2010-03-01

    Full Text Available Abstract Background Endothelium-derived nitric oxide (NO mediates the arterial dilation following a flow increase (i.e. flow-mediated dilation, FMD, easily assessed in the brachial artery. NO is also involved in cerebral hemodynamics and it is supposed to trigger vascular changes occurring during migraine. This study aimed at investigating whether migraine patients present an altered response to NO also in the peripheral artery system. Methods We enrolled 21 migraineurs (10 with aura [MwA], 11 without aura [MwoA], and 13 controls. FMD was evaluated with ultrasound in all subjects by measuring the percentage increase of the brachial artery diameter induced by hyperaemia reactive to sustained cuff inflation around the arm above systolic pressure. FMD values were then normalized for shear stress. Results Normalized FMD values were higher in patients with MwA (28.5 10-2%.s than in controls (9.0 10-2%.s and patients with MwoA (13.7 10-2%.s (p Conclusions Migraineurs with aura present an excessive arterial response to hyperaemia, likely as an effect of an increased sensitivity to endothelium-derived nitric oxide. This phenomenon observed peripherally might reflect similar characteristics in the cerebral circulation.

  2. Improved brachial artery shear patterns and increased flow-mediated dilation after low-volume high-intensity interval training in type 2 diabetes.

    Science.gov (United States)

    Ghardashi Afousi, Alireza; Izadi, Mohammad Reza; Rakhshan, Kamran; Mafi, Farnoosh; Biglari, Soheil; Gandomkar Bagheri, Habibalah

    2018-06-22

    What is the central question of this study? Endothelial function is impaired because of increased oscillatory and retrograde shear in patients with type 2 diabetes. It is unclear whether low-volume high-intensity interval training and continuous moderate intensity exercise can modulate oscillatory and retrograde shear, blood flow and flow-mediated arterial dilation in these patients. What is the main finding and its importance? We found that low-volume high-intensity interval training, by increasing anterograde shear and decreasing retrograde shear and oscillatory index, can increase nitric oxide production and consequently result in increased flow-mediated dilation and outward arterial remodelling in patients with type 2 diabetes. Atherosclerosis in patients with type 2 diabetes is characterized by endothelial dysfunction associated with impaired flow-mediated dilation (FMD) and increases retrograde and oscillatory shear. The present study investigated endothelium-dependent vasodilation and shear rate in patients with type 2 diabetes at baseline and follow-up after 12 weeks of low-volume high-intensity interval training (LV-HIIT) or continuous moderate intensity training (CMIT). Seventy five sedentary patients with type 2 diabetes and untreated pre- or stage I hypertension were randomly divided into LV-HIIT, CMIT and control groups. The LV-HIIT group intervention was 12 intervals of 1.5 min at 85%-90% HR max and 2 min at 55%-60% HR max . The CMIT group intervention was 42 min of exercise at 70% HR max for 3 sessions per week during 12 weeks. High-resolution Doppler ultrasound was used to measure FMD, arterial diameter, anterograde and retrograde blood flow and shear rate patterns. Brachial artery FMD increased significantly in the LV-HIIT group (3.83 ± 1.13 baseline, 7.39 ± 3.6% follow-up), whereas there were no significant increase in the CMIT group (3.45 ± 0.97 baseline, 4.81 ± 2.36% follow-up) compared to the control group (3.16 ± 0

  3. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow

    DEFF Research Database (Denmark)

    Guan, Xinfu; Karpen, Heidi E; Stephens, John

    2006-01-01

    . These actions are mediated by the G-protein-coupled receptor, GLP-2R. Cellular localization of the GLP-2R and the nature of its signaling network in the gut, however, are poorly defined. Thus, our aim was to establish cellular localization of GLP-2R and functional connection to vascular action of GLP-2......-dependently stimulated intestinal blood flow and coordinately upregulated the expression of intestinal eNOS mRNA, protein, and phosphorylation (eNOS-Ser1117). CONCLUSIONS: We conclude that the GLP-2-induced stimulation of blood flow is mediated by vasoactive neurotransmitters that are colocalized with GLP-2R in 2...

  4. Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Theard, M A; Pelligrino, D A

    1994-01-01

    ) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

  5. Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

    Science.gov (United States)

    Feehan, Robert P.; Kunselman, Allen R.; Preston, Amy G.; Miller, Debra L.; Lott, Mary E. J.

    2011-01-01

    An inverse relation exists between intake of flavonoid-rich foods, such as cocoa, and cardiovascular-related mortality. Favorable effects of flavonoids on the endothelium may underlie these associations. We performed a randomized, double-blind, placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation, as measured by an increase in brachial artery flow-mediated dilation (FMD), in healthy older adults. Measurements were obtained before (preingestion) and after (1- and 2-h postingestion) ingestion of 0 (placebo), 2, 5, 13, and 26 g of cocoa in 23 adults (63 ± 2 yr old, mean ± SE). Changes in brachial artery FMD 1- and 2-h postingestion compared with preingestion were used to determine the effects of cocoa. FMD was unchanged 1 (Δ−0.3 ± 0.2%)- and 2-h (Δ0.1 ± 0.1%) after placebo (0 g cocoa). In contrast, FMD increased both 1-h postingestion (2 g cocoa Δ0.0 ± 0.2%, 5 g cocoa Δ0.8 ± 0.3%, 13 g cocoa Δ1.0 ± 0.3%, and 26 g cocoa Δ1.6 ± 0.3%: P FMD 1- and 2-h postingestion (r = 0.44–0.48; both P FMD in healthy older humans. These responses may help to explain associations between flavonoid intake and cardiovascular-related mortality in humans. PMID:21903881

  6. β-Receptor-mediated increase in cerebral blood flow during hypoglycemia

    International Nuclear Information System (INIS)

    Hollinger, B.R.; Bryan, R.M.

    1987-01-01

    The authors tested the hypothesis that β-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin; normoglycemic control rates were given saline. Propranolol was administered to some control and some hypoglycemic rats to block the β-adrenergic receptors. Regional CBF was measured using 4-[N-methyl- 14 C]iodoantipyrine. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from ∼60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. They conclude that β-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia

  7. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  8. Ethanol-induced increase in portal blood flow: Role of acetate and A1- and A2-adenosine receptors

    International Nuclear Information System (INIS)

    Carmichael, F.J.; Saldivia, V.; Varghese, G.A.; Israel, Y.; Orrego, H.

    1988-01-01

    The increase in portal blood flow induced by ethanol appears to be adenosine mediated. Acetate, which is released by the liver during ethanol metabolism, is known to increase adenosine levels in tissues and in blood. The effects of acetate on portal blood flow were investigated in rats using the microsphere technique. The intravenous infusion of acetate resulted in vasodilation of the preportal vasculature and in a dose-dependent increase in portal blood flow. This acetate-induced increase in portal blood flow was suppressed by the adenosine receptor blocker, 8-phenyltheophylline. Using the A 1 -adenosine receptor agonist N-6-cyclohexyl adenosine and the A 2 -agonist 5'-N-ethylcarboxamido adenosine, we demonstrate that the effect of adenosine on the preportal vasculature is mediated by the A 2 -subtype of adenosine receptors. In conclusion, these data support the hypothesis that the increase in portal blood flow after ethanol administration results from a preportal vasodilatory effect of adenosine formed from acetate metabolism in extrahepatic tissues

  9. Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Moshage, HJ; Gans, ROB

    2000-01-01

    Background Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is

  10. Polyoxometalate active charge-transfer material for mediated redox flow battery

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Travis Mark; Hudak, Nicholas; Staiger, Chad; Pratt, Harry

    2017-01-17

    Redox flow batteries including a half-cell electrode chamber coupled to a current collecting electrode are disclosed herein. In a general embodiment, a separator is coupled to the half-cell electrode chamber. The half-cell electrode chamber comprises a first redox-active mediator and a second redox-active mediator. The first redox-active mediator and the second redox-active mediator are circulated through the half-cell electrode chamber into an external container. The container includes an active charge-transfer material. The active charge-transfer material has a redox potential between a redox potential of the first redox-active mediator and a redox potential of the second redox-active mediator. The active charge-transfer material is a polyoxometalate or derivative thereof. The redox flow battery may be particularly useful in energy storage solutions for renewable energy sources and for providing sustained power to an electrical grid.

  11. TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

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    Garvin, Jeffrey L.

    2014-01-01

    Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min (n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min (P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min (P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min (P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min (P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL. PMID:24966090

  12. Effect of fructose and sucralose on flow-mediated vasodilatation in healthy, white European males

    International Nuclear Information System (INIS)

    Memon, M. Q.; Simpson, E. J.; Macdonald, I. A.

    2014-01-01

    Objective: To assess how acute consumption of fructose affects flow-mediated dilatation in brachial artery. Methods: The randomised cross-over study was conducted at the University of Nottingham's Medical School, Nottingham, United Kingdom in July 2009. Ten healthy, white European males visited the laboratory twice, on separate mornings. On each visit, the volunteers consumed water (3ml/kg body weight) and rested semi-supine on the bed. After 30 minutes, baseline diastolic brachial artery diameter and blood velocity was measured. At 60 minutes, blood velocity and five scans of brachial artery diameter were recorded before a blood pressure cuff was inflated on the forearm for 5 minutes and at 50-60-70-80 and 90 sec after cuff deflation. Fifteen minutes later, the volunteers consumed 500ml of test-drink containing either fructose (0.75 g/kg body weight) or sucralose (sweetness-matched with fructose drink); 45 minutes later, baseline and flow-mediated dilatation was re-measured. Results: Pre-drink and post-drink baseline values were similar on two occasions (p> 0.05). Brachial artery diameter increased (p < 0.05) by 7+-3% pre-fructose and by 6. 3% above baseline values post-fructose with no significant difference in these responses (p < 0.15). It increased (p < 0.05) by 5.9+-3% above baseline before and by 6.7+-2% (p < 0.01) after sucralose; a significant difference was noted in these flow-mediated dilatation responses (p < 0.02). Responses before and after sucralose were not different from those before and after fructose (p < 0.294). Conclusion: Acute ingestion of fructose or sucralose had no effect on flow-mediated dilatation measured at brachial artery. (author)

  13. Can the measurement of brachial artery flow-mediated dilation be applied to the acute exercise model?

    Directory of Open Access Journals (Sweden)

    Harris Ryan A

    2007-11-01

    Full Text Available Abstract The measurement of flow-mediated dilation using high-resolution ultrasound has been utilized extensively in interventional trials evaluating the salutary effect of drugs and lifestyle modifications (i.e. diet or exercise training on endothelial function; however, until recently researchers have not used flow-mediated dilation to examine the role of a single bout of exercise on vascular function. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables (i.e. mode, intensity, duration, etc. and permits greater experimental control of confounding variables. Given that the application of flow-mediated dilation in the acute exercise paradigm is expanding, the purpose of this review is to discuss methodological and physiological factors pertinent to flow-mediated dilation in the context of acute exercise. Although the scientific rationale for evaluating endothelial function in response to acute exercise is sound, few concerns warrant attention when interpreting flow-mediated dilation data following acute exercise. The following questions will be addressed in the present review: Does the measurement of flow-mediated dilation influence subsequent serial measures of flow-mediated dilation? Do we need to account for diurnal variation? Is there an optimal time to measure post-exercise flow-mediated dilation? Is the post-exercise flow-mediated dilation reproducible? How is flow-mediated dilation interpreted considering the hemodynamic and sympathetic changes associated with acute exercise? Can the measurement of endothelial-independent dilation affect the exercise? Evidence exists to support the methodological appropriateness for employing flow-mediated dilation in the acute exercise model; however, further research is warranted to clarify its interpretation following acute exercise.

  14. Pollen- and seed-mediated transgene flow in commercial cotton seed production fields.

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    Shannon Heuberger

    Full Text Available BACKGROUND: Characterizing the spatial patterns of gene flow from transgenic crops is challenging, making it difficult to design containment strategies for markets that regulate the adventitious presence of transgenes. Insecticidal Bacillus thuringiensis (Bt cotton is planted on millions of hectares annually and is a potential source of transgene flow. METHODOLOGY/PRINCIPAL FINDINGS: Here we monitored 15 non-Bt cotton (Gossypium hirsutum, L. seed production fields (some transgenic for herbicide resistance, some not for gene flow of the Bt cotton cry1Ac transgene. We investigated seed-mediated gene flow, which yields adventitious Bt cotton plants, and pollen-mediated gene flow, which generates outcrossed seeds. A spatially-explicit statistical analysis was used to quantify the effects of nearby Bt and non-Bt cotton fields at various spatial scales, along with the effects of pollinator abundance and adventitious Bt plants in fields, on pollen-mediated gene flow. Adventitious Bt cotton plants, resulting from seed bags and planting error, comprised over 15% of plants sampled from the edges of three seed production fields. In contrast, pollen-mediated gene flow affected less than 1% of the seed sampled from field edges. Variation in outcrossing was better explained by the area of Bt cotton fields within 750 m of the seed production fields than by the area of Bt cotton within larger or smaller spatial scales. Variation in outcrossing was also positively associated with the abundance of honey bees. CONCLUSIONS/SIGNIFICANCE: A comparison of statistical methods showed that our spatially-explicit analysis was more powerful for understanding the effects of surrounding fields than customary models based on distance. Given the low rates of pollen-mediated gene flow observed in this study, we conclude that careful planting and screening of seeds could be more important than field spacing for limiting gene flow.

  15. Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome.

    Science.gov (United States)

    Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Omori, Kazuko; Imai, Yasushi; Fujita, Daishi; Nishimura, Hiroshi; Kato, Masayoshi; Morota, Tetsuro; Nawata, Kan; Ozeki, Atsuko; Watanabe, Aya; Kawarasaki, Shuichi; Hosoya, Yumiko; Nakao, Tomoko; Maemura, Koji; Nagai, Ryozo; Hirata, Yasunobu; Komuro, Issei

    2014-07-01

    Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 ± 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 ± 1.8 versus 15.2 ± 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.

  16. Flow Giese reaction using cyanoborohydride as a radical mediator

    Directory of Open Access Journals (Sweden)

    Takahide Fukuyama

    2013-09-01

    Full Text Available Tin-free Giese reactions, employing primary, secondary, and tertiary alkyl iodides as radical precursors, ethyl acrylate as a radical trap, and sodium cyanoborohydride as a radical mediator, were examined in a continuous flow system. With the use of an automated flow microreactor, flow reaction conditions for the Giese reaction were quickly optimized, and it was found that a reaction temperature of 70 °C in combination with a residence time of 10–15 minutes gave good yields of the desired addition products.

  17. Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Theard, M A; Pelligrino, D A

    1994-01-01

    Neurons synthesize NO, which may act as a retrograde messenger, involved in either potentiating or depressing neuronal excitability. NO may also play a role in the cerebral vasodilatory response to increased neuronal activity (i.e., seizures). In this study, two questions were asked: (1) is NO an......Neurons synthesize NO, which may act as a retrograde messenger, involved in either potentiating or depressing neuronal excitability. NO may also play a role in the cerebral vasodilatory response to increased neuronal activity (i.e., seizures). In this study, two questions were asked: (1......) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

  18. A multi-electron redox mediator for redox-targeting lithium-sulfur flow batteries

    Science.gov (United States)

    Li, Guochun; Yang, Liuqing; Jiang, Xi; Zhang, Tianran; Lin, Haibin; Yao, Qiaofeng; Lee, Jim Yang

    2018-02-01

    The lithium-sulfur flow battery (LSFB) is a new addition to the rechargeable lithium flow batteries (LFBs) where sulfur or a sulfur compound is used as the cathode material against the lithium anode. We report here our evaluation of an organic sulfide - dimethyl trisulfide (DMTS), as 1) a catholyte of a LFB and 2) a multi-electron redox mediator for discharging and charging a solid sulfur cathode without any conductive additives. The latter configuration is also known as the redox-targeting lithium-sulfur flow battery (RTLSFB). The LFB provides an initial discharge capacity of 131.5 mAh g-1DMTS (1.66 A h L-1), which decreases to 59 mAh g-1DMTS (0.75 A h L-1) after 40 cycles. The RTLSFB delivers a significantly higher application performance - initial discharge capacity of 1225.3 mAh g-1sulfur (3.83 A h L-1), for which 1030.9 mAh g-1sulfur (3.23 A h L-1) is still available after 40 cycles. The significant increase in the discharge and charge duration of the LFB after sulfur addition indicates that DMTS is better used as a redox mediator in a RTLSFB than as a catholyte in a LFB.

  19. Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease

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    Noboru Toda

    2016-08-01

    Full Text Available Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic nerves and nitric oxide (NO liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS/neuronal NOS (nNOS inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD. Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD.

  20. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow

    DEFF Research Database (Denmark)

    Jensen, Elisa Pouline; Poulsen, Steen Seier; Kissow, Hannelouise

    2015-01-01

    was to localize renal GLP-1 receptors and describe GLP-1 mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using 125I-GLP-1......, 125I-exendin-4 (GLP-1 analog) and 125I-exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1 mediated effects on blood pressure (BP), renal blood flow (RBF), heart rate (HR), renin secretion, urinary flow rate and Na+ and K+ excretion were...... conclude that GLP-1 receptors are located in the renal vasculature including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases renal blood flow in normotensive rats....

  1. Assessment of Bollgard II cotton pollen mediated transgenes flow to ...

    African Journals Online (AJOL)

    Assessment of Bollgard II cotton pollen mediated transgenes flow to conventional cotton in the farming conditions of Burkina ... This has led to experiment on Bt cotton from 2003 to 2007. ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  2. Effects of dietary carbohydrate restriction versus low-fat diet on flow-mediated dilation.

    Science.gov (United States)

    Volek, Jeff S; Ballard, Kevin D; Silvestre, Ricardo; Judelson, Daniel A; Quann, Erin E; Forsythe, Cassandra E; Fernandez, Maria Luz; Kraemer, William J

    2009-12-01

    We previously reported that a carbohydrate-restricted diet (CRD) ameliorated many of the traditional markers associated with metabolic syndrome and cardiovascular risk compared with a low-fat diet (LFD). There remains concern how CRD affects vascular function because acute meals high in fat have been shown to impair endothelial function. Here, we extend our work and address these concerns by measuring fasting and postprandial vascular function in 40 overweight men and women with moderate hypertriacylglycerolemia who were randomly assigned to consume hypocaloric diets (approximately 1500 kcal) restricted in carbohydrate (percentage of carbohydrate-fat-protein = 12:59:28) or LFD (56:24:20). Flow-mediated dilation of the brachial artery was assessed before and after ingestion of a high-fat meal (908 kcal, 84% fat) at baseline and after 12 weeks. Compared with the LFD, the CRD resulted in a greater decrease in postprandial triacylglycerol (-47% vs -15%, P = .007), insulin (-51% vs -6%, P = .009), and lymphocyte (-12% vs -1%, P = .050) responses. Postprandial fatty acids were significantly increased by the CRD compared with the LFD (P = .033). Serum interleukin-6 increased significantly over the postprandial period; and the response was augmented in the CRD (46%) compared with the LFD (-13%) group (P = .038). After 12 weeks, peak flow-mediated dilation at 3 hours increased from 5.1% to 6.5% in the CRD group and decreased from 7.9% to 5.2% in the LFD group (P = .004). These findings show that a 12-week low-carbohydrate diet improves postprandial vascular function more than a LFD in individuals with atherogenic dyslipidemia.

  3. Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling.

    Science.gov (United States)

    Belcik, J Todd; Davidson, Brian P; Xie, Aris; Wu, Melinda D; Yadava, Mrinal; Qi, Yue; Liang, Sherry; Chon, Chae Ryung; Ammi, Azzdine Y; Field, Joshua; Harmann, Leanne; Chilian, William M; Linden, Joel; Lindner, Jonathan R

    2017-03-28

    Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1.3 MHz, mechanical index 1.3) was performed for 10 minutes after intravenous injection of 2×10 8 lipid microbubbles. Microvascular perfusion was evaluated by low-power contrast ultrasound perfusion imaging. In vivo muscle ATP release and in vitro ATP release from endothelial cells or erythrocytes were assessed by a luciferin-luciferase assay. Purinergic signaling pathways were assessed by studying interventions that (1) accelerated ATP degradation; (2) inhibited P2Y receptors, adenosine receptors, or K ATP channels; or (3) inhibited downstream signaling pathways involving endothelial nitric oxide synthase or prostanoid production (indomethacin). Augmentation in muscle perfusion by ultrasound cavitation was assessed in a proof-of-concept clinical trial in 12 subjects with stable sickle cell disease. Therapeutic ultrasound cavitation increased muscle perfusion by 7-fold in normal mice, reversed tissue ischemia for up to 24 hours in the murine model of peripheral artery disease, and doubled muscle perfusion in patients with sickle cell disease. Augmentation in flow extended well beyond the region of ultrasound exposure. Ultrasound cavitation produced an ≈40-fold focal and sustained increase in ATP, the source of which included both endothelial cells and erythrocytes. Inhibitory studies indicated that ATP was a critical mediator of flow augmentation that acts primarily through either P2Y receptors or adenosine produced by ectonucleotidase activity. Combined indomethacin and inhibition of

  4. Microfluidic enhancement of intramedullary pressure increases interstitial fluid flow and inhibits bone loss in hindlimb suspended mice.

    Science.gov (United States)

    Kwon, Ronald Y; Meays, Diana R; Tang, W Joyce; Frangos, John A

    2010-08-01

    Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system for generating dynamic intramedullary pressure (ImP) and IFF within the femurs of alert mice. By quantifying fluorescence recovery after photobleaching (FRAP) within individual lacunae, we show that microfluidic generation of dynamic ImP significantly increases IFF within the lacunocanalicular system. In addition, we demonstrate that dynamic pressure loading of the intramedullary compartment for 3 minutes per day significantly eliminates losses in trabecular and cortical bone mineral density in hindlimb suspended mice, enhances trabecular and cortical structural integrity, and increases endosteal bone formation rate. Unlike previously developed modalities for enhancing IFF in vivo, this is the first model that allows direct and dynamic modulation of ImP and skeletal IFF within mice. Given the large number of genetic tools for manipulating the mouse genome, this model is expected to serve as a powerful investigative tool in elucidating the role of IFF in skeletal adaptation to mechanical loading and molecular mechanisms mediating this process.

  5. Effect of carbon dioxide inhalation on pulmonary hypertension induced by increased blood flow and hypoxia

    Directory of Open Access Journals (Sweden)

    I-Chun Chuang

    2011-08-01

    Full Text Available There is now increasing evidence from the experimental and clinical setting that therapeutic hypercapnia from intentionally inspired carbon dioxide (CO2 or lower tidal volume might be a beneficial adjunct to the strategies of mechanical ventilation in critical illness. Although previous reports indicate that CO2 exerts a beneficial effect in the lungs, the pulmonary vascular response to hypercapnia under various conditions remains to be clarified. The purpose of the present study is to characterize the pulmonary vascular response to CO2 under the different conditions of pulmonary hypertension secondary to increased pulmonary blood flow and secondary to hypoxic pulmonary vasoconstriction. Isolated rat lung (n = 32 was used to study (1 the vasoactive action of 5% CO2 in either N2 (hypoxic-hypercapnia or air (normoxic-hypercapnia at different pulmonary arterial pressure levels induced by graded speed of perfusion flow and (2 the role of nitric oxide (NO in mediating the pulmonary vascular response to hypercapnia, hypoxia, and flow-associated pulmonary hypertension. The results indicated that inhaled CO2 reversed pulmonary hypertension induced by hypoxia but not by flow alteration. Endogenous NO attenuates hypoxic pulmonary vasoconstriction but does not augment the CO2-induced vasodilatation. Acute change in blood flow does not alter the endogenous NO production.

  6. Characterization of Eosinophil Adhesion to TNF-a-Activated Endothelium Under Flow Conditions: a4 Integrins Mediate Initial Attachment, and E-Selectin Mediates Rolling

    NARCIS (Netherlands)

    Ulfman, L.H.; Kuijper, P.H.M.; Linden, J.A.M. van der; Lammers, J.W.J.; Zwaginga, Jaap Jan; Koenderman, L.

    1999-01-01

    The multistep model of leukocyte adhesion reveals that selectins mediate rolling interactions and that integrins mediate firm adhesion processes. In this study, the interaction between eosinophils and TNF-a-activated HUVEC (second or third passage) was studied under flow conditions (0.8 and 3.2

  7. A control systems approach to quantify wall shear stress normalization by flow-mediated dilation in the brachial artery.

    Directory of Open Access Journals (Sweden)

    Frank C G van Bussel

    Full Text Available Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMDv to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra- and inter-session reproducibilities of two indices pFMDv and mFMDv, which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMDv indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD, the peak to baseline diameter ratio (Dpeak/Dbase, and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shearAUC or with area integrated to peak hyperemia (FMD/shearAUC_peak]. Inter-session and intra-session reproducibilities for pFMDv, mFMDv and %FMD were comparable (intra-class correlation coefficients within 0.521-0.677 range. Both pFMDv and mFMDv showed more clearly a reduction after glucose loading (reduction of ~45%, p≤0.001 than the other indices (% given are relative reductions: %FMD (~11%, p≥0.074; Dpeak/Dbase (~11%, p≥0.074; FMD/shearAUC_peak (~20%, p≥0.016 and FMD/shearAUC (~38%, p≤0.038. Further analysis indicated that wall shear stress normalization under normal (fasting conditions is already far from ideal (FMDv << 1, which (therefore does not materially change with glucose loading. Our approach might be useful in intervention studies to detect intrinsic changes in shear stress normalization performance in conduit arteries.

  8. Increased bone marrow blood flow in polycythemia vera

    International Nuclear Information System (INIS)

    Lathinen, R.; Lathinen, T.; Hyoedynmaa, S.

    1983-01-01

    Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a 133 Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these diseases. The results also suggest that in older patients the simple 133 Xe method may support the diagnosis of polycythemia vera. (orig.)

  9. Increased bone marrow blood flow in polycythemia vera

    Energy Technology Data Exchange (ETDEWEB)

    Lathinen, R.; Lathinen, T.; Hyoedynmaa, S.

    1983-01-01

    Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a /sup 133/Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these diseases. The results also suggest that in older patients the simple /sup 133/Xe method may support the diagnosis of polycythemia vera.

  10. Relation of Long-term Exposure to Air Pollution to Brachial Artery Flow-Mediated Dilation and Reactive Hyperemia

    Science.gov (United States)

    Wilker, Elissa H.; Ljungman, Petter L.; Rice, Mary B.; Kloog, Itai; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Hamburg, Naomi M.; Mittleman, Murray A.

    2014-01-01

    Long-term exposure to ambient air pollution has been associated with cardiovascular morbidity and mortality. Impaired vascular responses may in part explain these findings, but the association of such long-term exposure with measures of both conduit artery and microvascular function have not been widely reported. We evaluated the association between residential proximity to a major roadway (primary or secondary highway) and spatially resolved average fine particulate matter (PM2.5) and baseline brachial artery diameter and mean flow velocity, flow mediated dilation % and hyperemic flow velocity, in the Framingham Offspring and Third Generation Cohorts. We examined 5,112 participants (2,731 (53%) women, mean age 49±14 years). Spatially resolved average PM2.5 was associated with lower flow mediated dilation% and hyperemic flow velocity. An interquartile range difference in PM2.5 (1.99 μg/m3) was associated with −0.16% (95%CI: −0.27%, −0.05%) lower FMD% and −0.72 (95%CI: −1.38, −0.06) cm/s lower hyperemic flow velocity %. Residential proximity to a major roadway was negatively associated with flow mediated dilation %. Compared to living ≥400 m away, living <50 m from a major roadway was associated with 0.32% lower flow mediated dilation (95% confidence interval (CI): −0.58%, −0.06%), but results for hyperemic flow velocity had wide confidence intervals −0.68 cm/s (95%CI: −2.29, 0.93). In conclusion, residential proximity to a major roadway and higher levels of spatially resolved estimates of PM2.5 at participant residences are associated with impaired conduit artery and microvascular function in this large community-based cohort of middle-aged and elderly adults. PMID:24793676

  11. Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases?

    Science.gov (United States)

    Weissgerber, Tracey L

    2014-11-01

    Endothelial dysfunction is a key feature of preeclampsia and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction, and shear stimulus. This review encourages researchers to think beyond "low FMD" by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for 3 years post-partum. However, FMD returns to normal by 10 years post-partum. Studies using new protocols are needed to gain more mechanistic insight.

  12. Interactive ion-mediated sap flow regulation in olive and laurel stems: physicochemical characteristics of water transport via the pit structure.

    Science.gov (United States)

    Ryu, Jeongeun; Ahn, Sungsook; Kim, Seung-Gon; Kim, TaeJoo; Lee, Sang Joon

    2014-01-01

    Sap water is distributed and utilized through xylem conduits, which are vascular networks of inert pipes important for plant survival. Interestingly, plants can actively regulate water transport using ion-mediated responses and adapt to environmental changes. However, ionic effects on active water transport in vascular plants remain unclear. In this report, the interactive ionic effects on sap transport were systematically investigated for the first time by visualizing the uptake process of ionic solutions of different ion compositions (K+/Ca2+) using synchrotron X-ray and neutron imaging techniques. Ionic solutions with lower K+/Ca2+ ratios induced an increased sap flow rate in stems of Olea europaea L. and Laurus nobilis L. The different ascent rates of ionic solutions depending on K+/Ca2+ ratios at a fixed total concentration increases our understanding of ion-responsiveness in plants from a physicochemical standpoint. Based on these results, effective structural changes in the pit membrane were observed using varying ionic ratios of K+/Ca2+. The formation of electrostatically induced hydrodynamic layers and the ion-responsiveness of hydrogel structures based on Hofmeister series increase our understanding of the mechanism of ion-mediated sap flow control in plants.

  13. Ethanol-induced increase in portal blood glow: Role of adenosine

    International Nuclear Information System (INIS)

    Orrego, H.; Carmichael, F.J.; Saldivia, V.; Giles, H.G.; Sandrin, S.; Israel, Y.

    1988-01-01

    The mechanism by which ethanol induces an increase in portal vein blood flow was studied in rats using radiolabeled microspheres. Ethanol by gavage resulted in an increase of 50-70% in portal vein blood flow. The ethanol-induced increase in portal blood flow was suppressed by the adenosine receptor blocker 8-phenyltheophylline. By itself, 8-phenyltheophylline was without effect on cardiac output or portal blood flow. Adenosine infusion resulted in a dose-dependent increase in portal blood flow. This adenosine-induced increase in portal blood flow was inhibited by 8-phenyltheophylline in a dose-dependent manner. Both alcohol and adenosine significantly reduced preportal vascular resistance by 40% and 60%, respectively. These effects were fully suppressed by 8-phenyltheophylline. It is concluded that adenosine is a likely candidate to mediate the ethanol-induced increase in portal vein blood flow. It is suggested that an increase in circulating acetate and liver hypoxia may mediate the effects of alcohol by increasing tissue and interstitial adenosine levels

  14. Microfluidic Enhancement of Intramedullary Pressure Increases Interstitial Fluid Flow and Inhibits Bone Loss in Hindlimb Suspended Mice

    OpenAIRE

    Kwon, Ronald Y; Meays, Diana R; Tang, W Joyce; Frangos, John A

    2010-01-01

    Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system fo...

  15. I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow.

    Science.gov (United States)

    Eniola, A Omolola; Krasik, Ellen F; Smith, Lee A; Song, Gang; Hammer, Daniel A

    2005-11-01

    In their active state, beta(2)-integrins, such as LFA-1, mediate the firm arrest of leukocytes by binding intercellular adhesion molecules (ICAMs) expressed on endothelium. Although the primary function of LFA-1 is assumed to be the ability to mediate firm adhesion, recent work has shown that LFA-1 can contribute to cell tethering and rolling under hydrodynamic flow, a role previously largely attributed to the selectins. The inserted (I) domain of LFA-1 has recently been crystallized in the wild-type (wt) and locked-open conformations and has been shown to, respectively, support rolling and firm adhesion under flow when expressed in alpha(L)beta(2) heterodimers or as isolated domains on cells. Here, we report results from cell-free adhesion assays where wt I-domain-coated polystyrene particles were allowed to interact with ICAM-1-coated surfaces in shear flow. We show that wt I-domain can independently mediate the capture of particles from flow and support their rolling on ICAM-1 surfaces in a manner similar to how carbohydrate-selectin interactions mediate rolling. Adhesion is specific and blocked by appropriate antibodies. We also show that the rolling velocity of I-domain-coated particles depends on the wall shear stress in flow chamber, I-domain site density on microsphere surfaces, and ICAM-1 site density on substrate surfaces. Furthermore, we show that rolling is less sensitive to wall shear stress and ICAM-1 substrate density at high density of I-domain on the microsphere surface. Computer simulations using adhesive dynamics can recreate bead rolling dynamics and show that the mechanochemical properties of ICAM-1-I-domain interactions are similar to those of carbohydrate-selectin interactions. Understanding the biophysics of adhesion mediated by the I-domain of LFA-1 can elucidate the complex roles this integrin plays in leukocyte adhesion in inflammation.

  16. Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure.

    Science.gov (United States)

    Marcus, Noah J; Pügge, Carolin; Mediratta, Jai; Schiller, Alicia M; Del Rio, Rodrigo; Zucker, Irving H; Schultz, Harold D

    2015-07-15

    In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF. Copyright © 2015 the American Physiological Society.

  17. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

    Science.gov (United States)

    Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

    2015-04-15

    Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

  18. A Moment of Mindfulness: Computer-Mediated Mindfulness Practice Increases State Mindfulness.

    Directory of Open Access Journals (Sweden)

    Lynsey Mahmood

    Full Text Available Three studies investigated the use of a 5-minute, computer-mediated mindfulness practice in increasing levels of state mindfulness. In Study 1, 54 high school students completed the computer-mediated mindfulness practice in a lab setting and Toronto Mindfulness Scale (TMS scores were measured before and after the practice. In Study 2 (N = 90 and Study 3 (N = 61, the mindfulness practice was tested with an entirely online sample to test the delivery of the 5-minute mindfulness practice via the internet. In Study 2 and 3, we found a significant increase in TMS scores in the mindful condition, but not in the control condition. These findings highlight the impact of a brief, mindfulness practice for single-session, computer-mediated use to increase mindfulness as a state.

  19. Membrane fusion inducers, chloroquine and spermidine increase lipoplex-mediated gene transfection

    International Nuclear Information System (INIS)

    Wong-Baeza, Carlos; Bustos, Israel; Serna, Manuel; Tescucano, Alonso; Alcantara-Farfan, Veronica; Ibanez, Miguel; Montanez, Cecilia; Wong, Carlos; Baeza, Isabel

    2010-01-01

    Gene transfection into mammalian cells can be achieved with viral and non-viral vectors. Non-viral vectors, such as cationic lipids that form lipoplexes with DNA, are safer and more stable than viral vectors, but their transfection efficiencies are lower. Here we describe that the simultaneous treatment with a membrane fusion inducer (chlorpromazine or procainamide) plus the lysosomotropic agent chloroquine increases lipoplex-mediated gene transfection in human (HEK293 and C-33 A) and rat (PC12) cell lines (up to 9.2-fold), as well as in situ in BALB/c mice spleens and livers (up to 6-fold); and that the polyamine spermidine increases lipoplex-mediated gene transfection and expression in cell cultures. The use of these four drugs provides a novel, safe and relatively inexpensive way to considerably increase lipoplex-mediated gene transfection efficiency.

  20. Pollen-mediated gene flow in flax (Linum usitatissimum L.): can genetically engineered and organic flax coexist?

    Science.gov (United States)

    Jhala, A J; Bhatt, H; Topinka, K; Hall, L M

    2011-04-01

    Coexistence allows growers and consumers the choice of producing or purchasing conventional or organic crops with known standards for adventitious presence of genetically engineered (GE) seed. Flax (Linum usitatissimum L.) is multipurpose oilseed crop in which product diversity and utility could be enhanced for industrial, nutraceutical and pharmaceutical markets through genetic engineering. If GE flax were released commercially, pollen-mediated gene flow will determine in part whether GE flax could coexist without compromising other markets. As a part of pre-commercialization risk assessment, we quantified pollen-mediated gene flow between two cultivars of flax. Field experiments were conducted at four locations during 2006 and 2007 in western Canada using a concentric donor (20 × 20 m) receptor (120 × 120 m) design. Gene flow was detected through the xenia effect of dominant alleles of high α-linolenic acid (ALA; 18:3(cisΔ9,12,15)) to the low ALA trait. Seeds were harvested from the pollen recipient plots up to a distance of 50 m in eight directions from the pollen donor. High ALA seeds were identified using a thiobarbituric acid test and served as a marker for gene flow. Binomial distribution and power analysis were used to predict the minimum number of seeds statistically required to detect the frequency of gene flow at specific α (confidence interval) and power (1-β) values. As a result of the low frequency of gene flow, approximately 4 million seeds were screened to derive accurate quantification. Frequency of gene flow was highest near the source: averaging 0.0185 at 0.1 m but declined rapidly with distance, 0.0013 and 0.00003 at 3 and 35 m, respectively. Gene flow was reduced to 50% (O₅₀) and 90% (O₉₀) between 0.85 to 2.64 m, and 5.68 to 17.56 m, respectively. No gene flow was detected at any site or year > 35 m distance from the pollen source, suggesting that frequency of gene flow was ≤ 0.00003 (P = 0.95). Although it is not possible to

  1. Glycine facilitates gamma-glutamylcysteinylethyl ester-mediated increase in liver glutathione level.

    Science.gov (United States)

    Nishida, K; Ohta, Y; Ishiguro, I

    1997-08-27

    gamma-Glutamylcysteinylethyl ester (gamma-GCE) increases reduced glutathione (GSH) levels in GSH-depleted rat hepatocytes. Because glycine, a constituent of GSH, exists at 0.3 to 0.4 mM in rat plasma, we examined the influence of glycine added to the medium on the action of gamma-GCE to increase GSH levels in the rat hepatocytes. Glycine (0.2-0.8 mM) dose-dependently enhanced gamma-GCE-mediated increase in intracellular GSH levels with an increase in intracellular gamma-GCE levels. These results indicate that exogenous glycine facilitates gamma-GCE-mediated increase in intracellular GSH levels in rat hepatocytes possibly by enhancing the uptake of gamma-GCE into the cells.

  2. Increased flow sensitivity from gradient recalled echoes and short TRs

    International Nuclear Information System (INIS)

    Hearshen, D.O.; Froelich, J.W.; Wehrli, F.W.; Haggar, A.M.; Shimakawa, A.

    1986-01-01

    Time-of-flight effects from flow have been characterized in spin-echo images. ''Paradoxical'' enhancement and flow void are observed. Similar enhancement is seen on GRASS images. With no flow void and gradients existing throughout the volume, spins experiencing radio-frequency pulses will give rise to signals even for fast flow, providing a greater velocity sensitivity. GRASS images were obtained from a volunteer with a blood pressure cuff placed over the right thigh. With the cuff inflated, flow in the popliteal vein results in signal saturation. Increasing TR increases intensity in the popliteal vein relative to other vessels. This suggests a clinical role for the technique in assessment of slow flow

  3. Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats.

    Science.gov (United States)

    Li, Jing; He, Jiaojun; Du, Yuanhao; Cui, Jingjun; Ma, Ying; Zhang, Xuezhu

    2014-11-11

    To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.

  4. Air-mediated pollen flow from genetically modified to conventional crops.

    Science.gov (United States)

    Kuparinen, Anna; Schurr, Frank; Tackenberg, Oliver; O'Hara, Robert B

    2007-03-01

    Tools for estimating pollen dispersal and the resulting gene flow are necessary to assess the risk of gene flow from genetically modified (GM) to conventional fields, and to quantify the effectiveness of measures that may prevent such gene flow. A mechanistic simulation model is presented and used to simulate pollen dispersal by wind in different agricultural scenarios over realistic pollination periods. The relative importance of landscape-related variables such as isolation distance, topography, spatial configuration of the fields, GM field size and barrier, and environmental variation are examined in order to find ways to minimize gene flow and to detect possible risk factors. The simulations demonstrated a large variation in pollen dispersal and in the predicted amount of contamination between different pollination periods. This was largely due to variation in vertical wind. As this variation in wind conditions is difficult to control through management measures, it should be carefully considered when estimating the risk of gene flow from GM crops. On average, the predicted level of gene flow decreased with increasing isolation distance and with increasing depth of the conventional field, and increased with increasing GM field size. Therefore, at a national scale and over the long term these landscape properties should be accounted for when setting regulations for controlling gene flow. However, at the level of an individual field the level of gene flow may be dominated by uncontrollable variation. Due to the sensitivity of pollen dispersal to the wind, we conclude that gene flow cannot be summarized only by the mean contamination; information about the frequency of extreme events should also be considered. The modeling approach described in this paper offers a way to predict and compare pollen dispersal and gene flow in varying environmental conditions, and to assess the effectiveness of different management measures.

  5. Heparan sulfate proteoglycans mediate interstitial flow mechanotransduction regulating MMP-13 expression and cell motility via FAK-ERK in 3D collagen.

    Directory of Open Access Journals (Sweden)

    Zhong-Dong Shi

    2011-01-01

    Full Text Available Interstitial flow directly affects cells that reside in tissues and regulates tissue physiology and pathology by modulating important cellular processes including proliferation, differentiation, and migration. However, the structures that cells utilize to sense interstitial flow in a 3-dimensional (3D environment have not yet been elucidated. Previously, we have shown that interstitial flow upregulates matrix metalloproteinase (MMP expression in rat vascular smooth muscle cells (SMCs and fibroblasts/myofibroblasts via activation of an ERK1/2-c-Jun pathway, which in turn promotes cell migration in collagen. Herein, we focused on uncovering the flow-induced mechanotransduction mechanism in 3D.Cleavage of rat vascular SMC surface glycocalyx heparan sulfate (HS chains from proteoglycan (PG core proteins by heparinase or disruption of HS biosynthesis by silencing N-deacetylase/N-sulfotransferase 1 (NDST1 suppressed interstitial flow-induced ERK1/2 activation, interstitial collagenase (MMP-13 expression, and SMC motility in 3D collagen. Inhibition or knockdown of focal adhesion kinase (FAK also attenuated or blocked flow-induced ERK1/2 activation, MMP-13 expression, and cell motility. Interstitial flow induced FAK phosphorylation at Tyr925, and this activation was blocked when heparan sulfate proteoglycans (HSPGs were disrupted. These data suggest that HSPGs mediate interstitial flow-induced mechanotransduction through FAK-ERK. In addition, we show that integrins are crucial for mechanotransduction through HSPGs as they mediate cell spreading and maintain cytoskeletal rigidity.We propose a conceptual mechanotransduction model wherein cell surface glycocalyx HSPGs, in the presence of integrin-mediated cell-matrix adhesions and cytoskeleton organization, sense interstitial flow and activate the FAK-ERK signaling axis, leading to upregulation of MMP expression and cell motility in 3D. This is the first study to describe a flow-induced mechanotransduction

  6. The impact of menstrual phase on brachial artery flow-mediated dilatation during handgrip exercise in healthy premenopausal women.

    Science.gov (United States)

    D'Urzo, Katrina A; King, Trevor J; Williams, Jennifer S; Silvester, Morgan D; Pyke, Kyra E

    2018-02-01

    What is the central question of this study? The aim of this study was to determine the influence of menstrual phase on flow-mediated dilatation in response to sustained, exercise-induced increases in shear stress. What is the main finding and its importance? We showed, for the first time, that in healthy, premenopausal women the flow-mediated dilatation stimulated by exercise-induced increases in shear stress did not fluctuate across two phases of the menstrual cycle, despite significant fluctuations in oestrogen. This suggests that endothelial function is not consistently augmented in the high-oestrogen phase. Flow-mediated dilatation (FMD) in response to a sustained shear-stress stimulus (e.g. via handgrip exercise; HGEX) is emerging as a useful tool for assessing endothelial function; however, the impact of menstrual phase on HGEX-FMD is unknown. The purpose of this study was to determine whether HGEX-FMD fluctuates with cyclical changes in oestrogen concentrations over two discrete phases (low and high oestrogen) of the menstrual cycle. Brachial artery (BA) diameter and blood velocity were assessed with two-dimesional and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Participants (12 healthy, regularly cycling women, 21 ± 2 years of age) completed two experimental visits: (i) low oestrogen (early follicular, EF); and (ii) high oestrogen (late follicular, LF). Reactive hyperaemia-stimulated FMD (RH-FMD) and HGEX-FMD (6 min of handgrip exercise) were assessed during each visit. Results are mean values ± SD. Oestrogen increased from the EF to LF phase (EF, 33 ± 9 pg ml -1 ; LF, 161 ± 113 pg ml -1 , P = 0.003). However, neither the SR stimuli (HGEX, P = 0.501; RH, P = 0.173) nor the FMD responses differed between phases (EF versus LF: HGEX-FMD, 4.8 ± 2.8 versus 4.6 ± 2.2%, P = 0.601; RH-FMD, 7.9 ± 4.3 versus 6.4 ± 3.1%, P = 0.071). These results extend

  7. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

    Directory of Open Access Journals (Sweden)

    Davide Grassi

    2016-11-01

    Full Text Available (1 Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD before and after an oral fat in hypertensives; (2 Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3 Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006 and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001. Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001. Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001; (4 Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

  8. NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

    International Nuclear Information System (INIS)

    Li, Ruizhao; Zhang, Li; Shi, Wei; Zhang, Bin; Liang, Xinling; Liu, Shuangxin; Wang, Wenjian

    2013-01-01

    Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca 2+ was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca 2+ ]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway, which may

  9. NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruizhao, E-mail: liruizhao1979@126.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Li, E-mail: Zhanglichangde@163.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Southern Medical University, Guangzhou, Guangdong (China); Shi, Wei, E-mail: shiwei.gd@139.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Bin, E-mail: zhangbinyes@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liang, Xinling, E-mail: xinlingliang@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liu, Shuangxin, E-mail: mplsxi@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Wang, Wenjian, E-mail: wwjph@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China)

    2013-04-15

    Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway

  10. Pollen-mediated gene flow and seed exchange in small-scale Zambian maize farming, implications for biosafety assessment.

    Science.gov (United States)

    Bøhn, Thomas; Aheto, Denis W; Mwangala, Felix S; Fischer, Klara; Bones, Inger Louise; Simoloka, Christopher; Mbeule, Ireen; Schmidt, Gunther; Breckling, Broder

    2016-10-03

    Gene flow in agricultural crops is important for risk assessment of genetically modified (GM) crops, particularly in countries with a large informal agricultural sector of subsistence cultivation. We present a pollen flow model for maize (Zea mays), a major staple crop in Africa. We use spatial properties of fields (size, position) in three small-scale maize farming communities in Zambia and estimate rates of cross-fertilisation between fields sown with different maize varieties (e.g. conventional and transgene). As an additional factor contributing to gene flow, we present data on seed saving and sharing among farmers that live in the same communities. Our results show that: i) maize fields were small and located in immediate vicinity of neighboring fields; ii) a majority of farmers saved and shared seed; iii) modeled rates of pollen-mediated gene flow showed extensive mixing of germplasm between fields and farms and iv) as a result, segregation of GM and non-GM varieties is not likely to be an option in these systems. We conclude that the overall genetic composition of maize, in this and similar agricultural contexts, will be strongly influenced both by self-organised ecological factors (pollen flow), and by socially mediated intervention (seed recycling and sharing).

  11. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

    Science.gov (United States)

    Grassi, Davide; Draijer, Richard; Schalkwijk, Casper; Desideri, Giovambattista; D’Angeli, Anatolia; Francavilla, Sandro; Mulder, Theo; Ferri, Claudio

    2016-01-01

    (1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest. PMID:27854314

  12. Spatial and temporal assessment of pollen- and seed-mediated gene flow from genetically engineered plum Prunus domestica.

    Directory of Open Access Journals (Sweden)

    Ralph Scorza

    Full Text Available Pollen flow from a 0.46 ha plot of genetically engineered (GE Prunus domestica located in West Virginia, USA was evaluated from 2000-2010. Sentinel plum trees were planted at distances ranging from 132 to 854 m from the center of the GE orchard. Plots of mixed plum varieties and seedlings were located at 384, 484 and 998 m from the GE plot. Bee hives (Apis mellifera were dispersed between the GE plum plot and the pollen flow monitoring sites. Pollen-mediated gene flow from out of the GE plum plot to non-GE plums under the study conditions was low, only occurring at all in 4 of 11 years and then in only 0.31% of the 12,116 seeds analyzed. When it occurred, gene flow, calculated as the number of GUS positive embryos/total embryos sampled, ranged from 0.215% at 132 m from the center of the GE plum plot (28 m from the nearest GE plum tree to 0.033-0.017% at longer distances (384-998 m. Based on the percentage of GUS positive seeds per individual sampled tree the range was 0.4% to 12%. Within the GE field plot, gene flow ranged from 4.9 to 39%. Gene flow was related to distance and environmental conditions. A single year sample from a sentinel plot 132 m from the center of the GE plot accounted for 65% of the total 11-year gene flow. Spatial modeling indicated that gene flow dramatically decreased at distances over 400 m from the GE plot. Air temperature and rainfall were, respectively, positively and negatively correlated with gene flow, reflecting the effects of weather conditions on insect pollinator activity. Seed-mediated gene flow was not detected. These results support the feasibility of coexistence of GE and non-GE plum orchards.

  13. Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.

    Science.gov (United States)

    Dreiling, Michelle; Bischoff, Sabine; Schiffner, Rene; Rupprecht, Sven; Kiehntopf, Michael; Schubert, Harald; Witte, Otto W; Nathanielsz, Peter W; Schwab, Matthias; Rakers, Florian

    2016-09-01

    Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

  14. Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.

    Science.gov (United States)

    Belcik, J Todd; Mott, Brian H; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J; Ammi, Azzdine; Linden, Joel M; Lindner, Jonathan R

    2015-04-01

    Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (Pultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; Pultrasound and microbubbles by 70% (Pultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase. © 2015 American Heart Association, Inc.

  15. Combined modeling of cell aggregation and adhesion mediated by receptor–ligand interactions under shear flow

    Directory of Open Access Journals (Sweden)

    Yu Du

    2015-11-01

    Full Text Available Blood cell aggregation and adhesion to endothelial cells under shear flow are crucial to many biological processes such as thrombi formation, inflammatory cascade, and tumor metastasis, in which these cellular interactions are mainly mediated by the underlying receptor–ligand bindings. While theoretical modeling of aggregation dynamics and adhesion kinetics of interacting cells have been well studied separately, how to couple these two processes remains unclear. Here we develop a combined model that couples cellular aggregation dynamics and adhesion kinetics under shear flow. The impacts of shear rate (or shear stress and molecular binding affinity were elucidated. This study provides a unified model where the action of a fluid flow drives cell aggregation and adhesion under the modulations of the mechanical shear flow and receptor–ligand interaction kinetics. It offers an insight into understanding the relevant biological processes and functions.

  16. New heavy crude oil flow improver increases delivery : application scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Pierce, J.; Johnston, R.; Lauzon, P. [ConocoPhillips Specialty Products Inc., Houston, TX (United States)

    2009-07-01

    Flow improvers or drag reducing agents have been used for over 25 years as a method to increase fluid flow in hydrocarbon pipelines. The technology is effective in refined projects, light and medium crude oils. This paper presented a new development in flow improver technology that allows treatment of heavy crude oil slates. It discussed case studies of flow improver treatment of heavy oils in various pipeline system as well as factors that affect commercial success. tabs., figs.

  17. A Moment of Mindfulness: Computer-Mediated Mindfulness Practice Increases State Mindfulness

    OpenAIRE

    Mahmood, L.; Hopthrow, T.; Randsley de Moura, G.

    2016-01-01

    Three studies investigated the use of a 5-minute, computer-mediated mindfulness practice in increasing levels of state mindfulness. In Study 1, 54 high school students completed the computer-mediated mindfulness practice in a lab setting and Toronto Mindfulness Scale (TMS) scores were measured before and after the practice. In Study 2 (N = 90) and Study 3 (N = 61), the mindfulness practice was tested with an entirely online sample to test the delivery of the 5-minute mindfulness practice via ...

  18. Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation.

    Directory of Open Access Journals (Sweden)

    Kyung Min Kim

    Full Text Available Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif, a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.

  19. Trans monounsaturated fatty acids and saturated fatty acids have similar effects on postprandial flow-mediated vasodilation

    NARCIS (Netherlands)

    Roos, de N.M.; Siebelink, E.; Bots, M.L.; Tol, van A.; Schouten, E.G.; Katan, M.B.

    2002-01-01

    Objective: Several studies suggest that a fatty meal impairs flow-mediated vasodilation (FMD), a measur9e of endothelial function. We tested whether the impairment was greater for trans fats than for saturated fats. We did this because we previously showed that replacement of saturated fats by trans

  20. Moderated mediation to identify the knowledge stocks, learning flows and barriers at a Dutch telecom operator

    NARCIS (Netherlands)

    de Schryver, Tom; Rosendaal, Bas

    2013-01-01

    Drawing on the 4I-model of Crossan et al. (1999), we have identified the knowledge stocks, learning flows and barriers at a Dutch telecom operator by means of moderated mediation. In this company, the strategic relevant knowledge stocks move in the same direction and many processes support their

  1. Service Interaction Flow Analysis Technique for Service Personalization

    DEFF Research Database (Denmark)

    Korhonen, Olli; Kinnula, Marianne; Syrjanen, Anna-Liisa

    2017-01-01

    Service interaction flows are difficult to capture, analyze, outline, and represent for research and design purposes. We examine how variation of personalized service flows in technology-mediated service interaction can be modeled and analyzed to provide information on how service personalization...... could support interaction. We have analyzed service interaction cases in a context of technology-mediated car rental service. With the analysis technique we propose, inspired by Interaction Analysis method, we were able to capture and model the situational service interaction. Our contribution regarding...... technology-mediated service interaction design is twofold: First, with the increased understanding on the role of personalization in managing variation in technology-mediated service interaction, our study contributes to designing service management information systems and human-computer interfaces...

  2. Dopexamine increases internal mammary artery blood flow following coronary artery bypass grafting.

    LENUS (Irish Health Repository)

    Flynn, Michael J

    2012-02-03

    OBJECTIVE: Vasoactive agents and inotropes influence conduit-coronary blood flow following coronary artery bypass grafting (CABG). It was hypothesized that dopexamine hydrochloride, a dopamine A-1 (DA-1) and beta(2) agonist would increase conduit-coronary blood flow. A prospective randomized double blind clinical trial was carried out to test this hypothesis. DA-1 receptors have previously been localized to human left ventricle. METHODS: Twenty-six American Society of Anaesthesiology class 2-3 elective coronary artery bypass graft patients who did not require inotropic support on separation from cardiopulmonary bypass (CPB) were studied. According to a randomized allocation patients received either dopexamine (1 microg\\/kg per min) or placebo (saline) by intravenous infusion for 15 min. Immediately prior to and at 5,10 and 15 min of infusion, blood flow through the internal mammary and vein grafts (Transit time flow probes, Transonic Ltd.), heart rate, cardiac index, mean arterial pressure and pulmonary haemodynamics were noted. The data were analysed using multivariate analysis of variance. RESULTS: Low-dose dopexamine (1 microg\\/kg per min) caused a significant increase in mammary graft blood flow compared to placebo at 15 min of infusion (P=0.028, dopexamine group left internal mammary artery (LIMA) flow of 43.3+\\/-14.2 ml\\/min, placebo group LIMA flow at 26.1+\\/-16.3 ml\\/min). Dopexamine recipients demonstrated a non-significant trend to increased saphenous vein graft flow (P=0.059). Increased heart rate was the only haemodynamic change induced by dopexamine (P=0.004, dopexamine group at 85.2+\\/-9.6 beats\\/min and placebo group at 71.1+\\/-7.6 beats\\/min after 15 min of infusion). CONCLUSION: This study demonstrates that administration of dopexamine (1 microg\\/kg per min) was associated with a significant increase in internal mammary artery graft blood flow with mild increase in heart rate being the only haemodynamic change. Low-dose dopexamine may

  3. Nitroglycerin-mediated, but not flow-mediated vasodilation, is associated with blunted nocturnal blood pressure fall in patients with resistant hypertension.

    Science.gov (United States)

    Fontes-Guerra, Priscila C A; Cardoso, Claudia R L; Muxfeldt, Elizabeth S; Salles, Gil F

    2015-08-01

    Endothelial function by flow-mediated (FMD) and nitroglycerin-mediated vasodilations (NMD) was scarcely investigated in resistant hypertension. We aimed to assess the independent correlates of FMD and NMD in resistant hypertensive patients, particularly their associations with ambulatory blood pressures (BP) and nocturnal BP fall patterns. In a cross-sectional study, 280 resistant hypertensive patients performed 24-h ambulatory BP monitoring, carotid-femoral pulse wave velocity, polysomnography, and brachial artery FMD and NMD by high-resolution ultrasonography. Independent correlates of FMD, NMD, and brachial artery diameter (BAD) were assessed by multiple linear and logistic regressions. Median (interquartile range) FMD was 0.75% (-0.6 to +4.4%) and NMD was 11.8% (7.1-18.4%). Baseline BAD and diabetes were independently associated with both FMD and NMD. Older age and prior cardiovascular diseases were associated with altered FMD, whereas higher night-time SBP and lower nocturnal SBP fall were associated with impaired NMD. Moreover, there was a significant gradient of impaired NMD according to blunted nocturnal BP decline patterns. BAD was independently associated with age, sex, BMI, albuminuria, and nocturnal SBP fall. Further adjustments to blood flow velocity, aortic stiffness, plasma aldosterone concentration, and sleep apnea did not change these relationships. NMD, but not FMD, is independently associated with unfavorable night-time BP levels and nondipping patterns, and may be a better cardiovascular risk marker in patients with resistant hypertension. BAD also may provide additional prognostic information.

  4. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Schreuder, T.H.A.; Lotringen, J.H. van; Hopman, M.T.E.; Thijssen, D.H.J.

    2014-01-01

    Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact

  5. High bias gas flows increase lung injury in the ventilated preterm lamb.

    Directory of Open Access Journals (Sweden)

    Katinka P Bach

    Full Text Available BACKGROUND: Mechanical ventilation of preterm babies increases survival but can also cause ventilator-induced lung injury (VILI, leading to the development of bronchopulmonary dysplasia (BPD. It is not known whether shear stress injury from gases flowing into the preterm lung during ventilation contributes to VILI. METHODS: Preterm lambs of 131 days' gestation (term = 147 d were ventilated for 2 hours with a bias gas flow of 8 L/min (n = 13, 18 L/min (n = 12 or 28 L/min (n = 14. Physiological parameters were measured continuously and lung injury was assessed by measuring mRNA expression of early injury response genes and by histological analysis. Control lung tissue was collected from unventilated age-matched fetuses. Data were analysed by ANOVA with a Tukey post-hoc test when appropriate. RESULTS: High bias gas flows resulted in higher ventilator pressures, shorter inflation times and decreased ventilator efficiency. The rate of rise of inspiratory gas flow was greatest, and pulmonary mRNA levels of the injury markers, EGR1 and CTGF, were highest in lambs ventilated with bias gas flows of 18 L/min. High bias gas flows resulted in increased cellular proliferation and abnormal deposition of elastin, collagen and myofibroblasts in the lung. CONCLUSIONS: High ventilator bias gas flows resulted in increased lung injury, with up-regulation of acute early response genes and increased histological lung injury. Bias gas flows may, therefore, contribute to VILI and BPD.

  6. Hyperdynamic sepsis modifies a PEEP-mediated redistribution in organ blood flows

    International Nuclear Information System (INIS)

    Bersten, A.D.; Gnidec, A.A.; Rutledge, F.S.; Sibbald, W.J.

    1990-01-01

    Changes in organ blood flow (Q) produced by 20 cm H2O positive end-expiratory pressure (PEEP) were measured before and after the induction of hyperdynamic sepsis in nine unanesthetized sheep. During the baseline nonseptic study, PEEP was associated with a 9% fall in thermodilution-measured systemic Q, although arterial perfusing pressures were unaffected. Concurrently, microsphere-derived Q was maintained to the brain and heart, but fell to liver, spleen, pancreas, kidney, large intestine, and gastrocnemius. Twenty-four to 36 h after cecal ligation and perforation, a pre-PEEP septic study demonstrated an increase in all of the cardiac index (CI) and systemic O2 delivery when compared with the nonseptic study, whereas whole-body O2 extraction was depressed. Although PEEP depressed systemic Q during the septic study to a greater extent than during the nonseptic study (p less than 0.02), absolute organ Q fell only to pancreas, liver, and spleen. Relative to the simultaneous fall in the CI, Q to some splanchnic organs was not depressed by PEEP to the same magnitude in the septic as in the nonseptic study. When an infusion of Ringer's lactate subsequently restored systemic Q to pre-PEEP septic levels, individual flows that had been depressed by PEEP were not restored. Furthermore, Q-kidney continued to fall, such that the postfluid Q-kidney (-19%) was significantly less than was demonstrated in the pre-PEEP septic study. We postulate that differences noted in the distribution of organ Q between the nonseptic and hyperdynamic septic studies after the application of PEEP were secondary to the vasculopathy of sepsis and/or an alteration in the function of specific organ microcirculations. However, these data do not address whether the changes in organ Q distribution after a PEEP-mediated depression in systemic Q during sepsis significantly restricted tissue DO2

  7. Soluble intercellular adhesion molecule 1 and flow-mediated dilatation are related to the estimated risk of coronary heart disease independently from each other

    NARCIS (Netherlands)

    Witte, D.R.; Broekmans, W.M.R.; Kardinaal, A.F.M.; Klöpping-Ketelaars, I.A.A.; Poppel, G. van; Bots, M.L.; Kluft, C.; Princen, J.M.G.

    2003-01-01

    Background: Flow mediated dilatation (FMD) of the brachial artery and soluble intercellular adhesion molecule 1 (sICAM-1) are measures of distinct functions of the endothelium, reflecting nitric oxide (NO)-mediated and pro-inflammatory status, respectively. The comparative value of the two measures

  8. Data describing the flow-mediated vasodilation responses and blood pressure in young adult humans after a single dose of oral edible emu oil

    Directory of Open Access Journals (Sweden)

    Tadayoshi Miyashita

    2018-04-01

    Full Text Available The data provided herein include flow-mediated vasodilation responses, represented by changes in arterial diameter, and blood pressure in young adults after a single oral dose of edible emu oil or placebo (cross-over design. Ten healthy men and 10 healthy women participated. Increased blood flow in the antebrachial region was induced by inflating a pressure cuff and subsequently releasing the pressure by deflating the cuff. After the release, the arterial diameter was continuously monitored for 110 sec using ultrasonic diagnostic equipment. The changes in the arterial diameter from 20 to 110 sec post-cuff deflation are described in line graphs and tables. In addition, systolic and diastolic blood pressure data are provided in a table.

  9. Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow

    International Nuclear Information System (INIS)

    Semino, Carlos E.; Kamm, Roger D.; Lauffenburger, Douglas A.

    2006-01-01

    We show here that autocrine ligand activation of epidermal growth factor (EGF) receptor in combination with interstitial flow is critically involved in the morphogenetic response of endothelial cells to VEGF stimulation. Human umbilical vein endothelial cell (HUVEC) monolayers cultured on a collagen gel and exposed to low interstitial flow in the absence of EGF and VEGF remained viable and mitotic but exhibited little evidence of vascular morphogenesis. Addition of VEGF produced a flow-dependent morphogenetic response within 48 to 72 h, characterized by branched capillary-like structures. The response was substantially abolished by inhibitors related to the autocrine EGF receptor pathway including Galardin, AG1478, PD98059, and an EGF receptor-blocking antibody, indicating that regulation of the morphogenetic process operates via autocrine EGF receptor activation. Moreover, we observed that in our system the EGF receptor was always activated independently of the interstitial flow, and, in addition, the EGF receptor inhibitors used above reduced the phosphorylation state of the receptor, correlating with inhibition of capillary morphogenesis. Finally, 5'bromo-2'-deoxyuridine (BrdU) labeling identified dividing cells at the monolayer but not in the extending capillary-like structures. EGF pathway inhibitors Galardin and AG1478 did not reduce BrdU incorporation in the monolayer, indicating that the EGF-receptor-mediated morphogenetic behavior is mainly due to cell migration rather than proliferation. Based on these results, we propose a two-step model for in vitro capillary morphogenesis in response to VEGF stimulation with interstitial fluid flow: monolayer maintenance by mitotic activity independent of EGF receptors and a migratory response mediated by autocrine EGF receptor activation wherein cells establish capillary-like structures

  10. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  11. Combined Increases in Mitochondrial Cooperation and Oxygen Photoreduction Compensate for Deficiency in Cyclic Electron Flow in Chlamydomonas reinhardtii[W][OPEN

    Science.gov (United States)

    Dang, Kieu-Van; Plet, Julie; Tolleter, Dimitri; Jokel, Martina; Cuiné, Stéphan; Carrier, Patrick; Auroy, Pascaline; Richaud, Pierre; Johnson, Xenie; Alric, Jean; Allahverdiyeva, Yagut; Peltier, Gilles

    2014-01-01

    During oxygenic photosynthesis, metabolic reactions of CO2 fixation require more ATP than is supplied by the linear electron flow operating from photosystem II to photosystem I (PSI). Different mechanisms, such as cyclic electron flow (CEF) around PSI, have been proposed to participate in reequilibrating the ATP/NADPH balance. To determine the contribution of CEF to microalgal biomass productivity, here, we studied photosynthesis and growth performances of a knockout Chlamydomonas reinhardtii mutant (pgrl1) deficient in PROTON GRADIENT REGULATION LIKE1 (PGRL1)–mediated CEF. Steady state biomass productivity of the pgrl1 mutant, measured in photobioreactors operated as turbidostats, was similar to its wild-type progenitor under a wide range of illumination and CO2 concentrations. Several changes were observed in pgrl1, including higher sensitivity of photosynthesis to mitochondrial inhibitors, increased light-dependent O2 uptake, and increased amounts of flavodiiron (FLV) proteins. We conclude that a combination of mitochondrial cooperation and oxygen photoreduction downstream of PSI (Mehler reactions) supplies extra ATP for photosynthesis in the pgrl1 mutant, resulting in normal biomass productivity under steady state conditions. The lower biomass productivity observed in the pgrl1 mutant in fluctuating light is attributed to an inability of compensation mechanisms to respond to a rapid increase in ATP demand. PMID:24989042

  12. Neural control of adrenal medullary and cortical blood flow during hemorrhage

    International Nuclear Information System (INIS)

    Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

    1987-01-01

    Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with 153 Gd, 114 In, 113 Sn, 103 Ru, 95 Nb or 46 Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension

  13. Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA-451 redistribution in gastric cancer infiltrated T cells.

    Science.gov (United States)

    Liu, Feng; Bu, Zhouyan; Zhao, Feng; Xiao, Daping

    2018-01-01

    MicroRNA (miR)-451 is a cell metabolism-related miRNA that can mediate cell energy-consuming models by several targets. As miR-451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T-helper 17 (Th17) cells, we sought to investigate whether miR-451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting expression of miR-451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring the exosome-enveloped miR-451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR-451 decreased significantly in gastric cancer (GC) tissues but increased in infiltrated T cells and exosomes; tumor miR-451 was negatively related to infiltrated T cells and exosome miR-451. Exosome miR-451 can not only serve as an indicator for poor prognosis of post-operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR-451 can redistribute from cancer cells to T cells with low glucose treatment. Decreased 5' AMP-activated protein kinase (AMPK) and increased mTOR activity was investigated in miR-451 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR-451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR-451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis

    DEFF Research Database (Denmark)

    Wang, Qian; Paulson, O B; Lassen, N A

    1993-01-01

    by acetazolamide (Az), a drug that induces brain extracellular acidosis, which triggers its effect on CBF. We compared the results to the inhibitory effect of indomethacin on the CBF increase during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to block almost...... completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but it did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO2 reactivity by a nonprostaglandin-mediated mechanism that directly......Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral arterioles. We therefore investigated the effect of indomethacin on the CBF increase caused...

  15. Solute concentration affects bradykinin-mediated increases in renal prostaglandin E2

    International Nuclear Information System (INIS)

    Zenser, T.V.; Davis, E.S.; Rapp, N.S.; Davis, B.B.

    1981-01-01

    The effects of solute concentration on the bradykinin-mediated increase in inner medullary slice prostaglandin E2 (PGE2) synthesis were investigated. PG content was determined by specific RIA. Bradykinin stimulation was prevented by the addition of the following solutes to Krebs buffer: 1.0 M urea, 0.5 or 1.0 M NaCl, 0.5 or 1.0 M mannitol, 1.0 M urea plus 0.5 M NaCl, or 1.0 M mannitol plus 0.5 M NaCl. By contrast, basal PGE2 synthesis was increased by 1.0 M mannitol or by 1.0 M mannitol plus 0.5 M NaCl, but decreased by 1.0 M urea. Urea elicited a concentration-dependent, reversible inhibition of bradykinin stimulation, with 0.01 M urea being the lowest effective concentration. By contrast, basal PGE2 synthesis was only reduced at a urea concentration greater than 0.6 M. Arachidonic acid-mediated increases in both PGE2 and PGF2 alpha synthesis were not prevented by 1.0 M urea. The latter suggests that neither PG endoperoxide synthetase nor PG endoperoxide E isomerase are inhibited by urea. The data indicate that different hypertonic solutions have different effects on basal PG production, but all inhibit bradykinin stimulation

  16. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

    Science.gov (United States)

    Schreuder, Tim H A; van Lotringen, Jaap H; Hopman, Maria T E; Thijssen, Dick H J

    2014-09-01

    Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact of endothelin receptor blockade (bosentan) on exercise-induced blood flow in the brachial artery and on pre- and postexercise endothelial function in type 2 diabetes patients (n = 9, 60 ± 7 years old) and control subjects (n = 10, 60 ± 5 years old). Subjects reported twice to the laboratory to perform hand-grip exercise in the presence of endothelin receptor blockade or placebo. We examined brachial artery endothelial function (via flow-mediated dilatation) before and after exercise, as well as blood flow during exercise. Endothelin receptor blockade resulted in a larger increase in blood flow during exercise in type 2 diabetes patients (P = 0.046), but not in control subjects (P = 0.309). Exercise increased shear rate across the exercise protocol, unaffected by endothelin receptor blockade. Exercise did not alter brachial artery diameter in either group, but endothelin receptor blockade resulted in a larger brachial artery diameter in type 2 diabetes patients (P = 0.033). Exercise significantly increased brachial artery flow-mediated dilatation in both groups, unaffected by endothelin receptor blockade. Endothelin receptor blockade increased exercise-induced brachial artery blood flow in type 2 diabetes patients, but not in control subjects. Despite this effect of endothelin receptor blockade on blood flow, we found no impact on baseline or post-exercise endothelial function in type 2 diabetes patients or control subjects, possibly related to normalization of the shear stimulus during exercise. The successful increase in blood flow during exercise in type 2 diabetes patients through endothelin receptor blockade may have beneficial effects in

  17. Flow Patterns in an Open Channel Confluence with Increasingly Dominant Tributary Inflow

    Directory of Open Access Journals (Sweden)

    Laurent Schindfessel

    2015-08-01

    Full Text Available Despite the ratio of incoming discharges being recognized as a key parameter in open-channel confluence hydrodynamics, little is known about the flow patterns when the tributary provides more than 90% of the total discharge. This paper offers a systematic study of flow features when the tributary becomes increasingly dominant in a 90° confluence with a fixed concordant bed. Large-eddy simulations are used to investigate the three-dimensional complex flow patterns for three different discharge ratios. It is found that the tributary flow impinges on the opposing bank when the tributary flow becomes sufficiently dominant, causing a recirculating eddy in the upstream channel of the confluence, which induces significant changes in the incoming velocity distribution. Moreover, it results in stronger helicoidal cells in the downstream channel, along with zones of upwelling flow. In turn, the changed flow patterns also influence the mixing layer and the flow recovery. Finally, intermittent events of stronger upwelling flow are discerned. Improved understanding of flow patterns at confluences where the tributary is dominant is applicable to both engineering and earth sciences.

  18. Thoracoabdominal mobility evaluation by photogrammetry in newborns after expiratory flow increase technique

    Directory of Open Access Journals (Sweden)

    Júlia Isabel de Araújo Guerra

    Full Text Available Abstract Introduction: Expiratory flow increase is a maneuver of respiratory physical therapy that promotes flow direction to the upper airways however, when applied in newborns, it may result in changes of thoracoabdominal mobility. Objective: To evaluate the thoracoabdominal mobility by photogrammetry in newborns after expiratory flow increase technique. Methods: Experimental blind study performed with newborns in supine position on a support table with upper limbs flexed, abducted and externally rotated and hip flexed at 110°. Adhesive markers were allocated for geometric delimitation of the thoracoabdominal compartment and expiratory flow increase technique was performed for 5 minutes with the therapist’s hands on the thorax and abdomen. Newborns were filmed before and after the maneuver and the frames were analyzed in AutoCAD® software by a blinded investigator at the time of the procedure. The largest and the smallest thoracoabdominal area were expressed in cm2 and the mean values were compared between two moments (pre and post maneuver by paired t test. Results: Twenty newborns with a mean age of 39 weeks were included. Before the maneuver, thoracoabdominal area was 56.1 cm2 during expiration and 59.7 cm2 during inspiration, and after the maneuver the value was 56.2 cm2 during expiration and 59.8 cm2 during inspiration, with no statistical difference between before and after (p = 0.97, p = 0.92, respectively. Conclusion: Results demonstrate that expiratory flow increase technique does not seem to change thoracoabdominal mobility of healthy newborns.

  19. Redundant Vasodilator Pathways Underlying Radial Artery Flow-Mediated Dilation Are Preserved in Healthy Aging

    Directory of Open Access Journals (Sweden)

    Kevin D. Ballard

    2014-01-01

    Full Text Available Background. Blocking nitric oxide (NO and vasodilator prostanoids (PN does not consistently reduce flow-mediated dilation (FMD in young adults. The impact of aging on the contribution of NO and PG to FMD is unknown. Methods. FMD was measured in older adults (n=10, 65±3 y after arterial infusion of saline, N(G-monomethyl-L-arginine (L-NMMA, and ketorolac + L-NMMA. Data were compared to published data in young adults. Results. L-NMMA reduced FMD in older adults (8.9±3.6 to 5.9±3.7% although this was not statistically significant (P=0.08 and did not differ (P=0.74 from the reduction observed in young adults (10.0±3.8 to 7.6±4.7%; P=0.03. Blocking PN did not affect FMD in young or older adults. In older adults, L-NMMA reduced (n=6; range = 36–123% decrease, augmented (n=3; 10–122% increase, or did not change FMD (n=1; 0.4% increase. After PN blockade, FMD responses were reduced (n=2, augmented (n=6, or unaffected (n=1. Conclusions. NO or PN blockade did not consistently reduce FMD in healthy older adults, suggesting the existence of redundant vasodilator phenotypes as observed previously in young adults.

  20. Secondary flow in turbulent ducts with increasing aspect ratio

    Science.gov (United States)

    Vinuesa, R.; Schlatter, P.; Nagib, H. M.

    2018-05-01

    Direct numerical simulations of turbulent duct flows with aspect ratios 1, 3, 5, 7, 10, and 14.4 at a center-plane friction Reynolds number Reτ,c≃180 , and aspect ratios 1 and 3 at Reτ,c≃360 , were carried out with the spectral-element code nek5000. The aim of these simulations is to gain insight into the kinematics and dynamics of Prandtl's secondary flow of the second kind and its impact on the flow physics of wall-bounded turbulence. The secondary flow is characterized in terms of the cross-plane component of the mean kinetic energy, and its variation in the spanwise direction of the flow. Our results show that averaging times of around 3000 convective time units (based on duct half-height h ) are required to reach a converged state of the secondary flow, which extends up to a spanwise distance of around ≃5 h measured from the side walls. We also show that if the duct is not wide enough to accommodate the whole extent of the secondary flow, then its structure is modified as reflected through a different spanwise distribution of energy. Another confirmation of the extent of the secondary flow is the decay rate of kinetic energy of any remnant secondary motions for zc/h >5 (where zc is the spanwise distance from the corner) in aspect ratios 7, 10, and 14.4, which exhibits a decreasing level of energy with increasing averaging time ta, and in its rapid rate of decay given by ˜ta-1 . This is the same rate of decay observed in a spanwise-periodic channel simulation, which suggests that at the core, the kinetic energy of the secondary flow integrated over the cross-sectional area, , behaves as a random variable with zero mean, with rate of decay consistent with central limit theorem. Long-time averages of statistics in a region of rectangular ducts extending about the width of a well-designed channel simulation (i.e., extending about ≃3 h on each side of the center plane) indicate that ducts or experimental facilities with aspect ratios larger than 10 may

  1. Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

    International Nuclear Information System (INIS)

    Voss, Melanie J; Möller, Mischa F; Powe, Desmond G; Niggemann, Bernd; Zänker, Kurt S; Entschladen, Frank

    2011-01-01

    Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines. Migration was assessed in luminal (MCF-7), post-EMT (MDA-MB-231, MDA-MB-435S), and basal-like (MDA-MB-468) human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG) was tested. Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration. Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients

  2. A Point-of-Need infrared mediated PCR platform with compatible lateral flow strip for HPV detection.

    Science.gov (United States)

    Liu, Wenjia; Zhang, Mingfang; Liu, Xiaoyan; Sharma, Alok; Ding, Xianting

    2017-10-15

    With the increasing need of monitoring the epidemiology of serious infectious diseases, food hygiene, food additives and pesticide residues, it is urgent to develop portable, easy-to-use, inexpensive and rapid molecular diagnostic tools. Herein, we demonstrate a prototype of IR mediated Conducting Oil and CarbOn Nanotube circUlaTing PCR (IR-COCONUT PCR) platform for nucleic acid amplification. The presented platform offers a new solution for miniaturized PCR instruments with non-contact heaters by using conducting oil and carbon nanotube as a medium in IR mediated PCR. This novel platform offers accurate and flexible control of temperature through the integration of PID (proportional-integral-derivative) algorithms to manipulate the duty cycle of the voltage signals of IR LED and a peristaltic pump. The ramping rate of the introduced platform in current study is 1.5°C/s for heating speed and -2.0°C/s for cooling speed. This platform fulfills 30 thermal cycles within 50min which is a match to the conventional bench-top PCR thermo cyclers. For demonstration purpose, human papillomavirus (HPV) patient cervical swab specimens were examined. Downstream lateral flow strip (LFS) was also developed to quantity the PCR products from the IR-COCONUT PCR device within 25min. This PCR platform together with the compatible LFS shows great potential for in-field and Point-of-Need (PoN) testing of genetic or contagious diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Low crop plant population densities promote pollen-mediated gene flow in spring wheat (Triticum aestivum L.).

    Science.gov (United States)

    Willenborg, Christian J; Brûlé-Babel, Anita L; Van Acker, Rene C

    2009-12-01

    Transgenic wheat is currently being field tested with the intent of eventual commercialization. The development of wheat genotypes with novel traits has raised concerns regarding the presence of volunteer wheat populations and the role they may play in facilitating transgene movement. Here, we report the results of a field experiment that investigated the potential of spring wheat plant population density and crop height to minimize gene flow from a herbicide-resistant (HR) volunteer population to a non-HR crop. Pollen-mediated gene flow (PMGF) between the HR volunteer wheat population and four conventional spring wheat genotypes varying in height was assessed over a range of plant population densities. Natural hybridization events between the two cultivars were detected by phenotypically scoring plants in F(1) populations followed by verification with Mendelian segregation ratios in the F(1:2) families. PMGF was strongly associated with crop yield components, but showed no association with flowering synchrony. Maximum observed PMGF was always less than 0.6%, regardless of crop height and density. The frequency of PMGF in spring wheat decreased exponentially with increasing plant population density, but showed no dependence on either crop genotype or height. However, increasing plant densities beyond the recommended planting rate of 300 cropped wheat plants m(-2) provided no obvious benefit to reducing PMGF. Nevertheless, our results demonstrate a critical plant density of 175-200 cropped wheat plants m(-2) below which PMGF frequencies rise exponentially with decreasing plant density. These results will be useful in the development of mechanistic models and best management practices that collectively facilitate the coexistence of transgenic and nontransgenic wheat crops.

  4. Mechanisms of temporal variation in single-nephron blood flow in rats

    DEFF Research Database (Denmark)

    Yip, K P; Holstein-Rathlou, N H; Marsh, D J

    1993-01-01

    Modified laser-Doppler velocimetry was used to determine the number of different mechanisms regulating single-nephron blood flow. Two oscillations were identified in star vessel blood flow, one at 20-50 mHz and another at 100-200 mHz. Tubuloglomerular feedback (TGF) mediates the slower oscillation......, and the faster one is probably myogenic in origin. Acute hypertension increased autospectral power in the 20-50 mHz and 100-200 mHz frequency bands to 282 +/- 50 and 248 +/- 64%, respectively, of control even though mean single-nephron blood flow was autoregulated. Mean blood flow increased 24.6 +/- 6.1% when...... components in efferent arteriole blood flow....

  5. Feedback-Mediated Upper Extremities Exercise: Increasing Patient Motivation in Poststroke Rehabilitation

    Directory of Open Access Journals (Sweden)

    Maša D. Popović

    2014-01-01

    Full Text Available Purpose. This proof-of-concept study investigated whether feedback-mediated exercise (FME of the affected arm of hemiplegic patients increases patient motivation and promotes greater improvement of motor function, compared to no-feedback exercise (NFE. Method. We developed a feedback-mediated treatment that uses gaming scenarios and allows online and offline monitoring of both temporal and spatial characteristics of planar movements. Twenty poststroke hemiplegic inpatients, randomly assigned to the FME and NFE group, received therapy five days a week for three weeks. The outcome measures were evaluated from the following: (1 the modified drawing test (mDT, (2 received therapy time—RTT, and (3 intrinsic motivation inventory—IMI. Results. The FME group patients showed significantly higher improvement in the speed metric (P<0.01, and smoothness metric (P<0.01, as well as higher RTT (P<0.01. Significantly higher patient motivation is observed in the FME group (interest/enjoyment subscale (P<0.01 and perceived competence subscale (P<0.01. Conclusion. Prolonged endurance in training and greater improvement in certain areas of motor function, as well as very high patient motivation and strong positive impressions about the treatment, suggest the positive effects of feedback-mediated treatment and its high level of acceptance by patients.

  6. The effect of α1 -adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude.

    Science.gov (United States)

    Tymko, Michael M; Tremblay, Joshua C; Hansen, Alex B; Howe, Connor A; Willie, Chris K; Stembridge, Mike; Green, Daniel J; Hoiland, Ryan L; Subedi, Prajan; Anholm, James D; Ainslie, Philip N

    2017-03-01

    Our objective was to quantify endothelial function (via brachial artery flow-mediated dilatation) at sea level (344 m) and high altitude (3800 m) at rest and following both maximal exercise and 30 min of moderate-intensity cycling exercise with and without administration of an α 1 -adrenergic blockade. Brachial endothelial function did not differ between sea level and high altitude at rest, nor following maximal exercise. At sea level, endothelial function decreased following 30 min of moderate-intensity exercise, and this decrease was abolished with α 1 -adrenergic blockade. At high altitude, endothelial function did not decrease immediately after 30 min of moderate-intensity exercise, and administration of α 1 -adrenergic blockade resulted in an increase in flow-mediated dilatation. Our data indicate that post-exercise endothelial function is modified at high altitude (i.e. prolonged hypoxaemia). The current study helps to elucidate the physiological mechanisms associated with high-altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. We examined the hypotheses that (1) at rest, endothelial function would be impaired at high altitude compared to sea level, (2) endothelial function would be reduced to a greater extent at sea level compared to high altitude after maximal exercise, and (3) reductions in endothelial function following moderate-intensity exercise at both sea level and high altitude are mediated via an α 1 -adrenergic pathway. In a double-blinded, counterbalanced, randomized and placebo-controlled design, nine healthy participants performed a maximal-exercise test, and two 30 min sessions of semi-recumbent cycling exercise at 50% peak output following either placebo or α 1 -adrenergic blockade (prazosin; 0.05 mg kg  -1 ). These experiments were completed at both sea-level (344 m) and high altitude (3800 m). Blood pressure (finger photoplethysmography

  7. Ebullition, Plant-Mediated Transport, and Subsurface Horizontal Water Flow Dominate Methane Transport in an Arctic Sphagnum Bog

    Science.gov (United States)

    Wehr, R. A.; McCalley, C. K.; Logan, T. A.; Chanton, J.; Crill, P. M.; Rich, V. I.; Saleska, S. R.

    2017-12-01

    Emission of the greenhouse gas methane from wetlands is of prime concern in the prediction of climate change - especially emission associated with thawing permafrost, which may drive a positive feedback loop of emission and warming. In addition to the biochemistry of methane production and consumption, wetland methane emission depends critically on the transport mechanisms by which methane moves through and out of the ecosystem. We therefore developed a model of methane biochemistry and transport for a sphagnum bog representing an intermediate permafrost thaw stage in Stordalen Mire, Sweden. In order to simultaneously reproduce measured profiles of both the concentrations and isotopic compositions of both methane and carbon dioxide in the peat pore water (Fig. 1) - as well as the surface methane emission - it was necessary for the model to include ebullition, plant-mediated transport via aerenchyma, and subsurface horizontal water flow. Diffusion of gas through the pore water was relatively unimportant. As a result, 90% of the produced methane escaped the wetland rather than being consumed by methanotrophic organisms in the near-surface pore water. Our model provides a comprehensive picture of methane emission from this bog site by quantifying the vertical profiles of: acetoclastic methanogenesis, hydrogenotrophic methanogenesis, methane oxidation, aerobic respiration, ebullition, plant-mediated transport, subsurface horizontal water flow, and diffusion.

  8. NDH-Mediated Cyclic Electron Flow Around Photosystem I is Crucial for C4 Photosynthesis.

    Science.gov (United States)

    Ishikawa, Noriko; Takabayashi, Atsushi; Noguchi, Ko; Tazoe, Youshi; Yamamoto, Hiroshi; von Caemmerer, Susanne; Sato, Fumihiko; Endo, Tsuyoshi

    2016-10-01

    C 4 photosynthesis exhibits efficient CO 2 assimilation in ambient air by concentrating CO 2 around ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) through a metabolic pathway called the C 4 cycle. It has been suggested that cyclic electron flow (CEF) around PSI mediated by chloroplast NADH dehydrogenase-like complex (NDH), an alternative pathway of photosynthetic electron transport (PET), plays a crucial role in C 4 photosynthesis, although the contribution of NDH-mediated CEF is small in C 3 photosynthesis. Here, we generated NDH-suppressed transformants of a C 4 plant, Flaveria bidentis, and showed that the NDH-suppressed plants grow poorly, especially under low-light conditions. CO 2 assimilation rates were consistently decreased in the NDH-suppressed plants under low and medium light intensities. Measurements of non-photochemical quenching (NPQ) of Chl fluorescence, the oxidation state of the reaction center of PSI (P700) and the electrochromic shift (ECS) of pigment absorbance indicated that proton translocation across the thylakoid membrane is impaired in the NDH-suppressed plants. Since proton translocation across the thylakoid membrane induces ATP production, these results suggest that NDH-mediated CEF plays a role in the supply of ATP which is required for C 4 photosynthesis. Such a role is more crucial when the light that is available for photosynthesis is limited and the energy production by PET becomes rate-determining for C 4 photosynthesis. Our results demonstrate that the physiological contribution of NDH-mediated CEF is greater in C 4 photosynthesis than in C 3 photosynthesis, suggesting that the mechanism of PET in C 4 photosynthesis has changed from that in C 3 photosynthesis accompanying the changes in the mechanism of CO 2 assimilation. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Blood in the gastric lumen increases splanchnic blood flow and portal pressure in portal-hypertensive rats.

    Science.gov (United States)

    Chen, L; Groszmann, R J

    1996-10-01

    In portal-hypertensive humans, portal blood flow and pressure increase after a meal. These hemodynamic changes may increase variceal rupture risk. The aim of this study was to determine whether blood in the stomach lumen increases splanchnic flow and portal pressure (PP) in portal-hypertensive rats. superior mesenteric artery flow and PP were measured in conscious, unrestrained, fasted partial portal vein-ligated rats with chronically implanted Doppler flow probes or portal vein catheters before and after gavage with heparinized, warmed blood from donor rats, air, standard meal, or empty tube. Percentage of changes in flow and pressure from baseline were significantly greater after gavage with blood (an increase of 22.6% +/- 3.5% and an increase of 16.4% +/- 3.1%, respectively) than empty tube (an increase of 3.4% +/- 0.6% and a decrease of 5.4% +/- 3.5%, respectively) (P empty tube (P calories probably contributes to these hemodynamic changes. In patients with variceal hemorrhage, blood in the stomach may increase the risk of persistent variceal bleeding or rebleeding.

  10. Cardiorespiratory fitness modulates the acute flow-mediated dilation response following high-intensity but not moderate-intensity exercise in elderly men.

    Science.gov (United States)

    Bailey, Tom G; Perissiou, Maria; Windsor, Mark; Russell, Fraser; Golledge, Jonathan; Green, Daniel J; Askew, Christopher D

    2017-05-01

    Impaired endothelial function is observed with aging and in those with low cardiorespiratory fitness (V̇o 2peak ). Improvements in endothelial function with exercise training are somewhat dependent on the intensity of exercise. While the acute stimulus for this improvement is not completely understood, it may, in part, be due to the flow-mediated dilation (FMD) response to acute exercise. We examined the hypothesis that exercise intensity alters the brachial (systemic) FMD response in elderly men and is modulated by V̇o 2peak Forty-seven elderly men were stratified into lower (V̇o 2peak = 24.3 ± 2.9 ml·kg -1 ·min -1 ; n = 27) and higher fit groups (V̇o 2peak = 35.4 ± 5.5 ml·kg -1 ·min -1 ; n = 20) after a test of cycling peak power output (PPO). In randomized order, participants undertook moderate-intensity continuous exercise (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO) or no-exercise control. Brachial FMD was assessed at rest and 10 and 60 min after exercise. FMD increased after MICE in both groups {increase of 0.86% [95% confidence interval (CI), 0.17-1.56], P = 0.01} and normalized after 60 min. In the lower fit group, FMD was reduced after HIIE [reduction of 0.85% (95% CI, 0.12-1.58), P = 0.02] and remained decreased at 60 min. In the higher fit group, FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52% (95% CI, 0.41-2.62), P exercise control, FMD was reduced in both groups after 60 min ( P = 0.05). Exercise intensity alters the acute FMD response in elderly men and V̇o 2peak modulates the FMD response following HIIE but not MICE. The sustained decrease in FMD in the lower fit group following HIIE may represent a signal for vascular adaptation or endothelial fatigue. NEW & NOTEWORTHY This study is the first to show that moderate-intensity continuous cycling exercise increased flow-mediated dilation (FMD) transiently before normalization of FMD after 1 h, irrespective of

  11. Intravaginal Administration of Sildenafil Citrate Increases Blood Flow in the Bovine Uterus

    Directory of Open Access Journals (Sweden)

    Dzięcioł Michał

    2015-04-01

    Full Text Available The aim of the study was to evaluate the influence of sildenafil citrate administrated intravaginaly on the blood flow in the bovine uterus during dioestrus. Uterine blood flow was examined in six healthy adult cows. Sildenafil was administrated intravaginaly to each co w between the 6th and 8th d of the ovarian cycle, in the form of vaginal suppositories containing 100 mg of active substance at a dose of 100, 200, or 300 mg per animal. Uterine perfusion was estimated by the colour Doppler examination, and obtained results were analysed with the Pixel Flux Software (Chameleon, Germany. Moreover, cardiovascular parameters were also evaluated. Animals were examined before and five times after drug application (two times at 15 min intervals, and three times at 2 h intervals. A placebo suppository was also given to the cows. The analysis of the intensity and velocity of blood flow in the uterus proved that sildenafil administrated intravaginaly significantly increased blood flow in the uterus and the effect of increased perfusion was observed for 4 h and 30 min after administration. The effect of increased uterine perfusion was observed after low as well as high doses of sildenafil. Significant changes in the cardio-vascular parameters were not detected. There were no changes in the uterine perfusion as well as in cardiovascular parameters after placebo administration.

  12. Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow.

    Science.gov (United States)

    Roan, Jun-Neng; Yeh, Chin-Yi; Chiu, Wen-Cheng; Lee, Chou-Hwei; Chang, Shih-Wei; Jiangshieh, Ya-Fen; Tsai, Yu-Chuan; Lam, Chen-Fuh

    2011-01-01

    Renal blood flow (RBF) is tightly regulated by several intrinsic pathways in maintaining optimal kidney blood supply. Using a rat model of aortocaval (AC) fistula, we investigated remodeling of the renal artery following prolonged increased blood flow. An AC fistula was created in the infrarenal aorta of anesthetized rats, and changes of blood flow in the renal artery were assessed using an ultrasonic flow probe. Morphological changes and expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 in the remodeled renal artery were analyzed. Blood flow in the renal artery increased immediately after creation of AC fistula, but normal RBF was restored 8 weeks later. The renal artery dilated significantly 8 weeks after operation. Expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 was upregulated shortly after blood flow increase, and returned to baseline levels after 3 weeks. Histological sections showed luminal dilatation with medial thickening and endothelial cell-to-smooth muscle cell attachments in the remodeled renal artery. Increased RBF was accommodated by functional dilatation and remodeling in the medial layer of the renal artery in order to restore normal blood flow. Our results provide important mechanistic insight into the intrinsic regulation of the renal artery in response to increased RBF. Copyright © 2011 S. Karger AG, Basel.

  13. Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

    Science.gov (United States)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

  14. Increased sensitivity of thyroid hormone-mediated signaling despite prolonged fasting.

    Science.gov (United States)

    Martinez, Bridget; Scheibner, Michael; Soñanez-Organis, José G; Jaques, John T; Crocker, Daniel E; Ortiz, Rudy M

    2017-10-01

    Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in mammals is typically associated with reduced thyroid gland responsiveness, in an effort to suppress cellular metabolism and abate starvation. However, in prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up-regulated and TH levels are maintained with fasting duration. The function and contribution of the thyroid gland to this apparent paradox is unknown and physiologically perplexing. Here we show that the thyroid gland remains responsive during prolonged food deprivation, and that its function and production of TH increase with fasting duration in elephant seals. We discovered that our modeled plasma TH data in response to exogenous thyroid stimulating hormone predicted cellular signaling, which was corroborated independently by the enzyme expression data. The data suggest that the regulation and function of the thyroid gland in the northern elephant seal is atypical for a fasted animal, and can be better described as, "adaptive fasting". Furthermore, the modeling data help substantiate the in vivo responses measured, providing unique insight on hormone clearance, production rates, and thyroid gland responsiveness. Because these unique endocrine responses occur simultaneously with a nearly strict reliance on the oxidation of lipid, these findings provide an intriguing model to better understand the TH-mediated reliance on lipid metabolism that is not otherwise present in morbidly obese humans. When coupled with cellular, tissue-specific responses, these data provide a more integrated assessment of thyroidal status that can be extrapolated for many fasting/food deprived mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Radiological Diagnosis of Recirculatory Congenital Heart Disease with Increased Pulmonary Blood Flow

    International Nuclear Information System (INIS)

    Bartusevichiene, A.; Rulevichius, A.; Dobrovolskis, K.R.

    1995-01-01

    The number of patients with congenital diseases is increasing therefore early diagnosis of these diseases is of crucial importance. Radiological diagnostics of recirculatory congenital heart disease with increased pulmonary blood flow, i.e. atrial septal defect (ASD), ventricle septal defect (VSD), ductus arteriosus (Botalli) persistence (DAP) and atrioventricular communication (AVC) have been analysed. Recirculatory congenital heart disease with increased pulmonary blood flow (ASD, VSD, DAP)radiologically causes similar lung, lung roots and pulmonary arterial changes. After the radiomorphological and radiofunctional examination of chest organs the following symptoms of the disease were defined: all the patients had hypervolemy, enlarged structural lungs roots, enlarged pulmonary arterial arch. These radiofunctional symptoms help to differentiate congenital heart diseases case by case. (author). 7 refs., 6 figs., 1 tab

  16. The development and evaluation of a continuous flow process for the lipase-mediated oxidation of alkenes

    Directory of Open Access Journals (Sweden)

    Charlotte Wiles

    2009-06-01

    Full Text Available We report the use of an immobilised form of Candida antarctica lipase B, Novozym® 435, in a preliminary investigation into the development of a continuous flow reactor capable of performing the chemo-enzymatic oxidation of alkenes in high yield and purity, utilising the commercially available oxidant hydrogen peroxide (100 volumes. Initial investigations focussed on the lipase-mediated oxidation of 1-methylcyclohexene, with the optimised reaction conditions subsequently employed for the epoxidation of an array of aromatic and aliphatic alkenes in 97.6 to 99.5% yield and quantitative purity.

  17. Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report.

    Science.gov (United States)

    Headland, Michelle L; Clifton, Peter M; Keogh, Jennifer B

    2018-06-04

    Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

  18. The integrated model of sport confidence: a canonical correlation and mediational analysis.

    Science.gov (United States)

    Koehn, Stefan; Pearce, Alan J; Morris, Tony

    2013-12-01

    The main purpose of the study was to examine crucial parts of Vealey's (2001) integrated framework hypothesizing that sport confidence is a mediating variable between sources of sport confidence (including achievement, self-regulation, and social climate) and athletes' affect in competition. The sample consisted of 386 athletes, who completed the Sources of Sport Confidence Questionnaire, Trait Sport Confidence Inventory, and Dispositional Flow Scale-2. Canonical correlation analysis revealed a confidence-achievement dimension underlying flow. Bias-corrected bootstrap confidence intervals in AMOS 20.0 were used in examining mediation effects between source domains and dispositional flow. Results showed that sport confidence partially mediated the relationship between achievement and self-regulation domains and flow, whereas no significant mediation was found for social climate. On a subscale level, full mediation models emerged for achievement and flow dimensions of challenge-skills balance, clear goals, and concentration on the task at hand.

  19. Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

    Science.gov (United States)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.

    1993-01-01

    The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous microcirculation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, O deg, -6 deg (HDT), -12 deg, -6 deg, O deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P less than 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

  20. Bone tissue engineering: the role of interstitial fluid flow

    Science.gov (United States)

    Hillsley, M. V.; Frangos, J. A.

    1994-01-01

    It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

  1. Nasal mucosal blood flow after intranasal allergen challenge

    International Nuclear Information System (INIS)

    Holmberg, K.; Bake, B.; Pipkorn, U.

    1988-01-01

    The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133 Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated

  2. Study of male–mediated gene flow across a hybrid zone in the common shrew (Sorex araneus using Y chromosome

    Directory of Open Access Journals (Sweden)

    Andrei V. Polyakov

    2017-06-01

    Full Text Available Despite many studies, the impact of chromosome rearrangements on gene flow between chromosome races of the common shrew (Sorex araneus Linnaeus, 1758 remains unclear. Interracial hybrids form meiotic chromosome complexes that are associated with reduced fertility. Nevertheless comprehensive investigations of autosomal and mitochondrial markers revealed weak or no barrier to gene flow between chromosomally divergent populations. In a narrow zone of contact between the Novosibirsk and Tomsk races hybrids are produced with extraordinarily complex configurations at meiosis I. Microsatellite markers have not revealed any barrier to gene flow, but the phenotypic differentiation between races is greater than may be expected if gene flow was unrestricted. To explore this contradiction we analyzed the distribution of the Y chromosome SNP markers within this hybrid zone. The Y chromosome variants in combination with race specific autosome complements allow backcrosses to be distinguished and their proportion among individuals within the hybrid zone to be evaluated. The balanced ratio of the Y variants observed among the pure race individuals as well as backcrosses reveals no male mediated barrier to gene flow. The impact of reproductive unfitness of backcrosses on gene flow is discussed as a possible mechanism of the preservation of race-specific morphology within the hybrid zone.

  3. Amphiphilic mediated sample preparation for micro-flow cytometry

    Science.gov (United States)

    Clague, David S [Livermore, CA; Wheeler, Elizabeth K [Livermore, CA; Lee, Abraham P [Irvine, CA

    2009-03-17

    A flow cytometer includes a flow cell for detecting the sample, an oil phase in the flow cell, a water phase in the flow cell, an oil-water interface between the oil phase and the water phase, a detector for detecting the sample at the oil-water interface, and a hydrophobic unit operatively connected to the sample. The hydrophobic unit is attached to the sample. The sample and the hydrophobic unit are placed in an oil and water combination. The sample is detected at the interface between the oil phase and the water phase.

  4. Irradiated aromatic polysulphones of increased flow resistance and molecular weight

    International Nuclear Information System (INIS)

    Staniland, P.A.; Jarrett, W.G.

    1976-01-01

    Aromatic polymers of increased resistance to flow and molecular weight are obtained by irradiation using β-rays or γ-rays at temperatures up to 400 0 C of an aromatic polymer whose molecular chains comprise benzenoid groups and bivalent linking groups, and where irradiation is γ-rays by heating subsequent to irradiation at 200 to 400 0 C

  5. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups

    Science.gov (United States)

    Soñanez-Organis, José G.; Viscarra, Jose A.; Jaques, John T.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

    2016-01-01

    Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. PMID:26739649

  6. Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report

    Directory of Open Access Journals (Sweden)

    Michelle L. Headland

    2018-06-01

    Full Text Available Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7. All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

  7. Glial and neuronal control of brain blood flow

    DEFF Research Database (Denmark)

    Attwell, David; Buchan, Alastair M; Charpak, Serge

    2010-01-01

    Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now...... recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts...

  8. Flow-Mediated Dilatation and Asymmetric Dimethylarginine Do Not Predict Mortality in Peritoneal Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Sami Uzun

    2017-09-01

    Full Text Available Aim: Asymmetric dimethylarginine (ADMA is associated with increased coronary artery disease risk through endothelial dysfunction in dialysis patients. We aimed to investigate the role of flow-mediated dilatation (FMD, a non-invasive indicator of endothelial function, and ADMA in mortality in peritoneal dialysis (PD patients. Methods: PD patients aged 18-80 years; with dialysis duration of at least three months were included. FMD measurement and ADMA levels were recorded. Outcome of the patients on the third year were analyzed with binary logistic analyses. Results: The mean age of the 55 patients was 53±15 years and the mean follow-up duration was 36 months. Mean FMD and ADMA levels were 10.6±6.4% and 81.8±48.0 mol/L, respectively. Eighteen patients died during follow-up. Age, presence of diabetes mellitus and ischemic heart disease, ultrafiltration amount and serum albumin level were related with mortality while gender, weekly Kt/V and ADMA levels were not. There was no significant relationship between ADMA level and FMD (p=0.873. FMD was negatively correlated with systolic and diastolic blood pressures (p=0.001, p<0.001, respectively. Hypertension was found to be the most important single factor determining FMD (p=0.037. Conclusion: Estimating endothelial function by FMD or measuring serum ADMA levels may not be useful for predicting mortality in PD patients.

  9. The applied model of imagery use: Examination of moderation and mediation effects.

    Science.gov (United States)

    Koehn, S; Stavrou, N A M; Young, J A; Morris, T

    2016-08-01

    The applied model of mental imagery use proposed an interaction effect between imagery type and imagery ability. This study had two aims: (a) the examination of imagery ability as a moderating variable between imagery type and dispositional flow, and (b) the testing of alternative mediation models. The sample consisted of 367 athletes from Scotland and Australia, who completed the Sport Imagery Questionnaire, Sport Imagery Ability Questionnaire, and Dispositional Flow Scale-2. Hierarchical regression analysis showed direct effects of imagery use and imagery ability on flow, but no significant interaction. Mediation analysis revealed a significant indirect path, indicating a partially mediated relationship (P = 0.002) between imagery use, imagery ability, and flow. Partial mediation was confirmed when the effect of cognitive imagery use and cognitive imagery ability was tested, and a full mediation model was found between motivational imagery use, motivational imagery ability, and flow. The results are discussed in conjunction with potential future research directions on advancing theory and applications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans.

    Science.gov (United States)

    Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-11-15

    Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity. Copyright © 2015 the American Physiological Society.

  11. The ironic effect of guessing: increased false memory for mediated lists in younger and older adults

    Science.gov (United States)

    Coane, Jennifer H.; Huff, Mark J.; Hutchison, Keith A.

    2016-01-01

    Younger and older adults studied lists of words directly (e.g., creek, water) or indirectly (e.g., beaver, faucet) related to a nonpresented critical lure (CL; e.g., river). Indirect (i.e., mediated) lists presented items that were only related to CLs through nonpresented mediators (i.e., directly related items). Following study, participants completed a condition-specific task, math, a recall test with or without a warning about the CL, or tried to guess the CL. On a final recognition test, warnings (vs. math and recall without warning) decreased false recognition for direct lists, and guessing increased mediated false recognition (an ironic effect of guessing) in both age groups. The observed age-invariance of the ironic effect of guessing suggests that processes involved in mediated false memory are preserved in aging and confirms the effect is largely due to activation in semantic networks during encoding and to the strengthening of these networks during the interpolated tasks. PMID:26393390

  12. Characteristics of the home food environment that mediate immediate and sustained increases in child fruit and vegetable consumption: mediation analysis from the Healthy Habits cluster randomised controlled trial.

    Science.gov (United States)

    Wyse, Rebecca; Wolfenden, Luke; Bisquera, Alessandra

    2015-09-17

    The home food environment can influence the development of dietary behaviours in children, and interventions that modify characteristics of the home food environment have been shown to increase children's fruit and vegetable consumption. However to date, interventions to increase children's fruit and vegetable consumption have generally produced only modest effects. Mediation analysis can help in the design of more efficient and effective interventions by identifying the mechanisms through which interventions have an effect. This study aimed to identify characteristics of the home food environment that mediated immediate and sustained increases in children's fruit and vegetable consumption following the 4-week Healthy Habits telephone-based parent intervention. Analysis was conducted using 2-month (immediate) and 12-month (sustained) follow-up data from a cluster randomised control trial of a home food environment intervention to increase the fruit and vegetable consumption of preschool children. Using recursive path analysis, a series of mediation models were created to investigate the direct and indirect effects of immediate and sustained changes to characteristics of the home food environment (fruit and vegetable availability, accessibility, parent intake, parent providing behaviour, role-modelling, mealtime eating practices, child feeding strategies, and pressure to eat), on the change in children's fruit and vegetable consumption. Of the 394 participants in the randomised trial, 357 and 329 completed the 2- and 12-month follow-up respectively. The final mediation model suggests that the effect of the intervention on the children's fruit and vegetable consumption was mediated by parent fruit and vegetable intake and parent provision of these foods at both 2- and 12-month follow-up. Analysis of data from the Healthy Habits trial suggests that two environmental variables (parental intake and parent providing) mediate the immediate and sustained effect of the

  13. 2-methoxyestradiol-mediated anti-tumor effect increases osteoprotegerin expression in osteosarcoma cells.

    Science.gov (United States)

    Benedikt, Michaela B; Mahlum, Eric W; Shogren, Kristen L; Subramaniam, Malayannan; Spelsberg, Thomas C; Yaszemski, Michael J; Maran, Avudaiappan

    2010-04-01

    Osteosarcoma is a bone tumor that frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2-ME actions, we studied the effect of 2-ME treatment on OPG gene expression in human osteosarcoma cells. 2-ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2-ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3-, 1.9-, 2.8-, and 2.5-fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2-ME treatment. The effect of 2-ME on osteosarcoma cells was ligand-specific as parent estrogen, 17beta-estradiol and a tumorigenic estrogen metabolite, 16alpha-hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co-treating osteosarcoma cells with OPG protein did not further enhance 2-ME-mediated anti-tumor effects. OPG-released in 2-ME-treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2-ME-mediated anti-proliferative effects in osteosarcoma cells, but rather participates in anti-resorptive functions of 2-ME in bone tumor environment. Copyright 2010 Wiley-Liss, Inc.

  14. Modifying intake flow to increase EGR tolerance in an Internal Combustion Engine

    Science.gov (United States)

    Rubio, Daniel; Drabo, Mebougna; Puzinauskas, Paul

    2010-11-01

    The worldwide effort to reduce vehicle emissions and increase fuel efficiencies has continuously intensified as the need to improve air quality and reduce fuel consumption becomes more acute. Exhaust gas recirculation (EGR) is a method that has long been employed to reduce combustion temperatures and therefore reduce thermal NOx formation and accommodate higher compression ratios and more optimum combustion phasing for improved efficiency. Generally the effective EGR level as a percent of trapped charge is limited by its affect on combustion stability. Inducing flow structures such as swirl, squish and tumble in the trapped charge have proven to extend this EGR limit in homogeneous charge spark-ignited engines at part load, but this enhancement has not been significantly studied at full loads in such engines. This research explored modifying the intake flow into an engine to create tumble and evaluate its effect at high loads in such engines. This exploration included characterizing the flow on a steady flow bench and quantifying the results using engine dynamometer tests.

  15. Unleashing the Power and Energy of LiFePO4-Based Redox Flow Lithium Battery with a Bifunctional Redox Mediator.

    Science.gov (United States)

    Zhu, Yun Guang; Du, Yonghua; Jia, Chuankun; Zhou, Mingyue; Fan, Li; Wang, Xingzhu; Wang, Qing

    2017-05-10

    Redox flow batteries, despite great operation flexibility and scalability for large-scale energy storage, suffer from low energy density and relatively high cost as compared to the state-of-the-art Li-ion batteries. Here we report a redox flow lithium battery, which operates via the redox targeting reactions of LiFePO 4 with a bifunctional redox mediator, 2,3,5,6-tetramethyl-p-phenylenediamine, and presents superb energy density as the Li-ion battery and system flexibility as the redox flow battery. The battery has achieved a tank energy density as high as 1023 Wh/L, power density of 61 mW/cm 2 , and voltage efficiency of 91%. Operando X-ray absorption near-edge structure measurements were conducted to monitor the evolution of LiFePO 4 , which provides insightful information on the redox targeting process, critical to the device operation and optimization.

  16. Brachial Artery Flow-mediated Dilation Following Exercise with Augmented Oscillatory and Retrograde Shear Rate

    Directory of Open Access Journals (Sweden)

    Johnson Blair D

    2012-08-01

    Full Text Available Abstract Background Acute doses of elevated retrograde shear rate (SR appear to be detrimental to endothelial function in resting humans. However, retrograde shear increases during moderate intensity exercise which also enhances post-exercise endothelial function. Since SR patterns differ with the modality of exercise, it is important to determine if augmented retrograde SR during exercise influences post-exercise endothelial function. This study tested the hypothesis that (1 increased doses of retrograde SR in the brachial artery during lower body supine cycle ergometer exercise would attenuate post-exercise flow-mediated dilation (FMD in a dose-dependent manner, and (2 antioxidant vitamin C supplementation would prevent the attenuated post-exercise FMD response. Methods Twelve men participated in four randomized exercise sessions (90 W for 20 minutes on separate days. During three of the sessions, one arm was subjected to increased oscillatory and retrograde SR using three different forearm cuff pressures (20, 40, 60 mmHg (contralateral arm served as the control and subjects ingested placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure was performed with 1 g of vitamin C ingested prior to the session. Results Post-exercise FMD following the placebo conditions were lower in the cuffed arm versus the control arm (arm main effect: P P > 0.05. Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P P > 0.05. Conclusions These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose–response in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and

  17. Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude population.

    Science.gov (United States)

    Calderón-Gerstein, Walter S; López-Peña, Antonio; Macha-Ramírez, Raúl; Bruno-Huamán, Astrid; Espejo-Ramos, Roxana; Vílchez-Bravo, Stephany; Ramírez-Breña, María; Damián-Mucha, Milagros; Matos-Mucha, Adriana

    2017-01-01

    Endothelial function at high altitude has been measured only in populations that are genetically adapted to chronic hypoxia. The objective of this study was to evaluate endothelial dysfunction (ED) in a nongenetically adapted high-altitude population of the Andes mountains, in Huancayo, Peru (3,250 meters above sea level). Participants included 61 patients: 28 cases and 33 controls. The cases were subjects with hypertension, diabetes mellitus, obesity, or a history of stroke or coronary artery disease. Flow-mediated vasodilation (FMD) of the brachial artery was measured in the supine position, at noon, after 5 minutes of resting. The brachial artery was identified above the elbow. Its basal diameter was measured during diastole, and FMD was tested after 5 minutes of forearm ischemia. Intima-media complex in the right carotid artery was also determined. An increase in the artery's baseline diameter diabetics had ED; ED was also found in 68.8% of obese individuals, 55% of hypertensive patients, and 46.5% of controls. Age, height, body mass index, and waist diameter were higher in the cases as compared with the controls. A total of 57.9% (n=11) of the cases and 45.2% (n=19) of the controls presented ED. Patients without ED had a mean increase in brachial artery diameter of 23.16%, while in those with ED it was only 3.84%. Individuals with diabetes or hypertension had a greater thickness of the carotid artery intima media layer (1.092 versus 0.664 cm) ( p =0.037). A positive test for ED was associated with a greater basal diameter of the brachial artery (4.66±0.62 versus 4.23±0.59 cm) ( p =0.02). A total of 7 patients presented paradoxical response, developing posthyperemia vasoconstriction. The proportion of ED was high among controls and among patients with risk factors. Controls showed better FMD profiles than subjects studied in Tibet and the Himalayas.

  18. Technology and knowledge flow the power of networks

    CERN Document Server

    Trentin, Guglielmo

    2011-01-01

    This book outlines how network technology can support, foster and enhance the Knowledge Management, Sharing and Development (KMSD) processes in professional environments through the activation of both formal and informal knowledge flows. Understanding how ICT can be made available to such flows in the knowledge society is a factor that cannot be disregarded and is confirmed by the increasing interest of companies in new forms of software-mediated social interaction. The latter factor is in relation both to the possibility of accelerating internal communication and problem solving processes, an

  19. Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT

    International Nuclear Information System (INIS)

    Peng, N.J.; Tsay, D.G.; Liu, R.S.; Li, J.Y.; Kong, K.W.; Kwok, C.G.; Strauss, H.W.

    2000-01-01

    We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid. (orig.)

  20. Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

    Directory of Open Access Journals (Sweden)

    Federica Villanova

    Full Text Available Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid flow cytometry platform (CFP and a unique lyoplate-based flow cytometry platform (LFP in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10 and activation markers (Foxp3 and CD25. Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

  1. Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

    Science.gov (United States)

    Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R; Nestle, Frank O

    2013-01-01

    Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

  2. Modification of light utilization for skeletal growth by water flow in the scleractinian coral Galaxea fascicularis

    NARCIS (Netherlands)

    Schutter, M.; Kranenbarg, S.; Wijffels, R.H.; Verreth, J.A.J.; Osinga, R.

    2011-01-01

    In this study, we tested the hypothesis that the importance of water flow for skeletal growth (rate) becomes higher with increasing irradiance levels (i.e. a synergistic effect) and that such effect is mediated by a water flow modulated effect on net photosynthesis. Four series of nine nubbins of G.

  3. Lung heparan sulfates modulate Kfc during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction

    Science.gov (United States)

    Cluff, Mark; Kingston, Joseph; Hill, Denzil; Chen, Haiyan; Hoehne, Soeren; Malleske, Daniel T.; Kaur, Rajwinederjit

    2012-01-01

    Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barrier function has not been characterized. Mechanotransduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload, and mechanical ventilation. Our objective was to assess the effects of increasing vascular pressure on whole lung filtration coefficient (Kfc) and characterize the role of endothelial heparan sulfates in mediating mechanotransduction and associated increases in Kfc. Isolated perfused rat lung preparation was used to measure Kfc in response to changes in vascular pressure in combination with superimposed changes in airway pressure. The roles of heparan sulfates, nitric oxide, and reactive oxygen species were investigated. Increases in capillary pressure altered Kfc in a nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine methyl ester and heparanase III attenuated the effects of increased capillary pressure on Kfc, demonstrating active mechanotransduction leading to barrier dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated pressure-mediated increase in Kfc. Ventilation strategies altered lung NO concentration and the Kfc response to increases in vascular pressure. This is the first study to demonstrate a role for the glycocalyx in whole lung mechanotransduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status, and ventilation strategies. PMID:22160307

  4. Potential paths for male-mediated gene flow to and from an isolated grizzly bear population

    Science.gov (United States)

    Peck, Christopher P.; van Manen, Frank T.; Costello, Cecily M.; Haroldson, Mark A.; Landenburger, Lisa; Roberts, Lori L.; Bjornlie, Daniel D.; Mace, Richard D.

    2017-01-01

    For several decades, grizzly bear populations in the Greater Yellowstone Ecosystem (GYE) and the Northern Continental Divide Ecosystem (NCDE) have increased in numbers and range extent. The GYE population remains isolated and although effective population size has increased since the early 1980s, genetic connectivity between these populations remains a long-term management goal. With only ~110 km distance separating current estimates of occupied range for these populations, the potential for gene flow is likely greater now than it has been for many decades. We sought to delineate potential paths that would provide the opportunity for male-mediated gene flow between the two populations. We first developed step-selection functions to generate conductance layers using ecological, physical, and anthropogenic landscape features associated with non-stationary GPS locations of 124 male grizzly bears (199 bear-years). We then used a randomized shortest path (RSP) algorithm to estimate the average number of net passages for all grid cells in the study region, when moving from an origin to a destination node. Given habitat characteristics that were the basis for the conductance layer, movements follow certain grid cell sequences more than others and the resulting RSP values thus provide a measure of movement potential. Repeating this process for 100 pairs of random origin and destination nodes, we identified paths for three levels of random deviation (θ) from the least-cost path. We observed broad-scale concordance between model predictions for paths originating in the NCDE and those originating in the GYE for all three levels of movement exploration. Model predictions indicated that male grizzly bear movement between the ecosystems could involve a variety of routes, and verified observations of grizzly bears outside occupied range supported this finding. Where landscape features concentrated paths into corridors (e.g., because of anthropogenic influence), they typically

  5. Bone blood flow in conscious dogs at rest and during exercise

    International Nuclear Information System (INIS)

    Toendevold, E.; Buelow, J.

    1983-01-01

    Using the microsphere technique bone flow was measured in different anatomical and functional regions in long bones in conscious dogs. The measurements were performed during physical exercise upon a treadmill, and the bone blood flow values were obtained as prework resting values after 1 and 2 hours of exercise and after 1 hour of rest. The perfusion rates increased 50 per cent from 1.6 to 2.5 ml x 100 g tissue - 1 x min - 1 in the femoral and tibial cortical bones during work. In the cancelleous bone of the femoral head an increase from 12.6 to 20.6 ml x 100 g tissue - 1 x min - 1 was found. Equal flow responses were determined in the fat-filled tibia-condylar and femoral supracondylar bone. The increase took place after 2 hours' exercise, but nonstatistically verified increased perfusion was found after 1 hour's work. The alternation in bone blood flow suggest that bone has a capability of physical vasodilatation during muscular work but the flow response is slow and therefore the vasodilatation seems mediated by a metabolically induced stimulus. (author)

  6. Isolation of αL I domain mutants mediating firm cell adhesion using a novel flow-based sorting method.

    Science.gov (United States)

    Pepper, Lauren R; Parthasarathy, Ranganath; Robbins, Gregory P; Dang, Nicholas N; Hammer, Daniel A; Boder, Eric T

    2013-08-01

    The inserted (I) domain of αLβ2 integrin (LFA-1) contains the entire binding site of the molecule. It mediates both rolling and firm adhesion of leukocytes at sites of inflammation depending on the activation state of the integrin. The affinity change of the entire integrin can be mimicked by the I domain alone through mutations that affect the conformation of the molecule. High-affinity mutants of the I domain have been discovered previously using both rational design and directed evolution. We have found that binding affinity fails to dictate the behavior of I domain adhesion under shear flow. In order to better understand I domain adhesion, we have developed a novel panning method to separate yeast expressing a library of I domain variants on the surface by adhesion under flow. Using conditions analogous to those experienced by cells interacting with the post-capillary vascular endothelium, we have identified mutations supporting firm adhesion that are not found using typical directed evolution techniques that select for tight binding to soluble ligands. Mutants isolated using this method do not cluster with those found by sorting with soluble ligand. Furthermore, these mutants mediate shear-driven cell rolling dynamics decorrelated from binding affinity, as previously observed for I domains bearing engineered disulfide bridges to stabilize activated conformational states. Characterization of these mutants supports a greater understanding of the structure-function relationship of the αL I domain, and of the relationship between applied force and bioadhesion in a broader context.

  7. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Al-Khazraji, Baraa K; Mortensen, Stefan P

    2013-01-01

    During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However...... studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 µM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition...... in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation....

  8. Coronary and peripheral endothelial function in HIV patients studied with positron emission tomography and flow-mediated dilation: relation to hypercholesterolemia

    Energy Technology Data Exchange (ETDEWEB)

    Lebech, Anne-Mette [Copenhagen University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Hvidovre University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Kristoffersen, Ulrik Sloth; Kjaer, Andreas [Rigshospitalet University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); University of Copenhagen, Cluster for Molecular Imaging, Copenhagen (Denmark); Wiinberg, Niels; Petersen, Claus Leth [Frederiksberg University Hospital, Department of Clinical Physiology and Nuclear Medicine, Frederiksberg (Denmark); Kofoed, Kristian; Andersen, Ove [Copenhagen University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Copenhagen University Hospital, Clinical Research Unit, Hvidovre (Denmark); Hesse, Birger [Rigshospitalet University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); Gerstoft, Jan [Rigshospitalet University Hospital, Department of Infectious Diseases, Copenhagen (Denmark)

    2008-11-15

    The mechanisms underlying increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) are not known. Our aim was to study the endothelial function of the coronary arteries by cardiac perfusion positron emission tomography (PET), in HIV patients with normal or high cholesterol levels. Flow mediated dilation (FMD) of the brachial artery and circulating endothelial markers were also assessed. HIV patients in ART with total cholesterol {<=} 5.5 mmol/L (215 mg/dL; n = 13) or total cholesterol {>=} 6.5 mmol/L (254 mg/dL; n = 12) and healthy controls (n = 14) were included. {sup 13}NH{sub 3} perfusion PET, FMD, and measurement of plasma levels of E-Selectin, ICAM-1, VCAM-1, tPAI-1, and hs-CRP were performed. Baseline myocardial perfusion and the coronary flow reserve measured by PET (3.2 {+-} 0.3, 3.2 {+-} 0.3 and 3.0 {+-} 0.3; ns) was similar in HIV patients with normal or high total cholesterol and controls. FMD did not differ between the groups and was 4.6 {+-} 1.1%, 5.1 {+-} 1.2%, and 4.6 {+-} 0.8%, respectively. Increased levels of plasma E-Selectin, ICAM-1, tPAI-1, and hs-CRP were found in HIV patients when compared to controls (p < 0.05). E-Selectin and ICAM-1 levels were higher in HIV patients receiving protease inhibitors (PI) compared to those not receiving PI (p < 0.05). None of the measured endothelial biomarkers differed between the normal and high cholesterol HIV groups. In ART-treated HIV patients with a low overall cardiovascular risk, no sign of endothelial dysfunction was found not even in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia. (orig.)

  9. NADPH oxidase 4-derived superoxide mediates flow-stimulated NKCC2 activity in thick ascending limbs.

    Science.gov (United States)

    Saez, Fara; Hong, Nancy J; Garvin, Jeffrey L

    2018-05-01

    Luminal flow augments Na + reabsorption in the thick ascending limb more than can be explained by increased ion delivery. This segment reabsorbs 30% of the filtered load of Na + , playing a key role in its homeostasis. Whether flow elevations enhance Na + -K + -2Cl - cotransporter (NKCC2) activity and the second messenger involved are unknown. We hypothesized that raising luminal flow augments NKCC2 activity by enhancing superoxide ([Formula: see text]) production by NADPH oxidase 4 (NOX4). NKCC2 activity was measured in thick ascending limbs perfused at either 5 or 20 nl/min with and without inhibitors of [Formula: see text] production. Raising luminal flow from 5 to 20 nl/min enhanced NKCC2 activity from 4.8 ± 0.9 to 6.3 ± 1.2 arbitrary fluorescent units (AFU)/s. Maintaining flow at 5 nl/min did not alter NKCC2 activity. The superoxide dismutase mimetic manganese (III) tetrakis (4-benzoic acid) porphyrin chloride blunted NKCC2 activity from 3.5 ± 0.4 to 2.5 ± 0.2 AFU/s when flow was 20 nl/min but not 5 nl/min. When flow was 20 nl/min, NKCC2 activity showed no change with time. The selective NOX1/4 inhibitor GKT-137831 blunted NKCC2 activity when thick ascending limbs were perfused at 20 nl/min from 7.2 ± 1.1 to 4.5 ± 0.8 AFU/s but not at 5 nl/min. The inhibitor also prevented luminal flow from elevating [Formula: see text] production. Allopurinol, a xanthine oxidase inhibitor, had no effect on NKCC2 activity when flow was 20 nl/min. Tetanus toxin prevents flow-induced stimulation of NKCC2 activity. We conclude that elevations in luminal flow enhance NaCl reabsorption in thick ascending limbs by stimulating NKCC2 via NOX4 activation and increased [Formula: see text]. NKCC2 activation is primarily the result of insertion of new transporters in the membrane.

  10. Shear rate normalization is not essential for removing the dependency of flow-mediated dilation on baseline artery diameter: past research revisited

    International Nuclear Information System (INIS)

    Atkinson, Greg

    2014-01-01

    A ratio index (FMD%) is used ubiquitously to scale (by simple division) brachial artery flow-mediated dilation (D diff ) in direct proportion to baseline diameter (D base ). It is now known that D diff is inversely proportional to D base rendering FMD% wholly inappropriate. Consequently, FMD% is still substantially dependent on D base . Although this problem is grounded in statistics, normalization of FMD% for the change in arterial shear rate (ΔSR) has been proposed to remove this D base -dependency. It was hypothesized that, if the flow-mediated response is scaled properly to D base in the first place, shear rate normalization would not be needed to remove D base -dependency. Dedicated software (Digitizelt) was employed to extract the data from a seminal study on FMD% normalization. The underlying allometric relationship between D base and peak diameter (D peak ) was described. The re-analyses revealed that the absolute change in arterial diameter was strongly inversely proportional to D base (r= − 0.7, P < 0.0005). The allometric exponent for the D base –D peak relationship was 0.82 (95% CI: 0.78–0.86) rather than the value of 1 needed for appropriate use of FMD%. The allometric approach completely eliminated the originally reported dependency on D base without any need for ΔSR normalization (r=0.0, P=0.96). The correlation between ΔSR and FMD% reduced from 0.69 to 0.37, when adjusted for D base . In conclusion, this new re-analysis of data from an influential study demonstrates that the FMD%–D base correlation is caused by the inappropriate size-scaling properties of FMD% itself. Removal of D base -dependency via FMD%/ΔSR normalization is not essential at all if allometric scaling is applied to isolate the flow-mediated response in the first place. Consequently, the influence of ΔSR on this properly scaled response can also be isolated and quantified accurately without the confounding influence of D base . (paper)

  11. Chronic hydrocephalus-induced changes in cerebral blood flow: mediation through cardiac effects.

    Science.gov (United States)

    Dombrowski, Stephen M; Schenk, Soren; Leichliter, Anna; Leibson, Zack; Fukamachi, Kiyotaka; Luciano, Mark G

    2006-10-01

    Decreased cerebral blood flow (CBF) in hydrocephalus is believed to be related to increased intracranial pressure (ICP), vascular compression as the result of enlarged ventricles, or impaired metabolic activity. Little attention has been given to the relationship between cardiac function and systemic blood flow in chronic hydrocephalus (CH). Using an experimental model of chronic obstructive hydrocephalus developed in our laboratory, we investigated the relationship between the duration and severity of hydrocephalus and cardiac output (CO), CBF, myocardial tissue perfusion (MTP), and peripheral blood flow (PBF). Blood flow measures were obtained using the microsphere injection method under controlled hemodynamic conditions in experimental CH (n=23) and surgical control (n=8) canines at baseline and at 2, 4, 8, 12, and 16 weeks. Cardiac output measures were made using the Swan-Ganz thermodilution method. Intracranial compliance (ICC) via cerebrospinal fluid (CSF) bolus removal and infusion, and oxygen delivery in CSF and prefrontal cortex (PFC) were also investigated. We observed an initial surgical effect relating to 30% CO reduction and approximately 50% decrease in CBF, MTP, and PBF in both groups 2 weeks postoperatively, which recovered in control animals but continued to decline further in CH animals at 16 weeks. Cerebral blood flow, which was positively correlated with CO (P=0.028), showed no significant relationship with either CSF volume or pressure. Decreased CBF correlated with oxygen deprivation in PFC (P=0.006). Cardiac output was inversely related with ventriculomegaly (P=0.019), but did not correlate with ICP. Decreased CO corresponded to increased ICC, as measured by CSF infusion (P=0.04). Our results suggest that CH may have more of an influence on CO and CBF in the chronic stage than in the early condition, which was dominated by surgical effect. The cause of this late deterioration of cardiac function in hydrocephalus is uncertain, but may reflect

  12. Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia-reperfusion in humans.

    Science.gov (United States)

    Schreuder, Tim H A; Eijsvogels, Thijs M H; Greyling, Arno; Draijer, Richard; Hopman, Maria T E; Thijssen, Dick H J

    2014-02-01

    Tea consumption is associated with reduced cardiovascular risk. Previous studies found that tea flavonoids work through direct effects on the vasculature, leading to dose-dependent improvements in endothelial function. Cardioprotective effects of regular tea consumption may relate to the prevention of endothelial ischaemia-reperfusion (IR) injury. Therefore, we examined the effect of black tea consumption on endothelial function and the ability of tea to prevent IR injury. In a randomized, crossover study, 20 healthy subjects underwent 7 days of tea consumption (3 cups per day) or abstinence from tea. We examined brachial artery (BA) endothelial function via flow-mediated dilation (FMD), using high resolution echo-Doppler, before and 90 min after tea or hot water consumption. Subsequently, we followed a 20-min ischaemia and 20-min reperfusion protocol of the BA after which we measured FMD to examine the potential of tea consumption to protect against IR injury. Tea consumption resulted in an immediate increase in FMD% (pre-consumption: 5.8 ± 2.5; post-consumption: 7.2 ± 3.2; p FMD (p FMD. However, the impact of the IR protocol on FMD was not influenced by tea consumption. Therefore, the cardioprotective association of tea ingestion relates to a direct effect of tea on the endothelium in humans in vivo.

  13. Pollen-mediated gene flow in wheat (Triticum aestivum L.) in a semiarid field environment in Spain.

    Science.gov (United States)

    Loureiro, Iñigo; Escorial, María-Concepción; González, Águeda; Chueca, María-Cristina

    2012-12-01

    Transgenic wheat (Triticum aestivum L.) varieties are being developed and field-tested in various countries. Concerns regarding gene flow from genetically modified (GM) crops to non-GM crops have stimulated research to estimate outcrossing in wheat prior to the release and commercialization of any transgenic cultivars. The aim is to ensure that coexistence of all types of wheat with GM wheat is feasible in accordance with current regulations. The present study describes the result of a field experiment under the semi-arid climate conditions of Madrid, Spain, at two locations ("La Canaleja" and "El Encin" experimental stations) in Madrid over a 3-year period, from 2005 to 2007. The experimental design consisted of a 50 × 50 m wheat pollen source sown with wheat cultivars resistant to the herbicide chlortoluron ('Deganit' and 'Castan' respectively) and three susceptible receptor cultivars ('Abental', 'Altria' and 'Recital') sown in replicated 1 × 1 m plots at different distances (0, 1, 3, 5, 10, 20, 40, 80 and 100 m) and four directions. Outcrossing rates were measured as a percentage of herbicide-resistant hybrids using an herbicide-screening assay. Outcrossing was greatest near the pollen source, averaging 0.029% at 0 m distance at "La Canaleja" and 0.337% at "El Encin", both below the 0.9% European Union regulated threshold, although a maximum outcrossing rate of 3.5% was detected in one recipient plot. These percentages declined rapidly as the distance increased, but hybrids were detected at different rates at distances of up to 100 m, the maximum distance of the experiment. Environmental conditions, as drought in 2004-2005 and 2005-2006, may have influenced the extent of outcrossing. These assays carried out in wheat under semi-arid conditions in Europe provide a more complete assessment of pollen-mediated gene flow in this crop.

  14. Application of PSAT to Load Flow Analysis with STATCOM under Load Increase Scenario and Line Contingencies

    Science.gov (United States)

    Telang, Aparna S.; Bedekar, P. P.

    2017-09-01

    Load flow analysis is the initial and essential step for any power system computation. It is required for choosing better options for power system expansion to meet with ever increasing load demand. Implementation of Flexible AC Transmission System (FACTS) device like STATCOM, in the load flow, which is having fast and very flexible control, is one of the important tasks for power system researchers. This paper presents a simple and systematic approach for steady state power flow calculations with FACTS controller, static synchronous compensator (STATCOM) using command line usage of MATLAB tool-power system analysis toolbox (PSAT). The complexity of MATLAB language programming increases due to incorporation of STATCOM in an existing Newton-Raphson load flow algorithm. Thus, the main contribution of this paper is to show how command line usage of user friendly MATLAB tool, PSAT, can extensively be used for quicker and wider interpretation of the results of load flow with STATCOM. The novelty of this paper lies in the method of applying the load increase pattern, where the active and reactive loads have been changed simultaneously at all the load buses under consideration for creating stressed conditions for load flow analysis with STATCOM. The performance have been evaluated on many standard IEEE test systems and the results for standard IEEE-30 bus system, IEEE-57 bus system, and IEEE-118 bus system are presented.

  15. Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats.

    Directory of Open Access Journals (Sweden)

    Hong-Hai Zhang

    Full Text Available Mechanisms associated with cyclin-dependent kinase 5 (Cdk5-mediated heat hyperalgesia induced by inflammation remain undefined. This study was designed to examine whether Cdk5 mediates heat hyperalgesia resulting from peripheral injection of complete Freund's adjuvant (CFA in the spinal dorsal horns of rats by interacting with synaptophysin, a well known membrane protein mediating the endocytosis-exocytosis cycle of synaptic vesicles as a molecular marker associated with presynaptic vesicle membranes. The role of Cdk5 in mediating synaptophysin was examined through the combined use of behavioral approaches, imaging studies, and immunoprecipitation following CFA-induced inflammatory pain. Results showed that Cdk5 colocalized with both synaptophysin and soluble N-ethylmaleimide-sensitive factor (NSF attachment protein receptors (SNAREs consisting of VAMP-2, SNAP-25, and syntaxin 1A in spinal dorsal horn of rats. Increased synaptophysin expression of spinal cord horn neurons post intraplantar injection of CFA coincided with increased duration of heat hyperalgesia lasting from 6 h to 3 d. Intrathecal administration of roscovitine, a Cdk5 specific inhibitor, significantly depressed synaptophysin expression during peak heat hyperalgesia and heat hyperalgesia induced by peripheral injection of CFA. Data presented in this report indicated that calpain activity was transiently upregulated 6 h post CFA-treatment despite previous reports suggesting that calpain was capable of cleaving p35 into p25. Results from previous studies obtained by other laboratories demonstrated that significant changes in p35 expression levels within spinal cord horn neurons were not observed in the CFA-treated inflammatory pain model although significant upregulation of Cdk5 kinase was observed between 2 h to 7 d. Therefore, generation of p25 occurred in a calpain-independent fashion in a CFA-treated inflammatory pain model. Our results demonstrated that increased synaptophysin

  16. Central and peripheral blood flow during exercise with a continuous-flow left ventricular assist device: constant versus increasing pump speed: a pilot study

    DEFF Research Database (Denmark)

    Brassard, Patrice; Jensen, Annette S; Nordsborg, Nikolai

    2011-01-01

    with work rate would increase organ blood flow. Methods and Results- Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients...

  17. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  18. Evidence for water-mediated mechanisms in coral–algal interactions

    Science.gov (United States)

    Jorissen, Hendrikje; Skinner, Christina; Osinga, Ronald; de Beer, Dirk

    2016-01-01

    Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral–algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations at the coral–algal interface vary with algal competitors and competitiveness. Using field observations and microsensor measurements in a flow chamber, we show that coral (massive Porites) interfaces with thick turf algae, macroalgae, and cyanobacteria, which are successful competitors against coral in the field, are characterized by a thick DBL and hypoxia at night. In contrast, coral interfaces with crustose coralline algae, conspecifics, and thin turf algae, which are poorer competitors, have a thin DBL and low hypoxia at night. Furthermore, DBL thickness and hypoxia at the interface with turf decreased with increasing flow speed, but not when thick turf was upstream. Our results support the importance of water-mediated transport mechanisms in coral–algal interactions. Shifts towards algal dominance, particularly dense assemblages, may lead to thicker DBLs, higher hypoxia, and higher concentrations of harmful metabolites and pathogens along coral borders, which in turn may facilitate algal overgrowth of live corals. These effects may be mediated by flow speed and orientation. PMID:27512146

  19. The Development of Visible-Light Photoredox Catalysis in Flow.

    Science.gov (United States)

    Garlets, Zachary J; Nguyen, John D; Stephenson, Corey R J

    2014-04-01

    Visible-light photoredox catalysis has recently emerged as a viable alternative for radical reactions otherwise carried out with tin and boron reagents. It has been recognized that by merging photoredox catalysis with flow chemistry, slow reaction times, lower yields, and safety concerns may be obviated. While flow reactors have been successfully applied to reactions carried out with UV light, only recent developments have demonstrated the same potential of flow reactors for the improvement of visible-light-mediated reactions. This review examines the initial and continuing development of visible-light-mediated photoredox flow chemistry by exemplifying the benefits of flow chemistry compared with conventional batch techniques.

  20. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Science.gov (United States)

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Science.gov (United States)

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  2. Subclinical Markers of Cardiovascular Disease Among Police Officers: A Longitudinal Assessment of the Cortisol Awakening Response and Flow Mediated Artery Dilation.

    Science.gov (United States)

    Violanti, John M; Fekedulegn, Desta; Andrew, Michael E; Charles, Luenda E; Gu, Ja K; Miller, Diane B

    2018-05-07

    To examine the association of the cortisol awakening response (CAR) with change in brachial artery flow-mediated dilation (FMD%) in police officers over a seven-year period. Baseline CAR was obtained from four saliva samples taken fifteen minutes apart immediately after awakening. Analysis of covariance was used to compare the change in FMD% (FMD%Follow-up-FMD%Baseline) across tertiles of area under the cortisol curve with respect to increase (AUCI). Regression analysis was use to assess trend. Officers (n = 172; 81% men) had a mean ± SD age of 41 ± 7.6 years. Men in the lowest AUCI tertile (i.e., atypical waking cortisol pattern) had a significantly larger seven-year mean decline in FMD% (mean ± SE: -2.56 ± 0.64) compared to men in the highest tertile (-0.89 ± 0.69) (p = 0.0087). An awakening cortisol AUCI predicted worsening of FMD% approximately seven years later among male officers.

  3. Laminar shear flow increases hydrogen sulfide and activates a nitric oxide producing signaling cascade in endothelial cells.

    Science.gov (United States)

    Huang, Bin; Chen, Chang-Ting; Chen, Chi-Shia; Wang, Yun-Ming; Hsieh, Hsyue-Jen; Wang, Danny Ling

    2015-09-04

    Laminar shear flow triggers a signaling cascade that maintains the integrity of endothelial cells (ECs). Hydrogen sulfide (H2S), a new gasotransmitter is regarded as an upstream regulator of nitric oxide (NO). Whether the H2S-generating enzymes are correlated to the enzymes involved in NO production under shear flow conditions remains unclear as yet. In the present study, the cultured ECs were subjected to a constant shear flow (12 dyn/cm(2)) in a parallel flow chamber system. We investigated the expression of three key enzymes for H2S biosynthesis, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercapto-sulfurtransferase (3-MST). Shear flow markedly increased the level of 3-MST. Shear flow enhanced the production of H2S was determined by NBD-SCN reagent that can bind to cysteine/homocystein. Exogenous treatment of NaHS that can release gaseous H2S, ECs showed an increase of phosphorylation in Akt(S473), ERK(T202/Y204) and eNOS(S1177). This indicated that H2S can trigger the NO-production signaling cascade. Silencing of CSE, CBS and 3-MST genes by siRNA separately attenuated the phosphorylation levels of Akt(S473) and eNOS(S1177) under shear flow conditions. The particular mode of shear flow increased H2S production. The interplay between H2S and NO-generating enzymes were discussed in the present study. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Flow-mediated dilatation has no independent prognostic effect in patients with chest pain with or without ischaemic heart disease

    DEFF Research Database (Denmark)

    Ulriksen, Line Skjold; Malmqvist, Beata B; Hansen, Are

    2009-01-01

    OBJECTIVE: The purpose of this study was to assess the prognostic effect of flow-mediated dilatation (FMD) in patients with chest pain admitted to a coronary care unit. METHODS: Endothelium-dependent FMD in the brachial artery was examined in 223 patients with acute chest pain. All patients...... underwent a stress test at the time of admittance. On the basis of a positive stress test, a prior myocardial infarction (MI), prior percutaneous coronary intervention (PCI) or coronary bypass surgery (CABG), 137 patients were categorized as having ischaemic heart disease (IHD). RESULTS: Patients with IHD...

  5. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Numerical study on increasing mass flow ratio by energy deposition of high frequency pulsed laser

    International Nuclear Information System (INIS)

    Wang Diankai; Hong Yanji; Li Qian

    2013-01-01

    The mass flow ratio (MFR) of air breathing ramjet inlet would be decreased, when the Mach number is lower than the designed value. High frequency pulsed laser energy was deposited upstream of the cowl lip to reflect the stream so as to increase the MFR. When the Mach number of the flow was 5.0, and the static pressure and temperature of the flow were 2 551.6 Pa and 116.7 K, respectively, two-dimensional non-stationary compressible RANS equations were solved with upwind format to study the mechanisms of increasing MFR by high frequency pulsed laser energy deposition. The laser deposition frequency was 100 kHz and the average power was 500 W. The crossing point of the first forebody oblique shock and extension line of cowl lip was selected as the expected point. Then the deposition position was optimized by searching near the expected point. The results indicate that with the optimization of laser energy deposition position, the MFR would be increased from 63% to 97%. The potential value of increasing MFR by high frequency pulsed laser energy deposition was proved. The method for selection of the energy deposition position was also presented. (authors)

  7. Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans.

    Science.gov (United States)

    Monahan, Kevin D

    2012-11-15

    Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Increasing the Dynamic Range of Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Villagómez Hoyos, Carlos Armando; Stuart, Matthias Bo; Jensen, Jørgen Arendt

    2014-01-01

    images. The emissions for the two imaging modes are interleaved 1-to-1 ratio, providing a high frame rate equal to the effective pulse repetition frequency of each imaging mode. The direction of the flow is estimated, and the velocity is then determined in that direction. This method Works for all angles...... standard deviations are 1.59% and 6.12%, respectively. The presented method can improve the estimates by synthesizing a lower pulse repetition frequency, thereby increasing the dynamic range of the vector velocity imaging....

  9. Converting to increased Tc-99m DTPA renal flow from slight decrease in renal flow following angioplastic procedures in a patient with unequal renal artery stenoses

    International Nuclear Information System (INIS)

    Shih Weijen; Mitchell, B.L.

    1990-01-01

    The use of Tc-99m DTPA renal flow imaging has increased in importance since the introduction of catheter angioplasty. The high diagnostic accuracy and non-invasive technique as compared to digital subtraction angiography have done much to enhance its usage in the evaluation of renal functional status. This paper reports Tc-99m DTPA renal flow imaging findings before and after angioplasty in a patient with bilateral renal artery stenosis. The slight decrease in Tc-99m DTPA renal flow on the kidney before angioplasty converted to an increase in flow on the right kidney after angioplasty. Post procedural blood flow was much higher on the right, where stenosis was previously more severe. It is hypothesized that the right kidney was protected from elevated aterial pressure by its 90% arterial stenosis while the left kidney was exposed to elevated systemic blood pressure. Because of vascular damage to the unprotected left kidney, post-angioplasty blood flow was less in the left kidney than in the ischemic but protected right kidney. (orig.) [de

  10. Estimation of Indirect Effects in the Presence of Unmeasured Confounding for the Mediator-Outcome Relationship in a Multilevel 2-1-1 Mediation Model

    Science.gov (United States)

    Talloen, Wouter; Moerkerke, Beatrijs; Loeys, Tom; De Naeghel, Jessie; Van Keer, Hilde; Vansteelandt, Stijn

    2016-01-01

    To assess the direct and indirect effect of an intervention, multilevel 2-1-1 studies with intervention randomized at the upper (class) level and mediator and outcome measured at the lower (student) level are frequently used in educational research. In such studies, the mediation process may flow through the student-level mediator (the within…

  11. Aromatic polymers of increased resistance to flow and molecular weight obtained by irradiation

    International Nuclear Information System (INIS)

    Staniland, P.A.; Jarrett, G.

    1976-01-01

    Aromatic polymers of increased resistance to flow and increased molecular weight are obtained by irradiation using β rays or gamma rays at temperatures up to 400 0 C of an aromatic polymer whose molecular chains comprise benzenoid groups and bivalent linking groups, and where irradiation is gamma rays by heating subsequent to irradiation at 200 0 C to 400 0 C. The polymeric materials having increased molecular weight are useful for coating non-cooking surfaces of cookware

  12. PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns.

    Science.gov (United States)

    Thomas, James A; Deaton, Rebecca A; Hastings, Nicole E; Shang, Yueting; Moehle, Christopher W; Eriksson, Ulf; Topouzis, Stavros; Wamhoff, Brian R; Blackman, Brett R; Owens, Gary K

    2009-02-01

    Platelet-derived growth factor (PDGF)-BB is a well-known smooth muscle (SM) cell (SMC) phenotypic modulator that signals by binding to PDGF alphaalpha-, alphabeta-, and betabeta-membrane receptors. PDGF-DD is a recently identified PDGF family member, and its role in SMC phenotypic modulation is unknown. Here we demonstrate that PDGF-DD inhibited expression of multiple SMC genes, including SM alpha-actin and SM myosin heavy chain, and upregulated expression of the potent SMC differentiation repressor gene Kruppel-like factor-4 at the mRNA and protein levels. On the basis of the results of promoter-reporter assays, changes in SMC gene expression were mediated, at least in part, at the level of transcription. Attenuation of the SMC phenotypic modulatory activity of PDGF-DD by pharmacological inhibitors of ERK phosphorylation and by a small interfering RNA to Kruppel-like factor-4 highlight the role of these two pathways in this process. PDGF-DD failed to repress SM alpha-actin and SM myosin heavy chain in mouse SMCs lacking a functional PDGF beta-receptor. Importantly, PDGF-DD expression was increased in neointimal lesions in the aortic arch region of apolipoprotein C-deficient (ApoE(-/-)) mice. Furthermore, human endothelial cells exposed to an atherosclerosis-prone flow pattern, as in vascular regions susceptible to the development of atherosclerosis, exhibited a significant increase in PDGF-DD expression. These findings demonstrate a novel activity for PDGF-DD in SMC biology and highlight the potential contribution of this molecule to SMC phenotypic modulation in the setting of disturbed blood flow.

  13. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    International Nuclear Information System (INIS)

    Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A.

    1992-01-01

    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: 1) increased negative intrathoracic pressure swings (-25±1 cmH 2 O) induced by an inspiratory resistance; 2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and 3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au)

  14. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))

    1992-01-01

    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

  15. The role of bed surface configuration on river response under increasing flows

    Science.gov (United States)

    Ferrer-Boix, Carles; Elgueta, María A.; Hassan, Marwan A.

    2017-04-01

    This research aims to explore how bed surface configuration influence channel evolution, vertical and downstream sediment sorting, and sediment transport in gravel bed streams under varying flows. While a significant body of research has been focused on channel evolution under constant flow regimes, few studies have focused on the impacts of flow variations in channel adjustments. Particularly, we are interested in examining the impact of the degree of bed surface coarsening and particle arrangement on channel adjustments and sediment transport rates. To this end, we conducted a set of experiments in a 0.55 m-wide, 5 m-long tilting flume. Flow discharge during the runs was initially held constant at 25 l/s for a period of time after which discharge was gradually increased at steps of certain duration. Flow rates during the rising limb of the hydrographs ranged from 26 l/s to 40 l/s. Initial bed slope was 0.04 m/m for all runs. Some of the experiments were conducted under no feed conditions while others were carried out with sediment supply, which ranged from 1 kg/h to 10 kg/h. The feed texture in these latter runs was identical to that of the original mixture (Dg = 5.65 mm and σg = 3.05). Bed slopes and surface configuration were obtained after varying times of conditioning under constant flow and no feed. Data acquisition included: 1) bed surface images covering the entire flume, 2) bed scans at 2 mm resolution of the whole flume and 3) real-time measurements of bedload transport (rate and texture) at the outlet of the flume. This set up allows us to obtain fractional particle mobility, i.e. how much bed area covered by a particular grain size changed at a given time and to link to sediment transport rates. Data gathered from this study 1) will contribute to better understanding of river dynamics under unsteady flow conditions (floods) and 2) will help us improve sediment transport predictions under such conditions.

  16. Increase of body surface temperature and blood flow by theanine

    International Nuclear Information System (INIS)

    Hasegawa, Takeo; Noguchi, Kenichi; Ando, Satoshi

    2002-01-01

    Suntheanine (Taiyo Kagaku Co.: Theanine) is the trade name for L-theanine which is a unique amino acid found almost solely in tea plants, responsible for the exotictaste of green tea. We investigated the effects of relate to relaxation, improves the taste of processed foods, radiation sensitization, and increase of body surface temperature in vivo study. The results of the present study confirmed, (1) Suntheanine is incorporated into the brain and induces the emission of α -waves an induced of relaxation. (2) Body surface temperature and blood flow on skin were increased after administration of Suntheanine. (3) There was effects of radiation sensitization in whole body irradiation of X-rays after Suntheanine IP injection on C3H mice. (4) Acute toxicity, subacute toxicity and mutagen testconfirm the safety Suntheanine in this study

  17. Transient heat transfer for helium gas flowing over a horizontal cylinder with exponentially increasing heat input

    International Nuclear Information System (INIS)

    Liu, Qiusheng; Fukuda, Katsuya

    2003-01-01

    The transient heat transfer coefficients for forced convection flow of helium gas over a horizontal cylinder were measured under wide experimental conditions. The platinum cylinder with a diameter of 1.0 mm was used as test heater and heated by electric current with an exponentially increasing heat input of Q 0 exp(t/τ). The gas flow velocities ranged from 5 to 35 m/s, the gas temperatures ranged from 25 to 80degC, and the periods of heat generation rate, τ, ranged from 40 ms to 20 s. The surface superheat and heat flux increase exponentially as the heat generation rate increases with the exponential function. It was clarified that the heat transfer coefficient approaches the quasi-steady-state one for the period τ longer than about 1 s, and it becomes higher for the period shorter than around 1 s. The transient heat transfer shows less dependence on the gas flowing velocity when the period becomes very shorter. The gas temperature in this study shows little influence on the heat transfer coefficient. Semi-empirical correlation for quasi-steady-state heat transfer was obtained based on the experimental data. The ratios of transient Nusselt number Nu tr to quasi-steady-state Nusselt number Nu st at various periods, flow velocities, and gas temperatures were obtained. The heat transfer shifts to the quasi-steady-state heat transfer for longer periods and shifts to the transient heat transfer for shorter periods at the same flow velocity. It also approaches the quasi-steady-state one for higher flow velocity at the same period. Empirical correlation for transient heat transfer was also obtained based on the experimental data. (author)

  18. ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage.

    Science.gov (United States)

    Karayazi Atici, Ödül; Urbanska, Anna; Gopinathan, Sesha Gopal; Boutillon, Florence; Goffin, Vincent; Shemanko, Carrie S

    2018-02-01

    Prolactin (PRL) acts as a survival factor for breast cancer cells, but the PRL signaling pathway and the mechanism are unknown. Previously, we identified the master chaperone, heat shock protein 90 (HSP90) α, as a prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of PRL-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase (ATM) protein plays a critical role in the cellular response to double-strand DNA damage. We observed that PRL increased viability of breast cancer cells treated with doxorubicin or etoposide. The increase in cellular resistance is specific to the PRL receptor, because the PRL receptor antagonist, Δ1-9-G129R-hPRL, prevented the increase in viability. Two different HSP90 inhibitors, 17-allylamino-17-demethoxygeldanamycin and BIIB021, reduced the PRL-mediated increase in cell viability of doxorubicin-treated cells and led to a decrease in JAK2, ATM, and phosphorylated ATM protein levels. Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the PRL-mediated increase in cell viability of DNA-damaged cells, supporting the involvement of each, as well as the crosstalk of ATM with the PRL pathway in the context of DNA damage. Drug synergism was detected between the ATM inhibitor (KU55933) and doxorubicin and between the HSP90 inhibitor (BIIB021) and doxorubicin. Short interfering RNA directed against ATM prevented the PRL-mediated increase in cell survival in two-dimensional cell culture, three-dimensional collagen gel cultures, and clonogenic cell survival, after doxorubicin treatment. Our results indicate that ATM contributes to the PRL-JAK2-STAT5-HSP90 pathway in mediating cellular resistance to DNA-damaging agents. Copyright © 2018 Endocrine Society.

  19. Acute extracellular fluid volume changes increase ileocolonic resistance to saline flow in anesthetized dogs

    Directory of Open Access Journals (Sweden)

    Santiago Jr. A.T.

    1997-01-01

    Full Text Available We determined the effect of acute extracellular fluid volume changes on saline flow through 4 gut segments (ileocolonic, ileal, ileocolonic sphincter and proximal colon, perfused at constant pressure in anesthetized dogs. Two different experimental protocols were used: hypervolemia (iv saline infusion, 0.9% NaCl, 20 ml/min, volume up to 5% body weight and controlled hemorrhage (up to a 50% drop in mean arterial pressure. Mean ileocolonic flow (N = 6 was gradually and significantly decreased during the expansion (17.1%, P<0.05 and expanded (44.9%, P<0.05 periods while mean ileal flow (N = 7 was significantly decreased only during the expanded period (38%, P<0.05. Mean colonic flow (N = 7 was decreased during expansion (12%, P<0.05 but returned to control levels during the expanded period. Mean ileocolonic sphincter flow (N = 6 was not significantly modified. Mean ileocolonic flow (N = 10 was also decreased after hemorrhage (retracted period by 17% (P<0.05, but saline flow was not modified in the other separate circuits (N = 6, 5 and 4 for ileal, ileocolonic sphincter and colonic groups, respectively. The expansion effect was blocked by atropine (0.5 mg/kg, iv both on the ileocolonic (N = 6 and ileal (N = 5 circuits. Acute extracellular fluid volume retraction and expansion increased the lower gastrointestinal resistances to saline flow. These effects, which could physiologically decrease the liquid volume being supplied to the colon, are possible mechanisms activated to acutely balance liquid volume deficit and excess.

  20. Flow experience in teams: The role of shared leadership.

    Science.gov (United States)

    Aubé, Caroline; Rousseau, Vincent; Brunelle, Eric

    2018-04-01

    The present study tests a multilevel mediation model concerning the effect of shared leadership on team members' flow experience. Specifically, we investigate the mediating role of teamwork behaviors in the relationships between 2 complementary indicators of shared leadership (i.e., density and centralization) and flow. Based on a multisource approach, we collected data through observation and survey of 111 project teams (521 individuals) made up of university students participating in a project management simulation. The results show that density and centralization have both an additive effect and an interaction effect on teamwork behaviors, such that the relationship between density and teamwork behaviors is stronger when centralization is low. In addition, teamwork behaviors play a mediating role in the relationship between shared leadership and flow. Overall, the findings highlight the importance of promoting team-based shared leadership in organizations to favor the flow experience. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Glucagon-like peptide-2 increases mesenteric blood flow in humans

    DEFF Research Database (Denmark)

    Bremholm, Lasse; Hornum, Mads; Henriksen, Birthe Merete

    2008-01-01

    a significant association between IV and SC administration of synthetic GLP-2 and changes in mesenteric blood flow. An exponential dose-response relationship was observed after IV infusion. The meal-induced changes in mesenteric blood flow over time were similar to those obtained by SC GLP-2. Thus, our results......OBJECTIVE: Mesenteric blood flow is believed to be influenced by digestion and absorption of ingested macronutrients. We hypothesized that the intestinotrophic hormone, GLP-2 (glucagons-like peptide 2), may be involved in the regulation of mesenteric blood flow. Changes in mesenteric blood flow...... were measured by Doppler ultrasound scanning of the superior mesenteric artery (SMA). The aim of the study was to demonstrate the influence of GLP-2 on this flow, expressed as changes in resistance index (RI). MATERIAL AND METHODS: A homogeneous group of 10 fasting healthy volunteers completed a 2-day...

  2. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

    Science.gov (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  3. DETECTING FOREST STRESS AND DECLINE IN RESPONSE TO INCREASING RIVER FLOW IN SOUTHWEST FLORIDA, USA

    Science.gov (United States)

    Forest stress and decline resulting from increased river flows were investigated in Myakka River State Park (MRSP), Florida, USA. Since 1977, land-use changes around the upper Myakka River watershed have resulted in significant increases in water entering the river, which have...

  4. Dietary rose hip exerts antiatherosclerotic effects and increases nitric oxide-mediated dilation in ApoE-null mice.

    Science.gov (United States)

    Cavalera, Michele; Axling, Ulrika; Rippe, Catarina; Swärd, Karl; Holm, Cecilia

    2017-06-01

    Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1β genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Age-dependent impact of CaV3.2 T-type calcium channel deletion on myogenic tone and flow-mediated vasodilatation in small arteries

    DEFF Research Database (Denmark)

    Mikkelsen, Miriam F.; Björling, Karl; Jensen, Lars Jørn

    2016-01-01

    , structural remodeling, and mRNA + protein expression in small mesenteric arteries from CaV3.2 knock-out vs. wild-type mice at young vs. mature adult age. In young mice, only, deletion of CaV3.2 led to enhanced myogenic response and ∼50 % reduction of flow-mediated vasodilatation. Ni(2+) had both CaV3...

  6. Activation of CFTR by ASBT-mediated bile salt absorption

    NARCIS (Netherlands)

    Bijvelds, MJC; Jorna, H; Verkade, HJ; Bot, AGM; Hofmann, F; Agellon, LB; Sinaasappel, M; de Jonge, HR

    2005-01-01

    In cholangiocytes, bile salt (BS) uptake via the apical sodium-dependent bile acid transporter (ASBT) may evoke ductular flow by enhancing cAMP-mediated signaling to the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. We considered that ASBT-mediated BS uptake in the distal

  7. The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

    Science.gov (United States)

    Khan, Sitara G; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R; Martin, Katherine; Khan, Faisal; O'Gallagher, Kevin; Chowienczyk, Philip J; Shah, Ajay M

    2017-09-01

    Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S -methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r 2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. Copyright © 2017 the American Physiological Society.

  8. Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice.

    Science.gov (United States)

    Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Sreedhar, Remya; Afrin, Rejina; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nomoto, Mayumi; Sone, Hirohito; Suzuki, Kenji; Watanabe, Kenichi

    2014-09-05

    BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Decreased retinal capillary flow is not a mediator of the protective myopia-diabetic retinopathy relationship.

    Science.gov (United States)

    Man, Ryan Eyn Kidd; Sasongko, Muhammad Bayu; Xie, Jing; Best, William J; Noonan, Jonathan E; Lo, Tiffany Ching Shen; Wang, Jie Jin; Luu, Chi D; Lamoureux, Ecosse L

    2014-09-30

    The mechanisms supporting the protective relationship between a longer axial length (AL) and a decreased risk of diabetic retinopathy (DR) remain unclear. Previous studies have demonstrated reduced retinal blood flow in axial myopia, and it has been suggested that the compromised retinal capillaries in diabetes are less likely to leak and rupture as a result of this decreased flow. In this study, we therefore investigated if reduced retinal capillary flow (RCF) is a potential mechanism underpinning this protective relationship. Retinal capillary flow was assessed using the Heidelberg Retinal Flowmeter in 150 eyes of 85 patients with diabetes aged 18+ years from the Royal Victorian Eye and Ear Hospital and St. Vincent's Hospital (Melbourne), Australia. Axial length was measured using the Intraocular Lens Master. Diabetic retinopathy was graded from two-field retinal photographs into none, mild, moderate, and severe DR using the modified Airlie House classification system. A total of 74 out of 150 eyes (49.3%) had DR. A longer AL was associated with decreased odds of DR presence (per mm increase in AL, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.41-0.91) and DR severity (OR: 0.65; 95% CI: 0.44-0.95). However, no association was found between AL and RCF (per mm increase in AL, regression coefficient [β] -1.80, 95% CI -13.50 to 9.50) or between RCF and DR (per unit increase in RCF, OR 1.00; 95% CI 0.99-1.00). Our finding suggests that diminished RCF may not be a major factor underlying the protective association between axial elongation and DR. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  10. Impaired Flow-Mediated Dilation Before, During and After Preeclampsia: A Systematic Review and Meta-analysis

    Science.gov (United States)

    Weissgerber, Tracey L.; Milic, Natasa M.; Milin-Lazovic, Jelena S.; Garovic, Vesna D.

    2015-01-01

    Endothelial dysfunction is believed to play a critical role in preeclampsia, however it is unclear whether this dysfunction precedes the pregnancy or is caused by early pathophysiological events. It is also unclear for how long vascular dysfunction may persist post-partum, and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia have worse vascular function compared to women who did not have preeclampsia by performing systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation (FMD). We included studies published before May 29, 2015 that examined FMD before, during and after preeclampsia. Differences in FMD between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE and Web of Science, 37 studies were eligible for the meta-analysis. When compared to women who did not have preeclampsia, women who had preeclampsia had lower FMD prior to the development of preeclampsia (~20–29 weeks gestation), at the time of preeclampsia, and for three years post-partum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with the increased risk for future cardiovascular disease. PMID:26711737

  11. Does Operational Risk Disclosure Quality Increase Operating Cash Flows?

    Directory of Open Access Journals (Sweden)

    Haitham Nobanee

    2017-12-01

    Full Text Available This study aims to measure the degree of operational risk disclosure and examine its impact on operating cash flow of banks listed on the UAE Abu Dhabi Stock Exchange (ADX and Dubai Financial Market (DFM during the period 2003-2016. The authors conducted content analysis of the annual reports to measure the degree of operational risk disclosure. In addition, they used dynamic panel data regressions to analyze the impact of operational risk disclosure on the operating cash flow generated by the banks. The results show a low degree of operational risk disclosure for all UAE banks, both Islamic and conventional. In addition, the results show no association between the levels of disclosure of operational risk and cash flow for all banks, conventional and Islamic. Operational risk disclosure of Islamic banks has not been examined by any prior researchers. In addition, this paper examines the potential impact of operational risk disclosure on the operating cash flow generated by the banks.

  12. Effects of shear flow on phase nucleation and crystallization.

    Science.gov (United States)

    Mura, Federica; Zaccone, Alessio

    2016-04-01

    Classical nucleation theory offers a good framework for understanding the common features of new phase formation processes in metastable homogeneous media at rest. However, nucleation processes in liquids are ubiquitously affected by hydrodynamic flow, and there is no satisfactory understanding of whether shear promotes or slows down the nucleation process. We developed a classical nucleation theory for sheared systems starting from the molecular level of the Becker-Doering master kinetic equation and we analytically derived a closed-form expression for the nucleation rate. The theory accounts for the effect of flow-mediated transport of molecules to the nucleus of the new phase, as well as for the mechanical deformation imparted to the nucleus by the flow field. The competition between flow-induced molecular transport, which accelerates nucleation, and flow-induced nucleus straining, which lowers the nucleation rate by increasing the nucleation energy barrier, gives rise to a marked nonmonotonic dependence of the nucleation rate on the shear rate. The theory predicts an optimal shear rate at which the nucleation rate is one order of magnitude larger than in the absence of flow.

  13. Accurate evaluation of viscoelasticity of radial artery wall during flow-mediated dilation in ultrasound measurement

    Science.gov (United States)

    Sakai, Yasumasa; Taki, Hirofumi; Kanai, Hiroshi

    2016-07-01

    In our previous study, the viscoelasticity of the radial artery wall was estimated to diagnose endothelial dysfunction using a high-frequency (22 MHz) ultrasound device. In the present study, we employed a commercial ultrasound device (7.5 MHz) and estimated the viscoelasticity using arterial pressure and diameter, both of which were measured at the same position. In a phantom experiment, the proposed method successfully estimated the elasticity and viscosity of the phantom with errors of 1.8 and 30.3%, respectively. In an in vivo measurement, the transient change in the viscoelasticity was measured for three healthy subjects during flow-mediated dilation (FMD). The proposed method revealed the softening of the arterial wall originating from the FMD reaction within 100 s after avascularization. These results indicate the high performance of the proposed method in evaluating vascular endothelial function just after avascularization, where the function is difficult to be estimated by a conventional FMD measurement.

  14. Magnon-mediated Dzyaloshinskii-Moriya torque in homogeneous ferromagnets

    KAUST Repository

    Manchon, Aurelien

    2014-12-01

    In thin magnetic layers with structural inversion asymmetry and spin-orbit coupling, the Dzyaloshinskii-Moriya interaction arises at the interface. When a spin-wave current jm flows in a system with a homogeneous magnetization m, this interaction produces an effective fieldlike torque of the form TFLm×(z×jm) as well as a dampinglike torque, TDLm×[(z×jm)×m], the latter only in the presence of spin-wave relaxation (z is normal to the interface). These torques mediated by the magnon flow can reorient the time-averaged magnetization direction and display a number of similarities with the torques arising from the electron flow in a magnetic two-dimensional electron gas with Rashba spin-orbit coupling. This magnon-mediated spin-orbit torque can be efficient in the case of magnons driven by a thermal gradient.

  15. Far-infrared radiation acutely increases nitric oxide production by increasing Ca2+ mobilization and Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

    International Nuclear Information System (INIS)

    Park, Jung-Hyun; Lee, Sangmi; Cho, Du-Hyong; Park, Young Mi; Kang, Duk-Hee; Jo, Inho

    2013-01-01

    Highlights: •Far-infrared (FIR) radiation increases eNOS-Ser 1179 phosphorylation and NO production in BAEC. •CaMKII and PKA mediate FIR-stimulated increases in eNOS-Ser 1179 phosphorylation. •FIR increases intracellular Ca 2+ levels. •Thermo-sensitive TRPV Ca 2+ channels are unlikely to be involved in the FIR-mediated eNOS-Ser 1179 phosphorylation pathway. -- Abstract: Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser 1179 ) in a time-dependent manner (up to 40 min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca 2+ levels. Treatment with KN-93, a selective inhibitor of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser 1179 phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser 1179 phosphorylation. This study suggests that FIR radiation increases NO

  16. Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

    Science.gov (United States)

    Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

    2001-01-01

    1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

  17. Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

    DEFF Research Database (Denmark)

    Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...... in cardiac output and was associated with the appearance of areas with myocardial necrosis in the regional left ventricular wall. The myocardial plasma flow rate and maximum plasma flow rate in response to a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease in the myocardial...... ng/kg for 60 min) on myocardial microvascular transport of a small hydrophilic indicator was examined by the single-injection, residue-detection method. Intracoronary infusion of rTNF-alpha increased myocardial microvascular transport after 120 min. This increase was preceded by a sustained decline...

  18. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.

    Science.gov (United States)

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-07-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Fluid-mediated stability and speed-increase for heaving hydrofoils swimming side-by-side

    Science.gov (United States)

    Newbolt, Joel; Zhang, Jun; Ristroph, Leif

    2017-11-01

    As an example of collective motion in active swimmers we study the fluid-mediated interaction between two heaving hydrofoils that swim with a fixed transverse separation (between the heaving mid-heights) but are free to independently choose their forward swimming speeds and positions. Experiments reveal that out-of-phase foils are attracted to a side-by-side configuration which also increases the swimming speed of the pair (up to 59% faster for our parameters), while in-phase foils are repelled from this configuration. Because this type of swimming is qualitatively similar to that of fish and birds this interaction could be important to schooling and flocking.

  20. Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps.

    Science.gov (United States)

    Schweizer, Dennis F; Schweizer, Riccardo; Zhang, Shengye; Kamat, Pranitha; Contaldo, Claudio; Rieben, Robert; Eberli, Daniel; Giovanoli, Pietro; Erni, Dominique; Plock, Jan A

    2013-10-01

    Botulinum toxin (BTX) A and B are commonly used for aesthetic indications and in neuromuscular disorders. New concepts seek to prove efficacy of BTX for critical tissue perfusion. Our aim was to evaluate BTX A and B in a mouse model of critical flap ischemia for preoperative and intraoperative application. BTX A and B were applied on the vascular pedicle of an axial pattern flap in mice preoperatively or intraoperatively. Blood flow, tissue oxygenation, tissue metabolism, flap necrosis rate, apoptosis assay, and RhoA and eNOS expression were endpoints. Blood-flow measurements 1 d after the flap operation revealed a significant reduction to 53% in the control group, while flow was maintained or increased in all BTX groups (103%-129%). Over 5 d all BTX groups showed significant increase in blood flow to 166-187% (P < 0.01). Microdialysis revealed an increase of glucose and reduced lactate/pyruvate ratio and glycerol levels in the flap tissue of all BTX groups. This resulted in significantly improved tissue survival in all BTX groups compared with the control group (62% ± 10%; all P < 0.01): BTX A preconditioning (84% ± 5%), BTX A application intraoperatively (88% ± 4%), BTX B preconditioning (91% ± 4%), and intraoperative BTX B treatment (92% ± 5%). This was confirmed by TUNEL assay. Immunofluorescence demonstrated RhoA and eNOS expression in BTX groups. All BTX applications were similarly effective, despite pharmacologic dissimilarities and different timing. In conclusion, we were able to show on a vascular, tissue, cell, and molecular level that BTX injection to the feeding arteries supports flap survival through ameliorated blood flow and oxygen delivery. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Mid-range adiabatic wireless energy transfer via a mediator coil

    International Nuclear Information System (INIS)

    Rangelov, A.A.; Vitanov, N.V.

    2012-01-01

    A technique for efficient mid-range wireless energy transfer between two coils via a mediator coil is proposed. By varying the coil frequencies, three resonances are created: emitter–mediator (EM), mediator–receiver (MR) and emitter–receiver (ER). If the frequency sweeps are adiabatic and such that the EM resonance precedes the MR resonance, the energy flows sequentially along the chain emitter–mediator–receiver. If the MR resonance precedes the EM resonance, then the energy flows directly from the emitter to the receiver via the ER resonance; then the losses from the mediator are suppressed. This technique is robust against noise, resonant constraints and external interferences. - Highlights: ► Efficient and robust mid-range wireless energy transfer via a mediator coil. ► The adiabatic energy transfer is analogous to adiabatic passage in quantum optics. ► Wireless energy transfer is insensitive to any resonant constraints. ► Wireless energy transfer is insensitive to noise in the neighborhood of the coils.

  2. The Impact of Increased Bladder Blood Flow on Storage Symptoms after Holmium Laser Enucleation of the Prostate.

    Directory of Open Access Journals (Sweden)

    Keisuke Saito

    Full Text Available In order to investigate how holmium laser enucleation of the prostate (HoLEP improves urinary storage symptoms, we assessed blood flow in the urinary bladder mucosa of patients with benign prostatic hyperplasia (BPH before and after laser surgery. Seventy-four consecutive patients with BPH (median age 69 years, range; 53-88 underwent HoLEP at our institution and are included in this study. We prospectively assessed the International Prostate Symptom Score (IPSS, IPSS-QOL Score, the Overactive Bladder Symptom Score (OABSS, uroflowmetry, and blood flow in the urinary bladder, before and after surgery. Blood flow in the bladder mucosa was measured using the OMEGA FLOW (OMEGAWAVE, Tokyo, Japan laser Doppler flowmeter. The median volume of the enucleated adenomas was 45.0 g (range: 25.0 to 83.2. The median IPSS improved significantly from 20 (range: 6-35 to 3 (0-22 (p < 0.001; Wilcoxon signed-rank test, as did the storage symptoms score, which decreased from 13 (2-20 to 3 (1-8 (p < 0.001. Median bladder blood flow increased at the trigone from 9.57 ± 0.83 ml/sec to 17.60 ± 1.08 ml/sec. Multiple regression analysis for the improved storage symptom score eliminated all explanatory variables except increased bladder perfusion. The data suggest that HoLEP improves blood flow in the bladder mucosa, which independently leads to the improvement of storage symptoms.

  3. The Impact of Increased Bladder Blood Flow on Storage Symptoms after Holmium Laser Enucleation of the Prostate

    Science.gov (United States)

    Ide, Hisamitsu; Aoki, Hiroaki; Muto, Satoru; Yamaguchi, Raizo; Tsujimura, Akira; Horie, Shigeo

    2015-01-01

    In order to investigate how holmium laser enucleation of the prostate (HoLEP) improves urinary storage symptoms, we assessed blood flow in the urinary bladder mucosa of patients with benign prostatic hyperplasia (BPH) before and after laser surgery. Seventy-four consecutive patients with BPH (median age 69 years, range; 53–88) underwent HoLEP at our institution and are included in this study. We prospectively assessed the International Prostate Symptom Score (IPSS), IPSS-QOL Score, the Overactive Bladder Symptom Score (OABSS), uroflowmetry, and blood flow in the urinary bladder, before and after surgery. Blood flow in the bladder mucosa was measured using the OMEGA FLOW (OMEGAWAVE, Tokyo, Japan) laser Doppler flowmeter. The median volume of the enucleated adenomas was 45.0 g (range: 25.0 to 83.2). The median IPSS improved significantly from 20 (range: 6–35) to 3 (0–22) (p<0.001; Wilcoxon signed-rank test), as did the storage symptoms score, which decreased from 13 (2–20) to 3 (1–8) (p<0.001). Median bladder blood flow increased at the trigone from 9.57±0.83 ml/sec to 17.60±1.08 ml/sec. Multiple regression analysis for the improved storage symptom score eliminated all explanatory variables except increased bladder perfusion. The data suggest that HoLEP improves blood flow in the bladder mucosa, which independently leads to the improvement of storage symptoms. PMID:26090819

  4. Flow and Reading Comprehension: Testing the Mediating Role of Emotioncy

    Science.gov (United States)

    Shahian, Leila; Pishghadam, Reza; Khajavy, Gholam Hassan

    2017-01-01

    Considering the importance of psychological factors in learners' reading abilities, this study examines the relationship between flow, emotioncy, and reading comprehension. To this end, 238 upper-intermediate and advanced English as a Foreign Language (EFL) learners were asked to take four tests of reading comprehension along with flow and…

  5. S phase entry of neural progenitor cells correlates with increased blood flow in the young subventricular zone.

    Directory of Open Access Journals (Sweden)

    Benjamin Lacar

    Full Text Available The postnatal subventricular zone (SVZ contains proliferating neural progenitor cells in close proximity to blood vessels. Insults and drug treatments acutely stimulate cell proliferation in the SVZ, which was assessed by labeling cells entering S phase. Although G1-to-S progression is metabolically demanding on a minute-to-hour time scale, it remains unknown whether increased SVZ cell proliferation is accompanied by a local hemodynamic response. This neurovascular coupling provides energy substrates to active neuronal assemblies. Transcardial dye perfusion revealed the presence of capillaries throughout the SVZ that constrict upon applications of the thromboxane A(2 receptor agonist U-46119 in acute brain slice preparations. We then monitored in vivo blood flow using laser Doppler flowmetry via a microprobe located either in the SVZ or a mature network. U-46119 injections into the lateral ventricle decreased blood flow in the SVZ and the striatum, which are near the ventricle. A 1-hour ventricular injection of epidermal and basic fibroblast growth factor (EGF and bFGF significantly increased the percentage of Sox2 transcription factor-positive cells in S phase 1.5 hours post-injection. This increase was accompanied by a sustained rise in blood flow in the SVZ but not in the striatum. Direct growth factor injections into the cortex did not alter local blood flow, ruling out direct effects on capillaries. These findings suggest that an acute increase in the number of G1-to-S cycling SVZ cells is accompanied by neurometabolic-vascular coupling, which may provide energy and nutrient for cell cycle progression.

  6. Profession of mediator as the professional provider of the mediation process

    Directory of Open Access Journals (Sweden)

    Jernej Šoštar

    2017-03-01

    Full Text Available The civil mediation programme, which is a court-connected programme, established as a form of alternative dispute resolution, is increasingly gaining ground as a field with its own theoretical and practical knowledge, principles and basic rules. Mediation has already set up its own body of knowledge, based on studies, classification of cases and the analyses of the results. In this article, we examine whether in the context of the development of mediation in Slovenia we might already talk about the profession of the mediator, defined as a provider of the mediation process. We examine the court-connected civil mediation and mediators who mediate at the court-connected civil mediation, and define them theoretically. By interviewing the mediation experts and mediators we examine their opinions about mediators and the court mediation. We examine the legal basis for the court-connected mediation programmes in Slovenia as well as in the European Union. Proceeding from our findings we conclude that the legal regulation of the court mediation in Slovenia is well established, and that the mediators of the court-connected civil mediation programmes can be accepted as the professional providers of the mediation process.

  7. Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

    Directory of Open Access Journals (Sweden)

    Sindy Giebe

    2017-08-01

    Full Text Available Tobacco smoking and hemodynamic forces are key stimuli in the development of endothelial dysfunction and atherosclerosis. High laminar flow has an atheroprotective effect on the endothelium and leads to a reduced response of endothelial cells to cardiovascular risk factors compared to regions with disturbed or low laminar flow. We hypothesize that the atheroprotective effect of high laminar flow could delay the development of endothelial dysfunction caused by cigarette smoking. Primary human endothelial cells were stimulated with increasing dosages of aqueous cigarette smoke extract (CSEaq. CSEaq reduced cell viability in a dose-dependent manner. The main mediator of cellular adaption to oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2 and its target genes heme oxygenase (decycling 1 (HMOX1 or NAD(PH quinone dehydrogenase 1 (NQO1 were strongly increased by CSEaq in a dose-dependent manner. High laminar flow induced elongation of endothelial cells in the direction of flow, activated the AKT/eNOS pathway, increased eNOS expression, phosphorylation and NO release. These increases were inhibited by CSEaq. Pro-inflammatory adhesion molecules intercellular adhesion molecule-1 (ICAM1, vascular cell adhesion molecule-1 (VCAM1, selectin E (SELE and chemokine (C-C motif ligand 2 (CCL2/MCP-1 were increased by CSEaq. Low laminar flow induced VCAM1 and SELE compared to high laminar flow. High laminar flow improved endothelial wound healing. This protective effect was inhibited by CSEaq in a dose-dependent manner through the AKT/eNOS pathway. Low as well as high laminar flow decreased adhesion of monocytes to endothelial cells. Whereas, monocyte adhesion was increased by CSEaq under low laminar flow, this was not evident under high laminar flow.This study shows the activation of major atherosclerotic key parameters by CSEaq. Within this process, high laminar flow is likely to reduce the harmful effects of CSEaq to a certain degree. The

  8. Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

    Science.gov (United States)

    Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

    2014-10-20

    Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

  9. Increased skills usage statistically mediates symptom reduction in self-guided internet-delivered cognitive-behavioural therapy for depression and anxiety: a randomised controlled trial.

    Science.gov (United States)

    Terides, Matthew D; Dear, Blake F; Fogliati, Vincent J; Gandy, Milena; Karin, Eyal; Jones, Michael P; Titov, Nickolai

    2018-01-01

    Cognitive-behavioural therapy (CBT) is an effective treatment for clinical and subclinical symptoms of depression and general anxiety, and increases life satisfaction. Patients' usage of CBT skills is a core aspect of treatment but there is insufficient empirical evidence suggesting that skills usage behaviours are a mechanism of clinical change. This study investigated if an internet-delivered CBT (iCBT) intervention increased the frequency of CBT skills usage behaviours and if this statistically mediated reductions in symptoms and increased life satisfaction. A two-group randomised controlled trial was conducted comparing internet-delivered CBT (n = 65) with a waitlist control group (n = 75). Participants were individuals experiencing clinically significant symptoms of depression or general anxiety. Mixed-linear models analyses revealed that the treatment group reported a significantly higher frequency of skills usage, lower symptoms, and higher life satisfaction by the end of treatment compared with the control group. Results from bootstrapping mediation analyses revealed that the increased skills usage behaviours statistically mediated symptom reductions and increased life satisfaction. Although skills usage and symptom outcomes were assessed concurrently, these findings support the notion that iCBT increases the frequency of skills usage behaviours and suggest that this may be an important mechanism of change.

  10. Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis.

    Directory of Open Access Journals (Sweden)

    G Hodge

    Full Text Available Bronchiectasis (BE in children is common in some communities including Indigenous children in Australia. Relatively little is known about the nature of systemic inflammation in these children, especially the contribution of specific pro-inflammatory and cytotoxic lymphocyte subsets: T-cells, natural killer (NK cells and NKT-like cells. We have shown that these cells produce increased cytotoxic (granzyme b and perforin and inflammatory (IFNγ and TNFα mediators in several adult chronic lung diseases and hypothesised that similar changes would be evident in children with BE.Intracellular cytotoxic mediators perforin and granzyme b and pro-inflammatory cytokines were measured in T cell subsets, NKT-like and NK cells from blood and bronchoalveolar samples from 12 children with BE and 10 aged-matched control children using flow cytometry.There was a significant increase in the percentage of CD8+ T cells and T and NKT-like subsets expressing perforin/granzyme and IFNγ and TNFα in blood in BE compared with controls. There was a further increase in the percentage of pro-inflammatory cytotoxic T cells in Indigenous compared with non-Indigenous children. There was no change in any of these mediators in BAL.Childhood bronchiectasis is associated with increased systemic pro-inflammatory/cytotoxic lymphocytes in the peripheral blood. Future studies need to examine the extent to which elevated levels of pro-inflammatory cytotoxic cells predict future co-morbidities.

  11. The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

    Science.gov (United States)

    Khan, Sitara G.; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R.; Martin, Katherine; Khan, Faisal; O’Gallagher, Kevin; Chowienczyk, Philip J.

    2017-01-01

    Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. PMID:28646032

  12. Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; di Giosia, Paolo; Barnabei, Remo; Allegaert, Leen; Bernaert, Herwig; Ferri, Claudio

    2015-02-01

    Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P cocoa flavonoids per day increased FMD (P Cocoa dose-dependently decreased PWV (P Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ± 1.03  mmHg, P cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

  13. Far-infrared radiation acutely increases nitric oxide production by increasing Ca{sup 2+} mobilization and Ca{sup 2+}/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung-Hyun; Lee, Sangmi [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Cho, Du-Hyong [Department of Neuroscience, School of Medicine, Konkuk University, Seoul 143-701 (Korea, Republic of); Park, Young Mi [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Kang, Duk-Hee [Division of Nephrology, Department of Internal Medicine, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Jo, Inho, E-mail: inhojo@ewha.ac.kr [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of)

    2013-07-12

    Highlights: •Far-infrared (FIR) radiation increases eNOS-Ser{sup 1179} phosphorylation and NO production in BAEC. •CaMKII and PKA mediate FIR-stimulated increases in eNOS-Ser{sup 1179} phosphorylation. •FIR increases intracellular Ca{sup 2+} levels. •Thermo-sensitive TRPV Ca{sup 2+} channels are unlikely to be involved in the FIR-mediated eNOS-Ser{sup 1179} phosphorylation pathway. -- Abstract: Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser{sup 1179}) in a time-dependent manner (up to 40 min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca{sup 2+} levels. Treatment with KN-93, a selective inhibitor of Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. This

  14. Peak expiratory flow mediates the relationship between handgrip strength and timed up and go performance in elderly women, but not men.

    Science.gov (United States)

    Ritti-Dias, Raphael Mendes; Cucato, Gabriel Grizzo; de Mello Franco, Fábio Gazelato; Cendoroglo, Maysa Seabra; Nasri, Fábio; Monteiro-Costa, Maria Luiza; de Carvalho, José Antonio Maluf; de Matos, Luciana Diniz Nagem Janot

    2016-09-01

    The aim of the present study was to verify if there is sex difference in the associations among handgrip strength, peak expiratory flow (PEF) and timed up and go (TUG) test results. The sample included 288 consecutive elderly men (n=93) and women (n=195). Functional capacity was measured using the TUG test, and muscle strength was measured based on handgrip. Moreover, as a measure of current health status, PEF was evaluated. Linear regression procedures were performed to analyze the relationships between handgrip and both PEF and TUG test results, with adjustment for confounders, and to identify the possible mediating role of PEF in the association between handgrip strength and TUG test results. In men, handgrip strength was associated with both PEF and TUG performance (prelationship between handgrip strength and TUG performance remained significant. In women, handgrip strength was also associated with both PEF and TUG performance (prelationship between handgrip strength and TUG performance was no longer significant. Mobility in the elderly is sex dependent. In particular, PEF mediates the relationship between handgrip strength and TUG performance in women, but not in men.

  15. Camphor induces cold and warm sensations with increases in skin and muscle blood flow in human.

    Science.gov (United States)

    Kotaka, Tomohiko; Kimura, Shoji; Kashiwayanagi, Makoto; Iwamoto, Jun

    2014-01-01

    Application of camphor to the skin has been empirically thought to improve blood circulation. However, camphor's effects on blood circulation to the skin and on thermal sensation have not been well elucidated. In this study, we examined its effects on the quality of sensation as well as on skin and muscle blood flow in human. Nine adults (average age 37±9.4 years) participated in the study. Petroleum jelly containing 5%, 10%, 20% camphor, or 2% menthol was separately applied to the skin on the medial side of one forearm of each subject. Just after the application, camphor at each concentration induced a cold sensation in a dose-dependent manner. Within 10 min, each subject reported that the cold sensation had faded, after which it was replaced by a warm sensation. As reported previously, a cold sensation was induced by application of 2% menthol, but the subjects did not adapt to that sensation. In addition, menthol did not induce a warm sensation at all. Application of menthol has been shown to increase blood flow in the skin. Finally, we measured blood flow in skin and muscle after the application of camphor or menthol. Application of camphor or menthol separately induced increases in local blood flow in the skin and muscle. The present results indicate that camphor induces both cold and warm sensations and improves blood circulation.

  16. MC EMiNEM maps the interaction landscape of the Mediator.

    Directory of Open Access Journals (Sweden)

    Theresa Niederberger

    Full Text Available The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs, a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC sampling with an Expectation-Maximization (EM algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

  17. MC EMiNEM maps the interaction landscape of the Mediator.

    Science.gov (United States)

    Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C; Martin, Dietmar E; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

    2012-01-01

    The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

  18. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    Science.gov (United States)

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

    2016-01-01

    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

  19. Pollen-Mediated Gene Flow in Maize: Implications for Isolation Requirements and Coexistence in Mexico, the Center of Origin of Maize.

    Science.gov (United States)

    Baltazar, Baltazar M; Castro Espinoza, Luciano; Espinoza Banda, Armando; de la Fuente Martínez, Juan Manuel; Garzón Tiznado, José Antonio; González García, Juvencio; Gutiérrez, Marco Antonio; Guzmán Rodríguez, José Luis; Heredia Díaz, Oscar; Horak, Michael J; Madueño Martínez, Jesús Ignacio; Schapaugh, Adam W; Stojšin, Duška; Uribe Montes, Hugo Raúl; Zavala García, Francisco

    2015-01-01

    Mexico, the center of origin of maize (Zea mays L.), has taken actions to preserve the identity and diversity of maize landraces and wild relatives. Historically, spatial isolation has been used in seed production to maintain seed purity. Spatial isolation can also be a key component for a strategy to minimize pollen-mediated gene flow in Mexico between transgenic maize and sexually compatible plants of maize conventional hybrids, landraces, and wild relatives. The objective of this research was to generate field maize-to-maize outcrossing data to help guide coexistence discussions in Mexico. In this study, outcrossing rates were determined and modeled from eight locations in six northern states, which represent the most economically important areas for the cultivation of hybrid maize in Mexico. At each site, pollen source plots were planted with a yellow-kernel maize hybrid and surrounded by plots with a white-kernel conventional maize hybrid (pollen recipient) of the same maturity. Outcrossing rates were then quantified by assessing the number of yellow kernels harvested from white-kernel hybrid plots. The highest outcrossing values were observed near the pollen source (12.9% at 1 m distance). The outcrossing levels declined sharply to 4.6, 2.7, 1.4, 1.0, 0.9, 0.5, and 0.5% as the distance from the pollen source increased to 2, 4, 8, 12, 16, 20, and 25 m, respectively. At distances beyond 20 m outcrossing values at all locations were below 1%. These trends are consistent with studies conducted in other world regions. The results suggest that coexistence measures that have been implemented in other geographies, such as spatial isolation, would be successful in Mexico to minimize transgenic maize pollen flow to conventional maize hybrids, landraces and wild relatives.

  20. Microvascular function in pre-eclampsia is influenced by insulin resistance and an imbalance of angiogenic mediators.

    Science.gov (United States)

    Ghosh, Anshuman; Freestone, Nicholas S; Anim-Nyame, Nicholas; Arrigoni, Francesca I F

    2017-04-01

    In preeclampsia, maternal microvascular function is disrupted and angiogenesis is dysfunctional. Insulin resistance that occurs in some pregnancies also pathologically affects microvascular function. We wished to examine the relationship of angiogenic mediators and insulin resistance on microvascular health in pregnancy. We performed a nested, case-control study of 16 women who developed preeclampsia with 17 normal pregnant controls. We hypothesized that the impaired microvascular blood flow in preeclamptic women associated with an increased ratio of the antiangiogenic factors; (s-endoglin [sEng] and soluble fms-like tyrosine kinase-1 [sFlt-1]) and proangiogenic molecule (placental growth factor [PlGF]) could be influenced by insulin resistance. Serum samples taken after 28 weeks of gestation were measured for the angiogenic factors, insulin, and glucose alongside the inflammatory marker; tumor necrosis factor-α and endothelial activation, namely; soluble vascular cell adhesion molecule 1, intercellular adhesion molecule-1, and e-selectin. Maternal microvascular blood flow, measured by strain gauge plethysmography, correlated with ratios of pro- and antiangiogenic mediators independently of preeclampsia. Decreased microvascular function measured in preeclampsia strongly correlated with both the antiangiogenic factor (sFlt-1 + sEng): PlGF ratio and high levels of insulin resistance, and combining insulin resistance with antiangiogenic factor ratios further strengthened this relationship. In pregnancy, microvascular blood flow is strongly associated with perturbations in pro- and antiangiogenic mediators. In preeclampsia, the relationship of maternal microvascular dysfunction with antiangiogenic mediators is strengthened when combined with insulin resistance. © 2017 Kingston University. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  1. FLOW MEDIATED DILATION AND CAROTID INTIMA MEDIA THICKNESS IN PATIENTS WITH CHRONIC GASTRITIS ASSOCIATED WITH HELICOBACTER PYLORI INFECTION.

    Science.gov (United States)

    Judaki, Arezo; Norozi, Siros; Ahmadi, Mohammad Reza Hafezi; Ghavam, Samira Mis; Asadollahi, Khairollah; Rahmani, Asghar

    2017-12-01

    Endothelial dysfunction is one of the early stages of vascular diseases. The aim of this study was to investigate the endothelial dysfunction markers in patients with chronic gastritis associated with Helicobacter pylori (H. pylori) infection. By a cross sectional study, basic and clinical information of 120 participants (40 patients with positive H. pylori infection, 40 patients with negative H. pylori infection and 40 healthy people) were analyzed. Carotid intima media thickness and flow-mediated dilation levels were measured in all patients and controls. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured with Elisa for all subjects. IgG level was assessed in chronic gastritis patients. The flow-mediated dilation level in patients with positive H. pylori infection (0.17%±0.09) was significantly lower than those with negative H. pylori infection (0.21% ±0.10, Pgastritis. The levels of flow-mediated dilation, carotid intima media thickness and sICAM-1 were higher among patients with positive H. pylori infection. Patients with chronic gastritis associated with H. pylori infection are at risk of endothelial dysfunction due to flow-mediated dilation and carotid intima media thickness abnormalities and increased level of sICAM-1 and sVCAM-1.

  2. Measurement of regional pulmonary blood volume in patients with increased pulmonary blood flow or pulmonary arterial hypertension

    International Nuclear Information System (INIS)

    Wollmer, P.; Rozcovek, A.; Rhodes, C.G.; Allan, R.M.; Maseri, A.

    1984-01-01

    The effects of chronic increase in pulmonary blood flow and chronic pulmonary hypertension on regional pulmonary blood volume was measured in two groups of patients. One group of patients had intracardiac, left-to-right shunts without appreciable pulmonary hypertension, and the other consisted of patients with Eisenmenger's syndrome or primary pulmonary hypertension, i.e. patients with normal or reduced blood flow and severe pulmonary hypertension. A technique based on positron tomography was used to measure lung density (by transmission scanning) and regional pulmonary blood volume (after inhalation of /sup 11/CO). The distribution of pulmonary blood volume was more uniform in patients with chronic increase in pulmonary blood flow than in normal subjects. There were also indications of an absolute increase in intrapulmonary blood volume by about 15%. In patients with chronic pulmonary arterial hypertension, the distribution of pulmonary blood volume was also abnormally uniform. There was, however, no indication that overall intrapulmonary blood volume was substantially different from normal subjects. The abnormally uniform distribution of pulmonary blood volume can be explained by recruitment and/or dilatation of vascular beds. Intrapulmonary blood volume appears to be increased in patients with intracardiac, left-to-right shunts. With the development of pulmonary hypertension, intrapulmonary blood volume falls, which may be explained by reactive changes in the vasculature and/or obliteration of capillaries

  3. Bioelectrochemical ethanol production through mediated acetate reduction by mixed cultures.

    Science.gov (United States)

    Steinbusch, Kirsten J J; Hamelers, Hubertus V M; Schaap, Joris D; Kampman, Christel; Buisman, Cees J N

    2010-01-01

    Biological acetate reduction with hydrogen is a potential method to convert wet biomass waste into ethanol. Since the ethanol concentration and reaction rates are low, this research studies the feasibility of using an electrode, in stead of hydrogen, as an electron donor for biological acetate reduction in conjunction of an electron mediator. Initially, the effect of three selected mediators on metabolic flows during acetate reduction with hydrogen was explored; subsequently, the best performing mediator was used in a bioelectrochemical system to stimulate acetate reduction at the cathode with mixed cultures at an applied cathode potential of -550 mV. In the batch test, methyl viologen (MV) was found to accelerate ethanol production 6-fold and increased ethanol concentration 2-fold to 13.5 +/- 0.7 mM compared to the control. Additionally, MV inhibited n-butyrate and methane formation, resulting in high ethanol production efficiency (74.6 +/- 6%). In the bioelectrochemical system, MV addition to an inoculated cathode led directly to ethanol production (1.82 mM). Hydrogen was coproduced at the cathode (0.0035 Nm(3) hydrogen m(-2) d(-1)), so it remained unclear whether acetate was reduced to ethanol by electrons supplied by the mediator or by hydrogen. As MV reacted irreversibly at the cathode, ethanol production stopped after 5 days.

  4. PROGRESSIVE MUSCLE RELAXATION INCREASE PEAK EXPIRATORY FLOW RATE ON CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS

    Directory of Open Access Journals (Sweden)

    Tintin Sukartini

    2017-07-01

    Full Text Available Introduction: Limited progressive air flow in Chronic Obstructive Pulmonary Disease (COPD can caused by small airway disease (bronchiolitis obstructive and loss of elasticity of the lung (emphysema. Further it can be decreasing the quality of life in COPD patients because dyspnea and uncomfortable in activity. Progressive muscle relaxation (PMR is one of the relaxation technique that can repair pulmonary ventilation by decreasing chronic constriction of the respiratory muscles. The objective of this study was to analyze the effect of progressive muscle relaxation on raised peak expiratory flow rate (PEFR. Method: A pre-experimental one group pre-post test design was used in this study. Population was all of the COPD patients at Pulmonary Specialist Polyclinic Dr Mohamad Soewandhie Surabaya. There were 8 respondents taken by using purposive sampling. PEFR was counted by using peak flow meter every six day. Data were analyzed by using Paired t-Test with significance level  p≤0.05. Result: The result showed that PMR had significance level on increasing of PEFR (p=0.012. Discussion: It can be concluded that PMR has an effect on raise PEFR. Further studies are recommended to measure the effect of PMR on respiratory rate (RR, heart rate (HR subjective dyspnoe symptoms, forced expiration volume on the first minute (FEV1 and mid maximum flow rate (MMFR in COPD patients.

  5. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture

    DEFF Research Database (Denmark)

    Benrick, Anna; Kokosar, Milana; Hu, Min

    2017-01-01

    was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS...... of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.-Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M......., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener-Victorin, E. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture....

  6. Dynamical Messengers for Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Anson; Torroba, Gonzalo; /SLAC /Stanford U., Phys. Dept.

    2011-08-17

    We construct models of indirect gauge mediation where the dynamics responsible for breaking supersymmetry simultaneously generates a weakly coupled subsector of messengers. This provides a microscopic realization of messenger gauge mediation where the messenger and hidden sector fields are unified into a single sector. The UV theory is SQCD with massless and massive quarks plus singlets, and at low energies it flows to a weakly coupled quiver gauge theory. One node provides the primary source of supersymmetry breaking, which is then transmitted to the node giving rise to the messenger fields. These models break R-symmetry spontaneously, produce realistic gaugino and sfermion masses, and give a heavy gravitino.

  7. Nurses' exhaustion: the role of flow at work between job demands and job resources.

    Science.gov (United States)

    Zito, Margherita; Cortese, Claudio G; Colombo, Lara

    2016-01-01

    In the light of the job demands-resources model, this study aimed to detect the mediating role of flow at work between job demands and job resources on one side, and exhaustion on the other. In a historical period where it is necessary to reduce the abandonment of nursing profession, flow is a useful tool to investigate the factors that can promote work motivation and prevent psychological distress. A cross-sectional study was conducted in a hospital, and 279 nurses completed a questionnaire. Analyses conducted are descriptive statistics, alphas, correlations and a structural equations model that considers the mediating role of flow at work. Findings show both the central role of job resources in determining flow at work, and the mediating role of flow at work in decreasing exhaustion, starting from job resources, and in decreasing the effect of job demands on exhaustion. Moreover, flow at work directly decreases exhaustion. Results show the relevance of containing job demands and provide job resources to promote positive experiences at work. To promote flow at work, organizations should offer specific resources, such as supervisors' support, job autonomy, and psychological support to manage the emotional charge. © 2015 John Wiley & Sons Ltd.

  8. Modelling food-web mediated effects of hydrological variability and environmental flows.

    Science.gov (United States)

    Robson, Barbara J; Lester, Rebecca E; Baldwin, Darren S; Bond, Nicholas R; Drouart, Romain; Rolls, Robert J; Ryder, Darren S; Thompson, Ross M

    2017-11-01

    Environmental flows are designed to enhance aquatic ecosystems through a variety of mechanisms; however, to date most attention has been paid to the effects on habitat quality and life-history triggers, especially for fish and vegetation. The effects of environmental flows on food webs have so far received little attention, despite food-web thinking being fundamental to understanding of river ecosystems. Understanding environmental flows in a food-web context can help scientists and policy-makers better understand and manage outcomes of flow alteration and restoration. In this paper, we consider mechanisms by which flow variability can influence and alter food webs, and place these within a conceptual and numerical modelling framework. We also review the strengths and weaknesses of various approaches to modelling the effects of hydrological management on food webs. Although classic bioenergetic models such as Ecopath with Ecosim capture many of the key features required, other approaches, such as biogeochemical ecosystem modelling, end-to-end modelling, population dynamic models, individual-based models, graph theory models, and stock assessment models are also relevant. In many cases, a combination of approaches will be useful. We identify current challenges and new directions in modelling food-web responses to hydrological variability and environmental flow management. These include better integration of food-web and hydraulic models, taking physiologically-based approaches to food quality effects, and better representation of variations in space and time that may create ecosystem control points. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  9. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1

    DEFF Research Database (Denmark)

    Guan, Xinfu; Stoll, Barbara; Lu, Xiaofeng

    2003-01-01

    (n = 8) received consecutive intravenous infusions of saline, GLP-2, and GLP-2 plus N(G)-Nitro-L-arginine methyl ester (L-NAME, 50 micromol x kg(-1) x hour(-1)) for 4 hours each. RESULTS: GLP-2 acutely increased portal-drained visceral (PDV) blood flow rate (+25%) and intestinal blood volume (+51......%) in TPN-fed piglets. GLP-2 also increased intestinal constitutive nitric oxide synthase (NOS) activity and endothelial NOS protein abundance. GLP-2 acutely increased PDV glucose uptake (+90%) and net lactate production (+79%). Co-infusion of GLP-2 plus L-NAME did not increase either PDV blood flow rate......, and this response is nitric oxide-dependent. These findings suggest that GLP-2 may play an important physiological role in the regulation of intestinal blood flow and that nitric oxide is involved in GLP-2 receptor function....

  10. Low level of pollen-mediated gene flow from cultivated to wild grapevine: consequences for the evolution of the endangered subspecies Vitis vinifera L. subsp. silvestris.

    Science.gov (United States)

    Di Vecchi-Staraz, Manuel; Laucou, Valérie; Bruno, Gérard; Lacombe, Thierry; Gerber, Sophie; Bourse, Thibaut; Boselli, Maurizio; This, Patrice

    2009-01-01

    A parentage and a paternity-based approach were tested for estimation of pollen-mediated gene flow in wild grapevine (Vitis vinifera L. subsp. silvestris), a wind-pollinated species occurring in Mediterranean Europe and southwestern Asia. For this purpose, 305 seedlings collected in 2 years at 2 locations in France from 4 wild female individuals and 417 wild individuals prospected from France and Italy were analyzed using 20 highly polymorphic microsatellite loci. Their profiles were compared with a database consisting of 3203 accessions from the Institut National de la Recherche Agronomique Vassal collection including cultivars, rootstocks, interspecific hybrids, and other wild individuals. Paternity was assigned for 202 (66.2%) of the 305 seedlings, confirming the feasibility of the method. Most of the fertilizing pollen could be assigned to wild males growing nearby. Estimates of pollen immigration from the cultivated compartment (i.e., the totality of cultivars) ranged from 4.2% to 26% from nearby vineyards and from hidden pollinators such as cultivars and rootstocks that had escaped from farms. In an open landscape, the pollen flow was correlated to the distance between individuals, the main pollinator being the closest wild male (accounting for 51.4-86.2% of the pollen flow). In a closed landscape, more complex pollination occurred. Analysis of the parentage of the 417 wild individuals also revealed relationships between nearby wild individuals, but in the case of 12 individuals (3%), analysis revealed pollen immigration from vineyards, confirming the fitness of the hybrid seedlings. These pollen fluxes may have a significant effect on the evolution of wild populations: on the one hand, the low level of pollen-mediated gene flow from cultivated to wild grapevine could contribute to a risk of extinction of the wild compartment (i.e., the totality of the wild individuals). On the other hand, pollen dispersal within the wild populations may induce inbreeding

  11. Epoetin beta pegol ameliorates flow-mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats.

    Science.gov (United States)

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Kawasaki, Ryohei; Endo, Koichi; Shimonaka, Yasushi; Hirata, Michinori

    2017-04-01

    Patients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.R.A.) is a drug for the treatment of renal anemia. In this study, we investigated the effect of C.E.R.A. on vascular endothelial function as evaluated by flow-mediated dilation (FMD) and the relationship between hematopoiesis and FMD in diabetic nephropathy rats. Male Spontaneously Diabetic Torii rats (SDT, 22 weeks old) were used. C.E.R.A. (0.6, 1.2 μg/kg) was administered subcutaneously once every 2 weeks for 8 weeks. At 1 week after last administration (31 weeks old), we assessed FMD in the femoral arteries of anesthetized rats using a high-resolution ultrasound system. FMD was also measured 1 week after single C.E.R.A. treatment (5.0 μg/kg) to examine the influence of hematopoiesis. Flow-mediated dilation was significantly decreased in SDT rats before the start of C.E.R.A. treatment (22 weeks old). Repeated administration of C.E.R.A. dose-dependently improved FMD in SDT rats (31 weeks old) without changing blood glucose, nitroglycerin-induced vasodilation, or kidney function. Long-term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of SDT rats, which showed a positive correlation with FMD. On the other hand, there was no correlation between FMD and Hb or Hct in SDT rats. Furthermore, at 1 week after single administration of C.E.R.A., FMD was not significantly improved although hemoglobin levels were comparable with levels following long-term C.E.R.A. Long-term treatment with C.E.R.A. improved FMD in SDT rats even after onset of endothelial dysfunction. © 2017 The Authors. Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

  12. Kindlin-3 Is Essential for the Resting α4β1 Integrin-mediated Firm Cell Adhesion under Shear Flow Conditions.

    Science.gov (United States)

    Lu, Ling; Lin, ChangDong; Yan, ZhanJun; Wang, Shu; Zhang, YouHua; Wang, ShiHui; Wang, JunLei; Liu, Cui; Chen, JianFeng

    2016-05-06

    Integrin-mediated rolling and firm cell adhesion are two critical steps in leukocyte trafficking. Integrin α4β1 mediates a mixture of rolling and firm cell adhesion on vascular cell adhesion molecule-1 (VCAM-1) when in its resting state but only supports firm cell adhesion upon activation. The transition from rolling to firm cell adhesion is controlled by integrin activation. Kindlin-3 has been shown to bind to integrin β tails and trigger integrin activation via inside-out signaling. However, the role of kindlin-3 in regulating resting α4β1-mediated cell adhesion is not well characterized. Herein we demonstrate that kindlin-3 was required for the resting α4β1-mediated firm cell adhesion but not rolling adhesion. Knockdown of kindlin-3 significantly decreased the binding of kindlin-3 to β1 and down-regulated the binding affinity of the resting α4β1 to soluble VCAM-1. Notably, it converted the resting α4β1-mediated firm cell adhesion to rolling adhesion on VCAM-1 substrates, increased cell rolling velocity, and impaired the stability of cell adhesion. By contrast, firm cell adhesion mediated by Mn(2+)-activated α4β1 was barely affected by knockdown of kindlin-3. Structurally, lack of kindlin-3 led to a more bent conformation of the resting α4β1. Thus, kindlin-3 plays an important role in maintaining a proper conformation of the resting α4β1 to mediate both rolling and firm cell adhesion. Defective kindlin-3 binding to the resting α4β1 leads to a transition from firm to rolling cell adhesion on VCAM-1, implying its potential role in regulating the transition between integrin-mediated rolling and firm cell adhesion. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Kindlin-3 Is Essential for the Resting α4β1 Integrin-mediated Firm Cell Adhesion under Shear Flow Conditions*

    Science.gov (United States)

    Lu, Ling; Lin, ChangDong; Yan, ZhanJun; Wang, Shu; Zhang, YouHua; Wang, ShiHui; Wang, JunLei; Liu, Cui; Chen, JianFeng

    2016-01-01

    Integrin-mediated rolling and firm cell adhesion are two critical steps in leukocyte trafficking. Integrin α4β1 mediates a mixture of rolling and firm cell adhesion on vascular cell adhesion molecule-1 (VCAM-1) when in its resting state but only supports firm cell adhesion upon activation. The transition from rolling to firm cell adhesion is controlled by integrin activation. Kindlin-3 has been shown to bind to integrin β tails and trigger integrin activation via inside-out signaling. However, the role of kindlin-3 in regulating resting α4β1-mediated cell adhesion is not well characterized. Herein we demonstrate that kindlin-3 was required for the resting α4β1-mediated firm cell adhesion but not rolling adhesion. Knockdown of kindlin-3 significantly decreased the binding of kindlin-3 to β1 and down-regulated the binding affinity of the resting α4β1 to soluble VCAM-1. Notably, it converted the resting α4β1-mediated firm cell adhesion to rolling adhesion on VCAM-1 substrates, increased cell rolling velocity, and impaired the stability of cell adhesion. By contrast, firm cell adhesion mediated by Mn2+-activated α4β1 was barely affected by knockdown of kindlin-3. Structurally, lack of kindlin-3 led to a more bent conformation of the resting α4β1. Thus, kindlin-3 plays an important role in maintaining a proper conformation of the resting α4β1 to mediate both rolling and firm cell adhesion. Defective kindlin-3 binding to the resting α4β1 leads to a transition from firm to rolling cell adhesion on VCAM-1, implying its potential role in regulating the transition between integrin-mediated rolling and firm cell adhesion. PMID:26994136

  14. Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP.

    Science.gov (United States)

    Tsai, Shang-Ru; Yin, Rui; Huang, Ying-Ying; Sheu, Bor-Ching; Lee, Si-Chen; Hamblin, Michael R

    2015-03-01

    Low-level light therapy (LLLT) is used to stimulate healing, reduce pain and inflammation, and preserve tissue from dying. LLLT has been shown to protect cells in culture from dying after various cytotoxic insults, and LLLT is known to increase the cellular ATP content. Previous studies have demonstrated that maintaining a sufficiently high ATP level is necessary for the efficient induction and execution of apoptosis steps after photodynamic therapy (PDT). We asked whether LLLT would protect cells from cytotoxicity due to PDT, or conversely whether LLLT would enhance the efficacy of PDT mediated by mono-l-aspartyl chlorin(e6) (NPe6). Increased ATP could lead to enhanced cell uptake of NPe6 by the energy dependent process of endocytosis, and also to more efficient apoptosis. In this study, human osteosarcoma cell line MG-63 was subjected to 1.5J/cm(2) of 810nm near infrared radiation (NIR) followed by addition of 10μM NPe6 and after 2h incubation by 1.5J/cm(2) of 652nm red light for PDT. PDT combined with LLLT led to higher cell death and increased intracellular reactive oxygen species compared to PDT alone. The uptake of NPe6 was moderately increased by LLLT, and cellular ATP was increased. The mitochondrial respiratory chain inhibitor antimycin A abrogated the LLLT-induced increase in cytotoxicity. Taken together, these results demonstrate that LLLT potentiates NPe6-mediated PDT via increased ATP synthesis and is a potentially promising strategy that could be applied in clinical PDT. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Increased drop formation frequency via reduction of surfactant interactions in flow-focusing microfluidic devices.

    Science.gov (United States)

    Josephides, Dimitris N; Sajjadi, Shahriar

    2015-01-27

    Glass capillary based microfluidic devices are able to create extremely uniform droplets, when formed under the dripping regime, at low setup costs due to their ease of manufacture. However, as they are rarely parallelized, simple methods to increase droplet production from a single device are sought. Surfactants used to stabilize drops in such systems often limit the maximum flow rate that highly uniform drops can be produced due to the lowering interfacial tension causing jetting. In this paper we show that by simple design changes we can limit the interactions of surfactants and maximize uniform droplet production. Three flow-focused configurations are explored: a standard glass capillary device (consisting of a single round capillary inserted into a square capillary), a nozzle fed device, and a surfactant shielding device (both consisting of two round capillaries inserted into either end of a square capillary). In principle, the maximum productivity of uniform droplets is achieved if surfactants are not present. It was found that surfactants in the standard device greatly inhibit droplet production by means of interfacial tension lowering and tip-streaming phenomena. In the nozzle fed configuration, surfactant interactions were greatly limited, yielding flow rates comparable to, but lower than, a surfactant-free system. In the surfactant shielding configuration, flow rates were equal to that of a surfactant-free system and could make uniform droplets at rates an order of magnitude above the standard surfactant system.

  16. Brain blood flow and blood pressure during hypoxia in the epaulette shark Hemiscyllium ocellatum, a hypoxia-tolerant elasmobranch.

    Science.gov (United States)

    Söderström, V; Renshaw, G M; Nilsson, G E

    1999-04-01

    The key to surviving hypoxia is to protect the brain from energy depletion. The epaulette shark (Hemiscyllium ocellatum) is an elasmobranch able to resist energy depletion and to survive hypoxia. Using epi-illumination microscopy in vivo to observe cerebral blood flow velocity on the brain surface, we show that cerebral blood flow in the epaulette shark is unaffected by 2 h of severe hypoxia (0.35 mg O2 l-1 in the respiratory water, 24 C). Thus, the epaulette shark differs from other hypoxia- and anoxia-tolerant species studied: there is no adenosine-mediated increase in cerebral blood flow such as that occurring in freshwater turtles and cyprinid fish. However, blood pressure showed a 50 % decrease in the epaulette shark during hypoxia, indicating that a compensatory cerebral vasodilatation occurs to maintain cerebral blood flow. We observed an increase in cerebral blood flow velocity when superfusing the normoxic brain with adenosine (making sharks the oldest vertebrate group in which this mechanism has been found). The adenosine-induced increase in cerebral blood flow velocity was reduced by the adenosine receptor antagonist aminophylline. Aminophylline had no effect upon the maintenance of cerebral blood flow during hypoxia, however, indicating that adenosine is not involved in maintaining cerebral blood flow in the epaulette shark during hypoxic hypotension.

  17. Effect of Exercise Intervention on Flow-Mediated Dilation in Overweight and Obese Adults: Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Younsun Son

    2017-01-01

    Full Text Available The objective of this meta-analysis is to summarize the effect of exercise intervention on flow-mediated dilatation (FMD in overweight and obese adults. We searched four electronic databases (PubMed/Medline, Scopus, and CINAHL through June 2016 for relevant studies pertaining to the effectiveness of exercise intervention on FMD. Seventeen of the 91 studies identified met the inclusion criteria. Comprehensive Meta-Analysis software (version 3 was used to compute the standardized mean difference effect size (ES and 95% CI using a random effects model. We calculated 34 ESs. We found that exercise intervention had medium and positive effects on FMD, with an overall ES of 0.522 (95% CI = 0.257, 0.786. Heterogeneity of ESs was observed (Qb=239, p≤0.001, I2 = 86.19, and the effect was moderated by comorbidity (Qb = 6.39, df = 1, p=0.011. A large ES for the combination exercise, low intensity exercise, and comorbidity subgroups (ES = 0.82~1.24 was found. We conclude that while exercise intervention significantly improves FMD in overweight and obese adults, the effect may depend on the different characteristics of exercise intervention and on participants’ demographics.

  18. Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation.

    Science.gov (United States)

    Weitlauf, Carl; Ward, Nicholas J; Lambert, Wendi S; Sidorova, Tatiana N; Ho, Karen W; Sappington, Rebecca M; Calkins, David J

    2014-11-12

    Progression of neurodegeneration in disease and injury is influenced by the response of individual neurons to stressful stimuli and whether this response includes mechanisms to counter declining function. Transient receptor potential (TRP) cation channels transduce a variety of disease-relevant stimuli and can mediate diverse stress-dependent changes in physiology, both presynaptic and postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates degeneration of retinal ganglion cell neurons and their axons with elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell survival in mouse models of glaucoma. We found that induced elevations of ocular pressure increased TRPV1 in ganglion cells and its colocalization at excitatory synapses to their dendrites, whereas chronic elevation progressively increased ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was transient and supported a reversal of the effect of TRPV1 on ganglion cells from hyperpolarizing to depolarizing, which was also transient. Short-term enhancement of TRPV1-mediated activity led to a delayed increase in axonal spontaneous excitation that was absent in ganglion cells from Trpv1(-/-) retina. In isolated ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes along ganglion cell dendrites that corresponded to sites of elevated Ca(2+). These results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress. Copyright © 2014 the authors 0270-6474/14/3415369-13$15.00/0.

  19. Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Demas, Gregory E; Polacek, Kelly M; Durazzo, Alfredo; Jasnow, Aaron M

    2004-12-01

    Among the suite of seasonal adaptations displayed by nontropical rodents, some species demonstrate increased territorial aggression in short compared with long day lengths despite basal levels of testosterone. The precise physiological mechanisms mediating seasonal changes in aggression, however, remain largely unknown. The goal of the present study was to examine the role of melatonin, as well as adrenal hormones, in the regulation of seasonal aggression in male Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2 h before lights out for 10 consecutive days. In Experiment 2, hamsters received adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received adrenalectomies (ADx); control animals in both experiments received sham surgeries. Animals in both experiments subsequently received daily injections of melatonin or vehicle as in Experiment 1. Animals in all experiments were tested using a resident-intruder model of aggression. In Experiment 1, exogenous melatonin treatment increased aggression compared with control hamsters. In Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment 3, the melatonin-induced increase in aggression was significantly attenuated by ADx. Collectively, the results of the present study demonstrate that short day-like patterns of melatonin increase aggression in male Siberian hamsters and suggest that increased aggression is due, in part, to changes in adrenocortical steroids.

  20. Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits.

    Science.gov (United States)

    Li, Bao; Tian, Jing; Sun, Yi; Xu, Tao-Rui; Chi, Rui-Fang; Zhang, Xiao-Li; Hu, Xin-Ling; Zhang, Yue-An; Qin, Fu-Zhong; Zhang, Wei-Fang

    2015-05-01

    Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase activity and endoplasmic reticulum (ER) stress are increased after myocardial infarction (MI). In this study, we proposed to test whether activation of the NADPH oxidase in the remote non-infarcted myocardium mediates ER stress and left ventricular (LV) remodeling after MI. Rabbits with MI or sham operation were randomly assigned to orally receive an NADPH oxidase inhibitor apocynin or placebo for 30 days. The agents were administered beginning at 1 week after surgery. MI rabbits exhibited decreases in LV fractional shortening, LV ejection fraction and the first derivative of the LV pressure rise, which were abolished by apocynin treatment. NADPH oxidase Nox2 protein and mRNA expressions were increased in the remote non-infarcted myocardium after MI. Immunolabeling further revealed that Nox2 was increased in cardiac myocytes in the remote myocardium. The apocynin treatment prevented increases in the Nox2 expression, NADPH oxidase activity, oxidative stress, myocyte apoptosis and GRP78, CHOP and cleaved caspase 12 protein expression in the remote myocardium. The apocynin treatment also attenuated increases in myocyte diameter and cardiac fibrosis. In cultured H9C2 cardiomyocytes exposed to angiotensin II, an important stimulus for post-MI remodeling, Nox2 knockdown with siRNA significantly inhibited angiotensin II-induced NADPH oxidase activation, reactive oxygen species and GRP78 and CHOP protein expression. We conclude that NADPH oxidase inhibition attenuates increased ER stress in the remote non-infarcted myocardium and LV remodeling late after MI in rabbits. These findings suggest that the activation of NADPH oxidase in the remote non-infarcted myocardium mediates increased ER stress, contributing to myocyte apoptosis and LV remodeling after MI. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26

    International Nuclear Information System (INIS)

    Cutler, Murray J.; Lowthers, Erica L.; Richard, Cynthia L.; Hajducek, Dagmar M.; Spagnuolo, Paul A.; Blay, Jonathan

    2015-01-01

    Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12. We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays. 5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations. Our results indicate that conventional anticancer agents may act to inhibit chemokine-mediated migration through eradication of CXCR4+ cells and attenuation of

  2. Magnon-mediated Dzyaloshinskii-Moriya torque in homogeneous ferromagnets

    KAUST Repository

    Manchon, Aurelien; Ndiaye, Papa Birame; Moon, Jung-Hwan; Lee, Hyun-Woo; Lee, Kyung-Jin

    2014-01-01

    the time-averaged magnetization direction and display a number of similarities with the torques arising from the electron flow in a magnetic two-dimensional electron gas with Rashba spin-orbit coupling. This magnon-mediated spin-orbit torque can

  3. Pollen-Mediated Movement of Herbicide Resistance Genes in Lolium rigidum.

    Directory of Open Access Journals (Sweden)

    Iñigo Loureiro

    Full Text Available The transfer of herbicide resistance genes by pollen is a major concern in cross-pollinated species such as annual ryegrass (Lolium rigidum. A two-year study was conducted in the greenhouse, under favorable conditions for pollination, to generate information on potential maximum cross-pollination. This maximum cross-pollination rate was 56.1%. A three-year field trial was also conducted to study the cross-pollination rates in terms of distance and orientation to an herbicide-resistant pollen source. Under field conditions, cross-pollination rates varied from 5.5% to 11.6% in plants adjacent to the pollen source and decreased with increasing distances (1.5 to 8.9% at 15 m distance and up to 4.1% at 25 m in the downwind direction. Environmental conditions influenced the cross-pollination both under greenhouse and field conditions. Data were fit to an exponential decay model to predict gene flow at increasing distances. This model predicted an average gene flow of 7.1% when the pollen donor and recipient plants were at 0 m distance from each other. Pollen-mediated gene flow declined by 50% at 16.7 m from the pollen source, yet under downwind conditions gene flow of 5.2% was predicted at 25 m, the farthest distance studied. Knowledge of cross-pollination rates will be useful for assessing the spread of herbicide resistance genes in L. rigidum and in developing appropriate strategies for its mitigation.

  4. Data on a single oral dose of camu camu (Myrciaria dubia pericarp extract on flow-mediated vasodilation and blood pressure in young adult humans

    Directory of Open Access Journals (Sweden)

    Tadayoshi Miyashita

    2018-02-01

    Full Text Available This data article describes the flow-mediated vasodilation (FMD responses, represented by changes in arterial diameter, and blood pressure changes in young adults after a single oral dose of camu camu (Myrciaria dubia pericarp extract or placebo (cross-over design. Ten healthy men and 10 healthy women participated in this study. Ultrasonic diagnostic equipment was used to monitor arterial diameter changes, indicative of FMD, for 110 s after the administration of the camu camu extract or placebo. In addition, the systolic and diastolic blood pressure values were recorded.

  5. Data on a single oral dose of camu camu (Myrciaria dubia) pericarp extract on flow-mediated vasodilation and blood pressure in young adult humans.

    Science.gov (United States)

    Miyashita, Tadayoshi; Koizumi, Ryosuke; Myoda, Takao; Sagane, Yoshimasa; Niwa, Koichi; Watanabe, Toshihiro; Minami, Kazuhiro

    2018-02-01

    This data article describes the flow-mediated vasodilation (FMD) responses, represented by changes in arterial diameter, and blood pressure changes in young adults after a single oral dose of camu camu ( Myrciaria dubia ) pericarp extract or placebo (cross-over design). Ten healthy men and 10 healthy women participated in this study. Ultrasonic diagnostic equipment was used to monitor arterial diameter changes, indicative of FMD, for 110 s after the administration of the camu camu extract or placebo. In addition, the systolic and diastolic blood pressure values were recorded.

  6. Assessment of Equine Autoimmune Thrombocytopenia (EAT by flow cytometry

    Directory of Open Access Journals (Sweden)

    Schwarzwald Colin

    2001-04-01

    Full Text Available Abstract Rationale Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i decreased production; ii increased utilization; iii increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT; or iv platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. Objectives This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. Findings The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i increased number of platelets with high FSC and high SSC, ii a significant number of those gigantic platelets had strong fluorescent signal (IgG bound, iii very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. Conclusions This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses.

  7. Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia.

    Science.gov (United States)

    Farrag, Mohamed; Drobish, Julie K; Puhl, Henry L; Kim, Joyce S; Herold, Paul B; Kaufman, Marc P; Ruiz-Velasco, Victor

    2017-12-01

    Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed

  8. Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Sardar Sindhu

    2018-01-01

    Full Text Available Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC, or primary monocytes were treated with hydrogen peroxide (H2O2 for induction of reactive oxygen species (ROS-mediated oxidative stress. Superoxide dismutase (SOD activity was measured using a commercial kit. Data (mean±SEM were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI. ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB/mitogen activated protein kinase (MAPK signaling as well as endoplasmic reticulum (ER stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress

  9. Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress.

    Science.gov (United States)

    Sindhu, Sardar; Akhter, Nadeem; Kochumon, Shihab; Thomas, Reeby; Wilson, Ajit; Shenouda, Steve; Tuomilehto, Jaakko; Ahmad, Rasheed

    2018-01-01

    Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H2O2) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student's t-test and Pobesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation. © 2018 The Author(s). Published by S. Karger AG, Basel.

  10. Mediating social media use : connecting parents mediation strategies and social media literacy

    OpenAIRE

    Daneels, Rowan; Vanwynsberghe, Hadewijch

    2017-01-01

    Abstract: Increasingly complex and multipurpose social media platforms require digital competences from parents and adolescents alike. While adolescents grow up with social media, parents have more difficulties with them, leading to uncertainties regarding their adolescents social media mediation. This study contributes to parental mediation research by (1) investigating whether mediation strategies defined by previous research are also relevant for social media use, and (2) exploring whether...

  11. Altered whole kidney blood flow autoregulation in a mouse model of reduced beta-ENaC.

    Science.gov (United States)

    Grifoni, Samira C; Chiposi, Rumbidzayi; McKey, Susan E; Ryan, Michael J; Drummond, Heather A

    2010-02-01

    Renal blood flow (RBF) autoregulation is mediated by at least two mechanisms, the fast acting myogenic response (approximately 5 s) and slow acting tubuloglomerular feedback (TGF; approximately 25 s). Previous studies suggest epithelial Na(+) channel (ENaC) family proteins, beta-ENaC in particular, mediate myogenic constriction in isolated renal interlobar arteries. However, it is unknown whether beta-ENaC-mediated myogenic constriction contributes to RBF autoregulation in vivo. Therefore, the goal of this investigation was to determine whether the myogenic mediated RBF autoregulation is inhibited in a mouse model of reduced beta-ENaC (m/m). To address this goal, we evaluated the temporal response of RBF and renal vascular resistance (RVR) to a 2-min step increase in mean arterial pressure (MAP). Pressure-induced changes in RBF and RVR at 0-5, 6-25, and 110-120 s after step increase in MAP were used to assess the contribution of myogenic and TGF mechanisms and steady-state autoregulation, respectively. The rate of the initial increase in RVR, attributed to the myogenic mechanism, was reduced by approximately 50% in m/m mice, indicating the speed of the myogenic response was inhibited. Steady-state autoregulation was similar between beta-ENaC +/+ and m/m mice. Although the rate of the secondary increase in RVR, attributed to TGF, was similar in beta-ENaC +/+ and m/m mice, however, it occurred over a longer period (+10 s), which may have allowed TGF to compensate for a loss in myogenic autoregulation. Our findings suggest beta-ENaC is an important mediator of renal myogenic constriction-mediated RBF autoregulation in vivo.

  12. Altered whole kidney blood flow autoregulation in a mouse model of reduced β-ENaC

    Science.gov (United States)

    Grifoni, Samira C.; Chiposi, Rumbidzayi; McKey, Susan E.; Ryan, Michael J.

    2010-01-01

    Renal blood flow (RBF) autoregulation is mediated by at least two mechanisms, the fast acting myogenic response (∼5 s) and slow acting tubuloglomerular feedback (TGF; ∼25 s). Previous studies suggest epithelial Na+ channel (ENaC) family proteins, β-ENaC in particular, mediate myogenic constriction in isolated renal interlobar arteries. However, it is unknown whether β-ENaC-mediated myogenic constriction contributes to RBF autoregulation in vivo. Therefore, the goal of this investigation was to determine whether the myogenic mediated RBF autoregulation is inhibited in a mouse model of reduced β-ENaC (m/m). To address this goal, we evaluated the temporal response of RBF and renal vascular resistance (RVR) to a 2-min step increase in mean arterial pressure (MAP). Pressure-induced changes in RBF and RVR at 0–5, 6–25, and 110–120 s after step increase in MAP were used to assess the contribution of myogenic and TGF mechanisms and steady-state autoregulation, respectively. The rate of the initial increase in RVR, attributed to the myogenic mechanism, was reduced by ∼50% in m/m mice, indicating the speed of the myogenic response was inhibited. Steady-state autoregulation was similar between β-ENaC +/+ and m/m mice. Although the rate of the secondary increase in RVR, attributed to TGF, was similar in β-ENaC +/+ and m/m mice, however, it occurred over a longer period (+10 s), which may have allowed TGF to compensate for a loss in myogenic autoregulation. Our findings suggest β-ENaC is an important mediator of renal myogenic constriction-mediated RBF autoregulation in vivo. PMID:19889952

  13. Increased expression of matrix metalloproteinase-1 in systemic vessels of preeclamptic women: a critical mediator of vascular dysfunction.

    Science.gov (United States)

    Estrada-Gutierrez, Guadalupe; Cappello, Renato E; Mishra, Nikita; Romero, Roberto; Strauss, Jerome F; Walsh, Scott W

    2011-01-01

    This study was conducted to determine the following: (1) whether matrix metalloproteinase-1 (MMP-1) is increased in systemic vessels of preeclamptic women, (2) whether this increase might be mediated by neutrophils, and (3) whether MMP-1 could be responsible for vascular dysfunction. Omental arteries and plasma were collected from healthy pregnant and preeclamptic women. Omental arteries were evaluated for gene and protein expression of MMP-1, collagen type 1α, tissue inhibitor of metalloproteinase-1, and vascular reactivity to MMP-1. Gene and protein expression levels were also evaluated in human vascular smooth muscle cells (VSMCs) co-cultured with activated neutrophils, reactive oxygen species, or tumor necrosis factor α. Vessel expression of MMP-1 and circulating MMP-1 levels were increased in preeclamptic women, whereas vascular expression of collagen or tissue inhibitor of metalloproteinase-1 were down-regulated or unchanged. In cultured VSMCs, the imbalance in collagen-regulating genes of preeclamptic vessels was reproduced by treatment with neutrophils, tumor necrosis factor α, or reactive oxygen species. Chemotaxis studies with cultured cells revealed that MMP-1 promoted recruitment of neutrophils via vascular smooth muscle release of interleukin-8. Furthermore, MMP-1 induced vasoconstriction via protease-activated receptor-1, whose expression was significantly increased in omental arteries of preeclamptic women and in VSMCs co-cultured with neutrophils. Collectively, these findings disclose a novel role for MMP-1 as a mediator of vasoconstriction and vascular dysfunction in preeclampsia. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21WAF1/CIP1

    International Nuclear Information System (INIS)

    Kim, Mi Jin; Yoo, Young A.; Kim, Hyung Jung; Kang, Seongman; Kim, Yong Geon; Kim, Jun Suk; Yoo, Young Do

    2005-01-01

    Ribosomal proteins not only act as components of the translation apparatus but also regulate cell proliferation and apoptosis. A previous study reported that MRPL41 plays an important role in p53-dependent apoptosis. It also showed that MRPL41 arrests the cell cycle by stabilizing p27 Kip1 in the absence of p53. This study found that MRPL41 mediates the p21 WAF1/CIP1 -mediated G1 arrest in response to serum starvation. The cells were released from serum starvation-induced G1 arrest via the siRNA-mediated blocking of MRPL41 expression. Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21 WAF1/CIP1 and p27 Kip1 levels under the growth inhibitory conditions

  15. Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, Henning; Gemmer, Carsten

    2002-01-01

    The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow......, respectively (P exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction....... was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release...

  16. Flow and heat transfer in laminar–turbulent transitional flow regime under rolling motion

    International Nuclear Information System (INIS)

    Yuan, Hongsheng; Tan, Sichao; Zhuang, Nailiang; Lan, Shu

    2016-01-01

    Highlights: • Flow and heat transfer experiment in transitional flow regime under rolling motion. • Increases of average friction factor and Nu were found. • Periodic breakdown of laminar flow contributes to the increase. • Nonlinear variation of pressure drop or Nu with Re also contributes to the increase. • Effect of critical Reynolds number shift was discussed. - Abstract: Flow and heat transfer characteristics under rolling motion are extremely important to thermohydraulic analysis of offshore nuclear reactors. An experimental study was conducted in a heated rectangular channel to investigate flow and heat transfer in laminar–turbulent transitional flow regime under rolling motion. The results showed that the average friction factor and Nusselt number are higher than that of the corresponding steady flow as the flow rate fluctuates in transitional flow regime. Larger relative flow rate fluctuation was observed under larger rolling amplitude or higher rolling frequency. In the same manner, larger increases of average friction factor and Nusselt number were achieved under larger rolling amplitude or higher rolling frequency. The increases were mainly caused by the flow rate fluctuation through periodic breakdown of laminar flow and development of turbulence in laminar–turbulent transitional flow regime. First, turbulence, which enhances the rate of momentum and energy exchange, occurs near the crest of flow rate wave even the flow is still in laminar flow regime according to the average Reynolds number. Second, as a result of rapid increases of the friction and heat transfer with Reynolds number in transitional flow regime, the increases of the friction and the heat transfer near the crest of flow rate wave are larger than the decreases of them near the trough of flow rate wave, which also contributes to increases of average friction and heat transfer. Additionally, the effect of critical Reynolds number shift under unsteady flow and heating

  17. Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function.

    Science.gov (United States)

    Mannaerts, Dominique; Faes, Ellen; Goovaerts, Inge; Stoop, Tibor; Cornette, Jerome; Gyselaers, Wilfried; Spaanderman, Marc; Van Craenenbroeck, Emeline M; Jacquemyn, Yves

    2017-11-01

    Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy ( P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy ( P function, obtained by FMD, is deteriorated in PE versus normal pregnancy ( P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy ( P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy. Copyright © 2017 the American Physiological Society.

  18. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  19. Omalizumab Increases the Intrinsic Sensitivity of Human Basophils to IgE-Mediated Stimulation

    Science.gov (United States)

    MacGlashan, Donald; Saini, Sarbjit S.

    2013-01-01

    Background Treatment of allergic patients with omalizumab results in a paradoxical increase in their basophil histamine release response, ex vivo, to crosslinking anti-IgE antibody. It is not known whether this change in response is associated with an increase in intrinsic cellular sensitivity, which would be a paradoxical response. Objective To determine if the increase in response to anti-IgE Ab is a reflection of an increased cellular sensitivity, expressed as molecules of antigen-specific IgE per basophil required to produce a 50% of maximal response. Methods Patients were treated with omalizumab or placebo agent for 12 weeks (NCT01003301 at ClinicalTrials.gov) and the metric of basophil sensitivity was assessed at 4 time points, baseline, 6–8 weeks, 12 weeks (after which treatment stopped) and 24 weeks (12 weeks after the end of treatment). Results As observed previously, treatment with omalizumab resulted in a marked increase in the maximal histamine release induced by crosslinking anti-IgE Ab. This change was accompanied by a marked shift in intrinsic basophil sensitivity, ranging from 2.5 to 125 fold, with an average of 6 fold at the midpoint of the treatment to 12 fold after 12 weeks. The magnitude of the increase in cellular sensitivity was inversely related to the starting sensitivity or the starting maximum histamine release. The increased cellular sensitivity also occurred when using LTC4 secretion as a metric of the basophil response. 12 weeks after the end of treatment, cellular sensitivity was found to shift towards the baseline level although the return to baseline was not yet complete at this time point. Conclusions Treatment with omalizumab results in a markedly increased sensitivity of basophils to IgE-mediated stimulation, in terms of the number of IgE molecules required to produce a given response. These results provide a better quantitative sense of the phenotypic change that occurs in basophils during omalizumab treatment which has

  20. Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling.

    Science.gov (United States)

    Bretón-Romero, Rosa; Feng, Bihua; Holbrook, Monika; Farb, Melissa G; Fetterman, Jessica L; Linder, Erika A; Berk, Brittany D; Masaki, Nobuyuki; Weisbrod, Robert M; Inagaki, Elica; Gokce, Noyan; Fuster, Jose J; Walsh, Kenneth; Hamburg, Naomi M

    2016-03-01

    Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus. © 2016 American Heart

  1. The study on flow characteristics of butterfly valve using flow visualization

    International Nuclear Information System (INIS)

    Yang, S. M.; Hong, S. D.; Song, D. S.; Park, J. K.; Park, J. I.; Shin, S. K.; Kim, H. J.

    2005-01-01

    Flow visualization of butterfly valve is tested for four types(15 deg., 30 .deg., 45 .deg., and 90 .deg.) of valve opening angle. The inner flow characteristics of valve are studied. The flow variation was measured using a high speed camera which takes 500 frames per second with 1024 x 1024 pixels. These captured images were used for calculation to analyze two dimensional flow velocity of the valve. The smaller opening angle, the more increasing the differential pressure of a butterfly valve. Therefore, we know that the complex flow is occurred by increasing the differential pressure. And it is found that the flowing backward is more increased according to the increase of the opening angle of a butterfly valve. However, its flow pattern is similar to a simple pipe flow when the opening angle is 90 .deg.

  2. Tyrosine kinase inhibitors as modulators of trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity in breast cancer cell lines.

    Science.gov (United States)

    Collins, Denis M; Gately, Kathy; Hughes, Clare; Edwards, Connla; Davies, Anthony; Madden, Stephen F; O'Byrne, Kenneth J; O'Donovan, Norma; Crown, John

    2017-09-01

    Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab. Using LDH-release assays, we investigated the impact of antigen modulation, assay duration and peripheral blood mononuclear cell (PBMC) activity on trastuzumab-mediated ADCC in breast cancer models of maximal (SKBR3) and minimal (MCF-7) target antigen expression to determine if modulating the ADCC response to trastuzumab using TKIs may be a viable approach for enhancing tumor immune reactivity. HER2 levels were determined in lapatinib, afatinib and neratinib-treated SKBR3 and MCF-7 using high content analysis (HCA). Trastuzumab-mediated ADCC was assessed following treatment with TKIs utilising a colorimetric LDH release-based protocol at 4 and 12h timepoints. PBMC activity was assessed against non-MHC-restricted K562 cells. A flow cytometry-based method (CFSE/7-AAD) was also used to measure trastuzumab-mediated ADCC in medium-treated SKBR3 and MCF-7. HER2 antigen levels were significantly altered by the three TKIs in both cell line models. The TKIs significantly reduced LDH levels directly in SKBR3 cells but not MCF-7. Lapatinib and neratinib augment trastuzumab-related ADCC in SKBR3 but the effect was not consistent with antigen expression levels and was dependent on volunteer PBMC activity (vs. K562). A 12h assay timepoint produced more consistent results. Trastuzumab-mediated ADCC (PBMC:target cell ratio of 10:1) was measured at 7.6±4.7% (T12) by LDH assay and 19±3.2 % (T12) using the flow cytometry-based method in the antigen-low model MCF-7. In the presence of effector cells with high

  3. Alpha adrenergic receptor blockade increases capillarisation and fractional O2 extraction and lowers blood flow in contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Mortensen, Stefan P; Egginton, Stuart; Madsen, Mads

    2017-01-01

    AIM: To investigate the effect of elevated basal shear stress on angiogenesis in humans, and the role of enhanced skeletal muscle capillarisation on blood flow and O2 extraction. METHODS: Limb haemodynamics and O2 extraction was measured at rest and during one-leg knee-extensor exercise (12 and 24W......) in 10 healthy untrained young men before and after 4 weeks treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day(-1) ). Corresponding biopsies were taken from the m. vastus lateralis. RESULTS: Resting leg blood flow was increased by 57% 6 hours following Terazosin treatment (P... basal capillary-to-fibre ratio was 1.69±0.08 and increased to 1.90±0.08 after treatment (Pblood flow and venous lactate levels lower (6-7%; P

  4. Empirical study on flow experience in China tourism e-commerce market

    Directory of Open Access Journals (Sweden)

    Jianling Wang

    2015-04-01

    Full Text Available Purpose: While tourism e-commerce develops rapidly in China, these channels are truly new to both web providers and web consumers, understanding the nature of these media attaches greater importance. This study investigates the mediation effects of flow experience on the relationship between motivation and behavior intention in tourism e-commerce.Design/methodology/approach: Based on the technology acceptance model, an empirical study is designed to test this relationship.we estimated the measurement model with 13 manifest indicators and 4 latent constructs by CFA to assess the reliability and validity of the construct measures, then tested hypotheses by OLS regression and a formal three-step mediation procedure.Findings: Overall, the results reveal that trust is incorporated in motivation and play it’s role together with other motivations; telepresence and concentration are confirmed in flow experience, and both partially mediated the relationship.Research limitations/implications: This study demonstrates that to improve consumers’ usage adoption, marketers should pay much attention to not only consumers’ motivation but also the areas such as flow experience.Originality/value: This study takes flow experience as a new perspective to explore china tourism e-commerce, estimates its measurement and tests its roles between motivation and behavior intention.

  5. Development of multiplex loop mediated isothermal amplification (m-LAMP) label-based gold nanoparticles lateral flow dipstick biosensor for detection of pathogenic Leptospira

    International Nuclear Information System (INIS)

    Nurul Najian, A.B.; Engku Nur Syafirah, E.A.R.; Ismail, Nabilah; Mohamed, Maizan; Yean, Chan Yean

    2016-01-01

    In recent years extensive numbers of molecular diagnostic methods have been developed to meet the need of point-of-care devices. Efforts have been made towards producing rapid, simple and inexpensive DNA tests, especially in the diagnostics field. We report on the development of a label-based lateral flow dipstick for the rapid and simple detection of multiplex loop-mediated isothermal amplification (m-LAMP) amplicons. A label-based m-LAMP lateral flow dipstick assay was developed for the simultaneous detection of target DNA template and a LAMP internal control. This biosensor operates through a label based system, in which probe-hybridization and the additional incubation step are eliminated. We demonstrated this m-LAMP assay by detecting pathogenic Leptospira, which causes the re-emerging disease Leptospirosis. The lateral flow dipstick was developed to detect of three targets, the LAMP target amplicon, the LAMP internal control amplicon and a chromatography control. Three lines appeared on the dipstick, indicating positive results for all representative pathogenic Leptospira species, whereas two lines appeared, indicating negative results, for other bacterial species. The specificity of this biosensor assay was 100% when it was tested with 13 representative pathogenic Leptospira species, 2 intermediate Leptospira species, 1 non-pathogenic Leptospira species and 28 other bacteria species. This study found that this DNA biosensor was able to detect DNA at concentrations as low as 3.95 × 10 −1 genomic equivalent ml −1 . An integrated m-LAMP and label-based lateral flow dipstick was successfully developed, promising simple and rapid visual detection in clinical diagnostics and serving as a point-of-care device. - Highlights: • We develop multiplex LAMP label-based lateral flow dipstick biosensor for detection of pathogenic Leptospira. • We design primers for multiplex LAMP targeting the conserved LipL32 gene of pathogenic Leptospira and LAMP internal

  6. Development of multiplex loop mediated isothermal amplification (m-LAMP) label-based gold nanoparticles lateral flow dipstick biosensor for detection of pathogenic Leptospira

    Energy Technology Data Exchange (ETDEWEB)

    Nurul Najian, A.B.; Engku Nur Syafirah, E.A.R.; Ismail, Nabilah [Department of Medical Microbiology & Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia); Mohamed, Maizan [Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, City Campus, Pengkalan Chepa, Locked Bag 36, 16100 Kota Bharu, Kelantan (Malaysia); Yean, Chan Yean, E-mail: yeancyn@yahoo.com [Department of Medical Microbiology & Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia); Institute for Research in Molecular Medicine (INFORMM), Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia)

    2016-01-15

    In recent years extensive numbers of molecular diagnostic methods have been developed to meet the need of point-of-care devices. Efforts have been made towards producing rapid, simple and inexpensive DNA tests, especially in the diagnostics field. We report on the development of a label-based lateral flow dipstick for the rapid and simple detection of multiplex loop-mediated isothermal amplification (m-LAMP) amplicons. A label-based m-LAMP lateral flow dipstick assay was developed for the simultaneous detection of target DNA template and a LAMP internal control. This biosensor operates through a label based system, in which probe-hybridization and the additional incubation step are eliminated. We demonstrated this m-LAMP assay by detecting pathogenic Leptospira, which causes the re-emerging disease Leptospirosis. The lateral flow dipstick was developed to detect of three targets, the LAMP target amplicon, the LAMP internal control amplicon and a chromatography control. Three lines appeared on the dipstick, indicating positive results for all representative pathogenic Leptospira species, whereas two lines appeared, indicating negative results, for other bacterial species. The specificity of this biosensor assay was 100% when it was tested with 13 representative pathogenic Leptospira species, 2 intermediate Leptospira species, 1 non-pathogenic Leptospira species and 28 other bacteria species. This study found that this DNA biosensor was able to detect DNA at concentrations as low as 3.95 × 10{sup −1} genomic equivalent ml{sup −1}. An integrated m-LAMP and label-based lateral flow dipstick was successfully developed, promising simple and rapid visual detection in clinical diagnostics and serving as a point-of-care device. - Highlights: • We develop multiplex LAMP label-based lateral flow dipstick biosensor for detection of pathogenic Leptospira. • We design primers for multiplex LAMP targeting the conserved LipL32 gene of pathogenic Leptospira and LAMP

  7. Dissolved organic matter composition of winter flow in the Yukon River basin: Implications of permafrost thaw and increased groundwater discharge

    Science.gov (United States)

    O'Donnell, Jonathan A.; Aiken, George R.; Walvoord, Michelle Ann; Butler, Kenna D.

    2012-01-01

    Groundwater discharge to rivers has increased in recent decades across the circumpolar region and has been attributed to thawing permafrost in arctic and subarctic watersheds. Permafrost-driven changes in groundwater discharge will alter the flux of dissolved organic carbon (DOC) in rivers, yet little is known about the chemical composition and reactivity of dissolved organic matter (DOM) of groundwater in permafrost settings. Here, we characterize DOM composition of winter flow in 60 rivers and streams of the Yukon River basin to evaluate the biogeochemical consequences of enhanced groundwater discharge associated with permafrost thaw. DOC concentration of winter flow averaged 3.9 ± 0.5 mg C L−1, yet was highly variable across basins (ranging from 20 mg C L−1). In comparison to the summer-autumn period, DOM composition of winter flow had lower aromaticity (as indicated by specific ultraviolet absorbance at 254 nm, or SUVA254), lower hydrophobic acid content, and a higher proportion of hydrophilic compounds (HPI). Fluorescence spectroscopy and parallel factor analysis indicated enrichment of protein-like fluorophores in some, but not all, winter flow samples. The ratio of DOC to dissolved organic nitrogen, an indicator of DOM biodegradability, was positively correlated with SUVA254 and negatively correlated with the percentage of protein-like compounds. Using a simple two-pool mixing model, we evaluate possible changes in DOM during the summer-autumn period across a range of conditions reflecting possible increases in groundwater discharge. Across three watersheds, we consistently observed decreases in DOC concentration and SUVA254 and increases in HPI with increasing groundwater discharge. Spatial patterns in DOM composition of winter flow appear to reflect differences in the relative contributions of groundwater from suprapermafrost and subpermafrost aquifers across watersheds. Our findings call for more explicit consideration of DOC loss and stabilization

  8. Reduced blood flow increases the in vivo ammonium ion concentration in the RIF-1 tumor

    International Nuclear Information System (INIS)

    Constantinidis, Ioannis; Gamcsik, Michael P.

    1995-01-01

    Purpose: Previous studies from our laboratory have suggested that pooling of ammonium in tumor tissues may be caused by its inefficient removal due to the poor vasculature commonly found in tumors. The purpose of these experiments was to validate the relationship between tumor ammonium ion concentration and tumor blood flow, and to determine whether large concentrations of ammonium ion detected by Nuclear Magnetic Resonance (NMR) spectroscopy are either produced within the tumor or simply imported into the tumor through the blood stream. Methods and Materials: To test this hypothesis, we reduced blood flow in subcutaneously grown Radiation Induced Fibrosarcoma-1 (RIF-1) tumors, either by creating partial ischemia with a bolus injection of hydralazine or by occlusion with surgical sutures. 14 N and 31 P NMR spectroscopy were used to detect the presence of ammonium, and to assess the bioenergetic status of the tumors, respectively. Results: A correlation between ammonium ion concentration and (PCr(P i )) ratio was established for untreated tumors. An increase in the in vivo tumor ammonium ion concentration was observed for every tumor that experienced a reduction in blood flow caused by either hydralazine injection or suture ligation. Changes in ammonium ion concentration paralleled changes in the bioenergetics of hydralazine-treated tumors. Conclusion: Our results support the hypothesis that a reduction in tumor blood flow is responsible for the accumulation of ammonium in tumors, and that detected ammonium originated from within the tumor

  9. Visible-light-mediated selective arylation of cysteine in batch and flow

    NARCIS (Netherlands)

    Bottecchia, C.; Rubens, M.; Gunnoo, S.B.; Hessel, V.; Madder, A.

    2017-01-01

    A mild visible-light-mediated strategy for cysteine arylation is presented. The method relies on the use of eosin Y as a metal-free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation

  10. Development of multiplex loop mediated isothermal amplification (m-LAMP) label-based gold nanoparticles lateral flow dipstick biosensor for detection of pathogenic Leptospira.

    Science.gov (United States)

    Nurul Najian, A B; Engku Nur Syafirah, E A R; Ismail, Nabilah; Mohamed, Maizan; Yean, Chan Yean

    2016-01-15

    In recent years extensive numbers of molecular diagnostic methods have been developed to meet the need of point-of-care devices. Efforts have been made towards producing rapid, simple and inexpensive DNA tests, especially in the diagnostics field. We report on the development of a label-based lateral flow dipstick for the rapid and simple detection of multiplex loop-mediated isothermal amplification (m-LAMP) amplicons. A label-based m-LAMP lateral flow dipstick assay was developed for the simultaneous detection of target DNA template and a LAMP internal control. This biosensor operates through a label based system, in which probe-hybridization and the additional incubation step are eliminated. We demonstrated this m-LAMP assay by detecting pathogenic Leptospira, which causes the re-emerging disease Leptospirosis. The lateral flow dipstick was developed to detect of three targets, the LAMP target amplicon, the LAMP internal control amplicon and a chromatography control. Three lines appeared on the dipstick, indicating positive results for all representative pathogenic Leptospira species, whereas two lines appeared, indicating negative results, for other bacterial species. The specificity of this biosensor assay was 100% when it was tested with 13 representative pathogenic Leptospira species, 2 intermediate Leptospira species, 1 non-pathogenic Leptospira species and 28 other bacteria species. This study found that this DNA biosensor was able to detect DNA at concentrations as low as 3.95 × 10(-1) genomic equivalent ml(-1). An integrated m-LAMP and label-based lateral flow dipstick was successfully developed, promising simple and rapid visual detection in clinical diagnostics and serving as a point-of-care device. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Flexible Mediation Analysis With Multiple Mediators.

    Science.gov (United States)

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. EEG Correlates of the Flow State: A Combination of Increased Frontal Theta and Moderate Frontocentral Alpha Rhythm in the Mental Arithmetic Task

    Directory of Open Access Journals (Sweden)

    Kenji Katahira

    2018-03-01

    Full Text Available Flow experience is a subjective state experienced during holistic involvement in a certain activity, which has been reported to function as a factor promoting motivation, skill development, and better performance in the activity. To verify the positive effects of flow and develop a method to utilize it, the establishment of a reliable measurement of the flow state is essential. The present study utilized an electroencephalogram (EEG during an experimentally evoked flow state and examined the possibility of objective measurement of immediate flow. A total of 16 participants (10 males, 6 females participated in the experiment that employed a mental arithmetic task developed in a previous study. Post-trial self-report of the flow state and EEG during task execution were measured and compared among three conditions (Boredom, Flow, and Overload that had different levels of task difficulty. Furthermore, the correlations between subjective flow items and EEG activity were examined. As expected, the ratings on the subjective evaluation items representing the flow state were the highest in the Flow condition. Regarding the EEG data, theta activities in the frontal areas were higher in the Flow and the Overload conditions than in the Boredom condition, and alpha activity in the frontal areas and the right central area gradually increased depending on the task difficulty. These EEG activities correlated with self-reported flow experience, especially items related to the concentration on the task and task difficulty. From the results, the flow state was characterized by increased theta activities in the frontal areas and moderate alpha activities in the frontal and central areas. The former may be related to a high level of cognitive control and immersion in task, and the latter suggests that the load on the working memory was not excessive. The findings of this study suggest the possibility of distinguishing the flow state from other states using multiple

  13. EEG Correlates of the Flow State: A Combination of Increased Frontal Theta and Moderate Frontocentral Alpha Rhythm in the Mental Arithmetic Task.

    Science.gov (United States)

    Katahira, Kenji; Yamazaki, Yoichi; Yamaoka, Chiaki; Ozaki, Hiroaki; Nakagawa, Sayaka; Nagata, Noriko

    2018-01-01

    Flow experience is a subjective state experienced during holistic involvement in a certain activity, which has been reported to function as a factor promoting motivation, skill development, and better performance in the activity. To verify the positive effects of flow and develop a method to utilize it, the establishment of a reliable measurement of the flow state is essential. The present study utilized an electroencephalogram (EEG) during an experimentally evoked flow state and examined the possibility of objective measurement of immediate flow. A total of 16 participants (10 males, 6 females) participated in the experiment that employed a mental arithmetic task developed in a previous study. Post-trial self-report of the flow state and EEG during task execution were measured and compared among three conditions (Boredom, Flow, and Overload) that had different levels of task difficulty. Furthermore, the correlations between subjective flow items and EEG activity were examined. As expected, the ratings on the subjective evaluation items representing the flow state were the highest in the Flow condition. Regarding the EEG data, theta activities in the frontal areas were higher in the Flow and the Overload conditions than in the Boredom condition, and alpha activity in the frontal areas and the right central area gradually increased depending on the task difficulty. These EEG activities correlated with self-reported flow experience, especially items related to the concentration on the task and task difficulty. From the results, the flow state was characterized by increased theta activities in the frontal areas and moderate alpha activities in the frontal and central areas. The former may be related to a high level of cognitive control and immersion in task, and the latter suggests that the load on the working memory was not excessive. The findings of this study suggest the possibility of distinguishing the flow state from other states using multiple EEG activities

  14. Influence of immune-mediated hemolytic anemia on flow velocities in the portal vein and caudal vena cava measured by use of pulsed-wave Doppler ultrasonography in dogs.

    Science.gov (United States)

    Smith, Rachel Policelli; Koenigshof, Amy M; Smith, Daniel J; Strom, Phillip R; Nelson, Nathan C

    2018-05-01

    OBJECTIVE To compare blood flow velocities of the portal vein (PV) and caudal vena cava (CVC) measured by use of pulsed-wave Doppler ultrasonography in clinically normal dogs and dogs with primary immune-mediated hemolytic anemia (IMHA). ANIMALS 11 client-owned dogs admitted to a veterinary teaching hospital for management of primary IMHA and 21 staff- or student-owned clinically normal dogs. PROCEDURES Flow velocities in the PV and CVC at the porta hepatis were evaluated in conscious unsedated dogs with concurrent ECG monitoring; evaluations were performed before dogs with IMHA received heparin or blood transfusions. Three measurements of peak velocity at end expiration were obtained for each vessel, and the mean was calculated. Results were compared between IMHA and control groups. RESULTS Mean ± SD blood flow velocity in the CVC differed between control (63.0 ± 18.6 cm/s) and IMHA (104 ± 36.9 cm/s) groups. Variance in dogs with IMHA was significantly greater than that for the clinically normal dogs. No significant difference in blood flow velocity in the PV was detected between IMHA and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Higher blood flow velocities were detected by use of pulsed-wave Doppler ultrasonography in the CVC of dogs with naturally occurring IMHA and may be used to predict anemia in patients suspected of having IMHA.

  15. Behaviourally mediated indirect effects : interference competition increases predation mortality in foraging redshanks

    NARCIS (Netherlands)

    Minderman, J; Lind, J; Cresswell, W

    The effect of competition for a limiting resource on the population dynamics of competitors is usually assumed to operate directly through starvation, yet may also affect survival indirectly through behaviourally mediated effects that affect risk of predation. Thus, competition can affect more than

  16. Intracellular Kinases Mediate Increased Translation and Secretion of Netrin-1 from Renal Tubular Epithelial Cells

    Science.gov (United States)

    Jayakumar, Calpurnia; Mohamed, Riyaz; Ranganathan, Punithavathi Vilapakkam; Ramesh, Ganesan

    2011-01-01

    Background Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury. Methods and Principal Findings Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. Conclusion Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells. PMID:22046354

  17. Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells.

    Directory of Open Access Journals (Sweden)

    Calpurnia Jayakumar

    Full Text Available BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS to determine the signaling pathways that regulate netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS: Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.

  18. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  19. Increased resiliency and activity of microbial mediated carbon cycling enzymes in diversified bioenergy cropping systems

    Science.gov (United States)

    Upton, R.; Bach, E.; Hofmockel, K. S.

    2017-12-01

    Microbes are mediators of soil carbon (C) and are influenced in membership and activity by nitrogen (N) fertilization and inter-annual abiotic factors. Microbial communities and their extracellular enzyme activities (EEA) are important parameters that influence ecosystem C cycling properties and are often included in microbial explicit C cycling models. In an effort to generate model relevant, empirical findings, we investigated how both microbial community structure and C degrading enzyme activity are influenced by inter-annual variability and N inputs in bioenergy crops. Our study was performed at the Comparison of Biofuel Systems field-site from 2011 to 2014, in three bioenergy cropping systems, continuous corn (CC) and two restored prairies, both fertilized (FP) and unfertilized (P). We hypothesized microbial community structure would diverge during the prairie restoration, leading to changes in C cycling enzymes over time. Using a sequencing approach (16S and ITS) we determined the bacterial and fungal community structure response to the cropping system, fertilization, and inter-annual variability. Additionally, we used EEA of β-glucosidase, cellobiohydrolase, and β-xylosidase to determine inter-annual and ecosystem impacts on microbial activity. Our results show cropping system was a main effect for microbial community structure, with corn diverging from both prairies to be less diverse. Inter-annual changes showed that a drought occurring in 2012 significantly impacted microbial community structure in both the P and CC, decreasing microbial richness. However, FP increased in microbial richness, suggesting the application of N increased resiliency to drought. Similarly, the only year in which C cycling enzymes were impacted by ecosystem was 2012, with FP supporting higher potential enzymatic activity then CC and P. The highest EEA across all ecosystems occurred in 2014, suggesting the continued root biomass and litter build-up in this no till system

  20. Study of gene flow from GM cotton (Gossypium hirsutum) varieties in El Espinal (Tolima, Colombia)

    International Nuclear Information System (INIS)

    Rache Cardenal, Leidy Yanira; Mora Oberlaender, Julian; Chaparro Giraldo, Alejandro

    2013-01-01

    In 2009, 4088 hectares of genetically modified (GM) cotton were planted in Tolima (Colombia), however there is some uncertainty about containment measures needed to prevent the flow of pollen and seed from regulated GM fields into adjacent fields. In this study, the gene flow from GM cotton varieties to conventional or feral cotton plants via seed and pollen was evaluated. ImmunostripTM, PCR and ELISA assays were used to detect gene flow. Fifty six refuges, 27 fields with conventional cotton and four feral individuals of the enterprise Remolinos Inc. located in El Espinal (Tolima) were analyzed in the first half of 2010. The results indicated seed mediated gene flow in 45 refuges (80.4 %) and 26 fields with conventional cotton (96 %), besides pollen mediated gene flow in one field with conventional cotton and nine refuges. All fields cultivated with conventional cotton showed gene flow from GM cotton. Two refuges and two feral individuals did not reveal gene flow from GM cotton.

  1. Superoxide dismutase levels and peak expiratory flow in asthmatic children

    Directory of Open Access Journals (Sweden)

    Arie Kurniasih

    2016-11-01

    Full Text Available Background Asthma is a chronic inflammatory process which involve variety of cells such as inflammatory mediators, reactive oxygen species (ROS, and cytokines. The inflammatory process would be exacerbated in the presence of oxidative stress. Superoxide dismutase (SOD is the first important enzyme to protect the respiratory tract against oxidative stress. The decreased of SOD has a correlation with increased of airway obstruction and bronchospasm. Objective To assess for a correlation between superoxide dismutase (SOD levels and peak expiratory flow, as well as to determine the impact of SOD levels for predicting asthma attacks. Methods We conducted a prospective cohort study at Dr. Sardjito Hospital, Yogyakarta, between February and April 2011 involving asthmatic children aged 5-18 years. Subjects’ serum SOD levels and peak expiratory flow were measured at the same time point. We then performed a prospective study following up on the same subjects to find out if they had a recurrent asthma attack within one month of the tests. We also reassessed their peak expiratory flow one month after blood specimens were obtained. Results Thirty-nine patients were enrolled in this study. There was no significant correlation between SOD level and peak expiratory flow [r=0.289; 95%CI -0.025 to 0.47; P=0.074]. However, older age was significantly associated with higher peak expiratory flow (=0.5; 95%CI 3.10 to 11.57; P=0.01. Lower levels of SOD increased the risk of asthma attacks in a month following the initial measurements (RR=5.5; 95%CI 1.6 to 18.9; P=0.009. Conclusion Superoxide dismutase (SOD level is not significantly associated with peak expiratory flow. However, we find a relationship between older age and higher peak expiratory flow and a relationship between lower SOD levels and risk of asthma attacks within one month following the tests.

  2. Chitosan inhibits platelet-mediated clot retraction, increases platelet-derived growth factor release, and increases residence time and bioactivity of platelet-rich plasma in vivo.

    Science.gov (United States)

    Deprés-Tremblay, Gabrielle; Chevrier, Anik; Tran-Khanh, Nicolas; Nelea, Monica; Buschmann, Michael D

    2017-11-10

    Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.

  3. GPR68 Senses Flow and Is Essential for Vascular Physiology.

    Science.gov (United States)

    Xu, Jie; Mathur, Jayanti; Vessières, Emilie; Hammack, Scott; Nonomura, Keiko; Favre, Julie; Grimaud, Linda; Petrus, Matt; Francisco, Allain; Li, Jingyuan; Lee, Van; Xiang, Fu-Li; Mainquist, James K; Cahalan, Stuart M; Orth, Anthony P; Walker, John R; Ma, Shang; Lukacs, Viktor; Bordone, Laura; Bandell, Michael; Laffitte, Bryan; Xu, Yan; Chien, Shu; Henrion, Daniel; Patapoutian, Ardem

    2018-04-19

    Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Local arginase inhibition during early reperfusion mediates cardioprotection via increased nitric oxide production.

    Directory of Open Access Journals (Sweden)

    Adrian T Gonon

    Full Text Available Consumption of L-arginine contributes to reduced bioavailability of nitric oxide (NO that is critical for the development of ischemia-reperfusion injury. The aim of the study was to determine myocardial arginase expression and activity in ischemic-reperfusion myocardium and whether local inhibition of arginase within the ischemic myocardium results in increased NO production and protection against myocardial ischemia-reperfusion. Anesthetized pigs were subjected to coronary artery occlusion for 40 min followed by 4 h reperfusion. The pigs were randomized to intracoronary infusion of vehicle (n = 7, the arginase inhibitor N-hydroxy-nor-L-arginine (nor-NOHA, 2 mg/min, n = 7, the combination of nor-NOHA and the NO synthase inhibitor N(G-monomethyl-L-arginine (L-NMMA, 0.35 mg/min, n = 6 into the jeopardized myocardial area or systemic intravenous infusion of nor-NOHA (2 mg/min, n = 5 at the end of ischemia and start of reperfusion. The infarct size of the vehicle group was 80 ± 4% of the area at risk. Intracoronary nor-NOHA reduced infarct size to 46 ± 5% (P<0.01. Co-administration of L-NMMA abrogated the cardioprotective effect mediated by nor-NOHA (infarct size 72 ± 6%. Intravenous nor-NOHA did not reduce infarct size. Arginase I and II were expressed in cardiomyocytes, endothelial, smooth muscle and poylmorphonuclear cells. There was no difference in cytosolic arginase I or mitochondrial arginase II expression between ischemic-reperfused and non-ischemic myocardium. Arginase activity increased 2-fold in the ischemic-reperfused myocardium in comparison with non-ischemic myocardium. In conclusion, ischemia-reperfusion increases arginase activity without affecting cytosolic arginase I or mitochondrial arginase II expression. Local arginase inhibition during early reperfusion reduces infarct size via a mechanism that is dependent on increased bioavailability of NO.

  5. Mediation and Counseling Services: A Viable Partnership

    Science.gov (United States)

    Hodges, Shannon

    2009-01-01

    Mediation has become common in many areas of society, including marital dissolution, community disputes, governmental agencies, and business and industry. Though higher education has been slower than society to adopt mediation services, campus mediation is becoming increasingly more common. This article explains why mediation is a viable…

  6. Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dong Hou

    2018-07-01

    Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer

  7. Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

    Science.gov (United States)

    Roccatello, D; Mengozzi, G; Ferro, M; Cesano, G; Polloni, R; Mosso, R; Bonetti, G; Inconis, T; Paradisi, L; Sena, L M

    1995-09-01

    An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p effective renal plasma flow (p counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

  8. Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Aβ levels

    Directory of Open Access Journals (Sweden)

    Dicker Bridget L

    2007-06-01

    Full Text Available Abstract Background Alzheimer's disease (AD is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ in extracellular plaques. Mutations in amyloid precursor protein (APP and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD. Results Adeno-associated viral (AAV vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits. Conclusion The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in

  9. Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.

    Science.gov (United States)

    Barker, Catherine R; McNamara, Anne V; Rackstraw, Stephen A; Nelson, David E; White, Mike R; Watson, Alastair J M; Jenkins, John R

    2006-01-01

    Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.

  10. The Effect of a Shear Flow on the Uptake of LDL and Ac-LDL by Cultured Vascular Endothelial Cells

    Science.gov (United States)

    Niwa, Koichi; Karino, Takeshi

    The effects of a shear flow on the uptake of fluorescence-labeled low-density lipoprotein (DiI-LDL), acetylated LDL (DiI-Ac-LDL), and lucifer yellow (LY; a tracer of fluid-phase endocytosis) by cultured bovine aortic ECs were studied using a rotating-disk shearing apparatus. It was found that 2hours’ exposure of ECs to a laminar shear flow that imposed ECs an area-mean shear stress of 10dynes/cm2 caused an increase in the uptake of DiI-LDL and LY. By contrast, the uptake of DiI-Ac-LDL was decreased by exposure of the ECs to a shear flow. Addition of dextran sulfate (DS), a competitive inhibitor of scavenger receptors, reversed the effect of a shear flow on the uptake of DiI-Ac-LDL, resulting in an increase by the imposition of a shear flow, while the uptake of DiI-LDL and LY remained unaffected. It was concluded that a shear flow promotes the endocytosis of DiI-LDL and LY by ECs, but suppresses the uptake of DiI-Ac-LDL by ECs by inhibiting scavenger receptor-mediated endocytosis.

  11. Increasing power generation in horizontal axis wind turbines using optimized flow control

    Science.gov (United States)

    Cooney, John A., Jr.

    In order to effectively realize future goals for wind energy, the efficiency of wind turbines must increase beyond existing technology. One direct method for achieving increased efficiency is by improving the individual power generation characteristics of horizontal axis wind turbines. The potential for additional improvement by traditional approaches is diminishing rapidly however. As a result, a research program was undertaken to assess the potential of using distributed flow control to increase power generation. The overall objective was the development of validated aerodynamic simulations and flow control approaches to improve wind turbine power generation characteristics. BEM analysis was conducted for a general set of wind turbine models encompassing last, current, and next generation designs. This analysis indicated that rotor lift control applied in Region II of the turbine power curve would produce a notable increase in annual power generated. This was achieved by optimizing induction factors along the rotor blade for maximum power generation. In order to demonstrate this approach and other advanced concepts, the University of Notre Dame established the Laboratory for Enhanced Wind Energy Design (eWiND). This initiative includes a fully instrumented meteorological tower and two pitch-controlled wind turbines. The wind turbines are representative in their design and operation to larger multi-megawatt turbines, but of a scale that allows rotors to be easily instrumented and replaced to explore new design concepts. Baseline data detailing typical site conditions and turbine operation is presented. To realize optimized performance, lift control systems were designed and evaluated in CFD simulations coupled with shape optimization tools. These were integrated into a systematic design methodology involving BEM simulations, CFD simulations and shape optimization, and selected experimental validation. To refine and illustrate the proposed design methodology, a

  12. Sufentanil does not increase cerebral blood flow in healthy human volunteers

    International Nuclear Information System (INIS)

    Mayer, N.; Weinstabl, C.; Podreka, I.; Spiss, C.K.

    1990-01-01

    The effect of sufentanil on human cerebral blood flow (CBF) was studied in seven unpremedicated, healthy volunteers 31 +/- 3.5 yr of age (mean +/- SD) and either sex. CBF (ml.100 g-1.min-1) was measured noninvasively with the 133Xe clearance technique and a scintillation camera before and after sufentanil 0.5 micrograms/kg administered intravenously. This technique provides values for global blood flow and for gray and white matter blood flow, and from 13 preselected regions in one hemisphere. After the administration of sufentanil, the volunteers were stimulated verbally in order to prevent their loss of consciousness and hypercarbia. Heart rate (HR), arterial pressure, oxyhemoglobin saturation, and end-tidal CO2 ETCO2 were recorded during the measurements. Neither global CBF (46.1 +/- 1.6 control and 43 +/- 1.9 after sufentanil, mean +/- SEM) nor gray (76.5 +/- 3.2 and 70.9 +/- 6.1) or white (22.7 +/- 1.5 and 24.2 +/- 1.6) matter blood flow changed significantly after sufentanil administration. As well, no significant differences in HR (72 +/- 4 control and 79 +/- 4 beats per min after sufentanil) and ETCO2 (39.8 +/- 1.4 and 41.1 +/- 1.1 mmHg) were observed. It is concluded that sufentanil has no significant effect on CBF in healthy human volunteers

  13. From Mediatized Emotion to Digital Affect Cultures: New Technologies and Global Flows of Emotion

    OpenAIRE

    Katrin Döveling; Anu A. Harju; Denise Sommer

    2018-01-01

    Research on the processes of mediatization aims to explore the mutual shaping of media and social life and how new media technologies influence and infiltrate social practices and cultural life. We extend this discussion of media’s role in transforming the everyday by including in the discussion the mediatization of emotion and discuss what we conceptualize as digital affect culture(s). We understand these as relational, contextual, globally emergent spaces in the digital environment where af...

  14. Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.

    Science.gov (United States)

    Lee, Dooyoung; Kim, Jiyeon; Beste, Michael T; Koretzky, Gary A; Hammer, Daniel A

    2012-06-01

    T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.

  15. Flow enhances photosynthesis in marine benthic autotrophs by increasing the efflux of oxygen from the organism to the water.

    Science.gov (United States)

    Mass, Tali; Genin, Amatzia; Shavit, Uri; Grinstein, Mor; Tchernov, Dan

    2010-02-09

    Worldwide, many marine coastal habitats are facing rapid deterioration due in part to human-driven changes in habitat characteristics, including changes in flow patterns, a factor known to greatly affect primary production in corals, algae, and seagrasses. The effect of flow traditionally is attributed to enhanced influx of nutrients and dissolved inorganic carbon (DIC) across the benthic boundary layer from the water to the organism however, here we report that the organism's photosynthetic response to changes in the flow is nearly instantaneous, and that neither nutrients nor DIC limits this rapid response. Using microelectrodes, dual-pulse amplitude-modulated fluorometry, particle image velocimetry, and real time mass-spectrometry with the common scleractinian coral Favia veroni, the alga Gracilaria cornea, and the seagrass Halophila stipulacea, we show that this augmented photosynthesis is due to flow-driven enhancement of oxygen efflux from the organism to the water, which increases the affinity of the RuBisCO to CO(2). No augmentation of photosynthesis was found in the absence of flow or when flow occurred, but the ambient concentration of oxygen was artificially elevated. We suggest that water motion should be considered a fundamental factor, equivalent to light and nutrients, in determining photosynthesis rates in marine benthic autotrophs.

  16. Augmentation of forced flow boiling heat transfer by introducing air flow into subcooled water flow

    International Nuclear Information System (INIS)

    Koizumi, Y.; Ohtake, H.; Yuasa, T.; Matsushita, N.

    2001-01-01

    The effect of air injection into a subcooled water flow on boiling heat transfer and a critical heat flux (CHF) was examined experimentally. Experiments were conducted in the range of subcooling of 50 K, a superficial velocity of water and air Ul = 0.17 ∼ 3.4 and Ug = 0 ∼ 15 m/s, respectively. A test heat transfer surface was a 5 mm wide, 40 mm long and 0.5 mm thick stainless steel sheet embedded on the bottom wall of a 10 mm high and 20 mm wide rectangular flow channel. Nine times enhancement of the heat transfer coefficient in the non-boiling region was attained at the most by introducing an air flow into a water single-phase flow. The heat transfer improvement was prominent when the water flow rate was low and the air introduction was large. The present results of the non-boiling heat transfer were well correlated with the Lockhart-Martinelli parameter X tt ; h TP /h L0 = 5.0(1/ X tt ) 0.5 . The air introduction has some effect on the augmentation of heat transfer in the boiling region, however, the two-phase flow effect was little and the boiling was dominant in the fully developed boiling region. The CHF was improved a little by the air introduction in the high water flow region. However, that was rather greatly reduced in the low flow region. Even so, the general trend by the air introduction was that qCHF increased as the air introduction was increased. The heat transfer augmentation in the non-boiling region was attained by less power increase than that in the case that only the water flow rate was increased. From the aspect of the power consumption and the heat transfer enhancement, the small air introduction in the low water flow rate region seemed more profitable, although the air introduction in the high water flow rate region and also the large air introduction were still effective in the augmentation of the heat transfer in the non-boiling region. (author)

  17. Role of bronchodilation and pattern of breathing in increasing tidal expiratory flow with progressive induced hypercapnia in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Finucane, Kevin E; Singh, Bhajan

    2018-01-01

    Hypercapnia (HC) in vitro relaxes airway smooth muscle; in vivo, it increases respiratory effort, tidal expiratory flows (V̇ exp ), and, by decreasing inspiratory duration (Ti), increases elastic recoil pressure (Pel) via lung viscoelasticity; however, its effect on airway resistance is uncertain. We examined the contributions of bronchodilation, Ti, and expiratory effort to increasing V̇ exp with progressive HC in 10 subjects with chronic obstructive pulmonary disease (COPD): mean forced expiratory volume in 1 s (FEV 1 ) 53% predicted. Lung volumes (Vl), V̇ exp , esophageal pressure (Pes), Ti, and end-tidal Pco 2 ([Formula: see text]) were measured during six tidal breaths followed by an inspiratory capacity (IC), breathing air, and at three levels of HC. V̇ exp and V̇ with submaximal forced vital capacities breathing air (V̇ sFVC ) were compared. Pulmonary resistance ( Rl) was measured from the Pes-V̇ relationship. V̇ exp and Pes at end-expiratory lung volume (EELV) + 0.3 tidal volume [V̇ (0.3Vt) and Pes (0.3Vt) , respectively], Ti, and Rl correlated with [Formula: see text] ( P pulmonary disease (COPD), progressive HC increases tidal expiratory flows by inducing bronchodilation and via an increased rate of inspiration and lung viscoelasticity, a probable increase in lung elastic recoil pressure, both changes increasing expiratory flows, promoting lung emptying and a stable end-expiratory volume. Bronchodilation with HC occurred despite optimal standard bronchodilator therapy, suggesting that in COPD further bronchodilation is possible.

  18. Understanding Mediation Support

    OpenAIRE

    Lanz, David; Pring, Jamie; von Burg, Corinne; Zeller, Mathias

    2017-01-01

    Recent decades have witnessed increasing institutionalization of mediation support through the establishment of mediation support structures (MSS) within foreign ministries and secretariats of multilateral organizations. This study sheds light on this trend and aims to better understand the emergence, design and development of different MSS. This study analyzes six MSS, namely those established in the United Nations (UN), the Organization for Security and Co-operation in Europe (OSCE), the Eu...

  19. Oxygen and Glucose Deprivation Induces Bergmann Glia Membrane Depolarization and Ca2+ Rises Mainly Mediated by K+ and ATP Increases in the Extracellular Space

    Directory of Open Access Journals (Sweden)

    Romain Helleringer

    2017-11-01

    Full Text Available During brain ischemia, intense energy deficiency induces a complex succession of events including pump failure, acidosis and exacerbated glutamate release. In the cerebellum, glutamate is the principal mediator of Purkinje neuron anoxic depolarization during episodes of oxygen and glucose deprivation (OGD. Here, the impact of OGD is studied in Bergmann glia, specialized astrocytes closely associated to Purkinje neurons. Patch clamp experiments reveal that during OGD Bergmann glial cells develop a large depolarizing current that is not mediated by glutamate and purinergic receptors but is mainly due to the accumulation of K+ in the extracellular space. Furthermore, we also found that increases in the intracellular Ca2+ concentration appear in Bergmann glia processes several minutes following OGD. These elevations require, in an early phase, Ca2+ mobilization from internal stores via P2Y receptor activation, and, over longer periods, Ca2+ entry through store-operated calcium channels. Our results suggest that increases of K+ and ATP concentrations in the extracellular space are primordial mediators of the OGD effects on Bergmann glia. In the cerebellum, glial responses to energy deprivation-triggering events are therefore highly likely to follow largely distinct rules from those of their neuronal counterparts.

  20. Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

    Science.gov (United States)

    Kelly, Meredith A; Pavlicova, Martina; Glass, Andrew; Mariani, John J; Bisaga, Adam; Sullivan, Maria A; Nunes, Edward V; Levin, Frances R

    2014-11-01

    Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. A model of hydraulic interactions in liver parenchyma as forces behind the intrahepatic bile flow.

    Science.gov (United States)

    Kurbel, S; Kurbel, B; Dmitrovic, B; Wagner, J

    2001-05-01

    The small diameters of bile canaliculi and interlobular bile ducts make it hard to attribute the bile flow solely to the process of secretion. In the model liver within its capsule is considered a limited space in which volume expansions of one part are possible only through the shrinking of other parts. The liver capsule allows only very slow volume changes. The rate of blood flow through the sinusoides is governed by the Poisseuill-Hagen law. The model is based on a concept of circulatory liver units. A unit would contain a group of acini sharing the same conditions of arterial flow. We can imagine them as an acinar group behind the last pressure reducer on one arterial branch. Acini from neighboring units compose liver lobules and drain through the same central venule. One lobule can contain acini from several neighboring circulatory units. The perfusion cycle in one unit begins with a transient tide in the arterial flow, governed by local mediators. Corresponding acini expand, grabbing the space by compressing their neighbors in the same lobules. Vascular resistance is reduced in dilated and increased in compressed acini. Portal blood flows through the dilated acini, bypassing the compressed neighbors. The cycle ends when the portal tide slowly diminishes and acinar volume is back on the interphase value until the new perfusion cycle is started in another circulatory unit. Each cycle probably takes minutes to complete. Increased pressures both in dilated and in compressed acini force the bile to move from acinar canalicules. Both up and down changes in acinar volume might force the acinar biliary flow. In cases of arterial vasoconstriction, increased activity of vasoactive substances would keep most of the circulatory units in the interphase and increased liver resistance can be expected. Liver fibrosis makes all acini to be of fixed volume and result in increased resistance. Because of that, low pressure portal flow would be more compromised, as reported. In

  2. Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway

    OpenAIRE

    Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M.; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

    2016-01-01

    Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transiti...

  3. Cyclic electron flow provides acclimatory plasticity for the photosynthetic machinery under various environmental conditions and developmental stages

    Directory of Open Access Journals (Sweden)

    Marjaana eSuorsa

    2015-09-01

    Full Text Available Photosynthetic electron flow operates in two modes, linear and cyclic. In cyclic electron flow (CEF, electrons are recycled around photosystem I. As a result, a transthylakoid proton gradient (ΔpH is generated, leading to the production of ATP without concomitant production of NADPH, thus increasing the ATP/NADPH ratio within the chloroplast. At least two routes for CEF exist: a PGR5-PGRL1–and a chloroplast NDH-like complex mediated pathway. This review focuses on recent findings concerning the characteristics of both CEF routes in higher plants, with special emphasis paid on the crucial role of CEF in under challenging environmental conditions and developmental stages.

  4. Hydrodynamic property of the cytoplasm is sufficient to mediate cytoplasmic streaming in the Caenorhabiditis elegans embryo

    Science.gov (United States)

    Niwayama, Ritsuya; Shinohara, Kyosuke; Kimura, Akatsuki

    2011-01-01

    Cytoplasmic streaming is a type of intracellular transport widely seen in nature. Cytoplasmic streaming in Caenorhabditis elegans at the one-cell stage is bidirectional; the flow near the cortex (“cortical flow”) is oriented toward the anterior, whereas the flow in the central region (“cytoplasmic flow”) is oriented toward the posterior. Both cortical flow and cytoplasmic flow depend on non-muscle-myosin II (NMY-2), which primarily localizes in the cortex. The manner in which NMY-2 proteins drive cytoplasmic flow in the opposite direction from remote locations has not been fully understood. In this study, we demonstrated that the hydrodynamic properties of the cytoplasm are sufficient to mediate the forces generated by the cortical myosin to drive bidirectional streaming throughout the cytoplasm. We quantified the flow velocities of cytoplasmic streaming using particle image velocimetry (PIV) and conducted a three-dimensional hydrodynamic simulation using the moving particle semiimplicit method. Our simulation quantitatively reconstructed the quantified flow velocity distribution resolved through PIV analysis. Furthermore, our PIV analyses detected microtubule-dependent flows during the pronuclear migration stage. These flows were reproduced via hydrodynamic interactions between moving pronuclei and the cytoplasm. The agreement of flow dynamics in vivo and in simulation indicates that the hydrodynamic properties of the cytoplasm are sufficient to mediate cytoplasmic streaming in C. elegans embryos. PMID:21730185

  5. Decreased muscle oxygenation and increased arterial blood flow in the non-exercising limb during leg exercise.

    Science.gov (United States)

    Shiroishi, Kiyoshi; Kime, Ryotaro; Osada, Takuya; Murase, Norio; Shimomura, Kousuke; Katsumura, Toshihito

    2010-01-01

    We evaluated arterial blood flow, muscle tissue oxygenation and muscle metabolism in the non-exercising limb during leg cycling exercise. Ten healthy male volunteers performed a graded leg cycling exercise at 0, 40, 80, 120 and 160 watts (W) for 5 min each. Tissue oxygenation index (TOI) of the non-exercising left forearm muscle was measured using a near-infrared spatially resolved spectroscopy (NIR(SRS)), and non-exercising forearm blood flow ((NONEX)FBF) in the brachial artery was also evaluated by a Doppler ultrasound system. We also determined O(2) consumption of the non-exercising forearm muscle (NONEXV(O)(2mus)) by the rate of decrease in O(2)Hb during arterial occlusion at each work rate. TOI was significantly decreased at 160 W (p exercising muscle may be reduced, even though (NONEX)FBF increases at high work rates during leg cycling exercise.

  6. Far-infrared radiation acutely increases nitric oxide production by increasing Ca(2+) mobilization and Ca(2+)/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179.

    Science.gov (United States)

    Park, Jung-Hyun; Lee, Sangmi; Cho, Du-Hyong; Park, Young Mi; Kang, Duk-Hee; Jo, Inho

    2013-07-12

    Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser(1179)) in a time-dependent manner (up to 40min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca(2+) levels. Treatment with KN-93, a selective inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser(1179) phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser(1179) phosphorylation. This study suggests that FIR radiation increases NO production via increasing CaMKII-mediated eNOS-Ser(1179) phosphorylation but TRPV channels may not be involved in this pathway. Our results may provide the molecular mechanism by which FIR radiation improves endothelial function. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. The effects of gender, flow and video game experience on combat identification training.

    Science.gov (United States)

    Plummer, John Paul; Schuster, David; Keebler, Joseph R

    2017-08-01

    The present study examined the effects of gender, video game experience (VGE), and flow state on multiple indices of combat identification (CID) performance. Individuals were trained on six combat vehicles in a simulation, presented through either a stereoscopic or non-stereoscopic display. Participants then reported flow state, VGE and were tested on their ability to discriminate friend vs. foe and identify both pictures and videos of the trained vehicles. The effect of stereoscopy was not significant. There was an effect of gender across three dependent measures. For the two picture-based measures, the effect of gender was mediated by VGE. Additionally, the effect of gender was moderated by flow state on the identification measures. Overall, the study suggests that gender differences may be overcome by VGE and by achieving flow state. Selection based on these individual differences may be useful for future military simulation. Practitioner Summary: This work investigates the effect of gender, VGE and flow state on CID performance. For three measures of performance, there was a main effect of gender. Gender was mediated by previous VGE on two measures, and gender was moderated by flow state on two measures.

  8. Strain and Ferroelectric-Field Effects Co-mediated Magnetism in (011)-CoFe2O4/Pb(Mg1/3Nb2/3)0.7Ti0.3O3Multiferroic Heterostructures

    KAUST Repository

    Wang, Ping

    2016-08-19

    Electric-field mediated magnetism was investigated in CoFe2O4 (CFO, deposited by reactive cosputtering under different Oxygen flow rates) films fabricated on (011)-Pb(Mg1/3Nb2/3)(0.7)Ti0.3O3 (PMN-PT) substrates. Ascribed to the volatile strain effect of PMN-PT, the magnetization of the CFO films decreases along the [01-1] direction whereas it increases along the [100] direction under the electric field, which is attributed to the octahedron distortion in the spinel ferrite. Moreover, a nonvolatile mediation was obtained in the CFO film with low oxygen flow rate (4 sccm), deriving from the ferroelectric-field effect, in which the magnetization is different after removing the positive and negative fields. The cooperation of the two effects produces four different magnetization states in the CFO film with low oxygen flow rate (4 sccm), compared to the only two different states in the CFO film with high oxygen flow rate (10 sccm). It is suggested that the ferroelectric-field effect is related to the oxygen vacancies in CFO films.

  9. TradeWind Deliverable 5.1: Effects of increasing wind power penetration on the power flows in European grids

    DEFF Research Database (Denmark)

    Lemström, Bettina; Uski-Joutsenvuo, Sanna; Holttinen, Hannele

    2008-01-01

    This report presents the main activities and results of Work Package 5 – Effects of increasing wind power penetration on the power flows in European grids in the TradeWind project. VTT is the leader of Work Package 5 and carries the overall responsibility of this report. The work is based on power...... flow simulations with a grid and market model developed in TradeWind Work Package 3, led by Sintef Energy Research. VTT, Sintef Energy Research and Risø have carried out the simulations of the different scenarios, analysed the results and written Chapter 4 about the impact of wind power on cross...

  10. Leptospira santorosai Serovar Shermani detergent extract induces an increase in fibronectin production through a Toll-like receptor 2-mediated pathway.

    Science.gov (United States)

    Tian, Ya-Chung; Hung, Cheng-Chieh; Li, Yi-Jung; Chen, Yung-Chang; Chang, Ming-Yang; Yen, Tzung-Hai; Hsu, Hsiang-Hao; Wu, Mai-Szu; Phillips, Aled; Yang, Chih-Wei

    2011-03-01

    Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.

  11. Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

    Directory of Open Access Journals (Sweden)

    Elisa Ramos-Sevillano

    Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

  12. Saturated Fats from Butter but Not from Cheese Increase HDL-Mediated Cholesterol Efflux Capacity from J774 Macrophages in Men and Women with Abdominal Obesity.

    Science.gov (United States)

    Brassard, Didier; Arsenault, Benoît J; Boyer, Marjorie; Bernic, Daniela; Tessier-Grenier, Maude; Talbot, Denis; Tremblay, Angelo; Levy, Emile; Asztalos, Bela; Jones, Peter J H; Couture, Patrick; Lamarche, Benoît

    2018-04-01

    Recent evidence suggests that the association between dietary saturated fatty acids (SFAs) and coronary artery disease risk varies according to food sources. How SFAs from butter and cheese influence HDL-mediated cholesterol efflux capacity (CEC), a key process in reverse cholesterol transport, is currently unknown. In a predefined secondary analysis of a previously published trial, we have examined how diets rich in SFAs from either cheese or butter influence HDL-mediated CEC, compared with diets rich in either monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs). In a randomized crossover controlled consumption trial, 46 men and women with abdominal obesity consumed 5 isocaloric diets, each for 4 wk. Two diets were rich in SFAs either from cheese (CHEESE) or butter (BUTTER) [12.4-12.6% of energy (%E) as SFAs, 32%E as fat, 52%E as carbohydrates]. In 2 other diets, SFAs (5.8%E) were replaced with either MUFAs from refined olive oil (MUFA) or PUFAs from corn oil (PUFA). Finally, a lower fat and carbohydrate diet was used as a control (5.8%E as SFAs, 25.0%E as fat, 59%E as carbohydrates; CHO). Post-diet HDL-mediated CEC was determined ex vivo using radiolabelled J774 macrophages incubated with apolipoprotein B-depleted serum from the participants. Mean (±SD) age was 41.4 ± 14.2 y, and waist circumference was 107.6 ± 11.5 cm in men and 94.3 ± 12.4 cm in women. BUTTER and MUFA increased HDL-mediated CEC compared with CHEESE (+4.3%, P = 0.026 and +4.7%, P = 0.031, respectively). Exploring the significant diet × sex interaction (P = 0.044) revealed that the increase in HDL-mediated CEC after BUTTER compared with CHEESE was significant among men (+6.0%, P = 0.047) but not women (+2.9%, P = 0.19), whereas the increase after MUFA compared with CHEESE was significant among women (+9.1%, P = 0.008) but not men (-0.6%, P = 0.99). These results provide evidence of a food matrix effect modulating the impact of dairy SFAs on HDL-mediated

  13. Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

    Science.gov (United States)

    Fernandes, Elizabeth S; Russell, Fiona A; Alawi, Khadija M; Sand, Claire; Liang, Lihuan; Salamon, Robin; Bodkin, Jennifer V; Aubdool, Aisah A; Arno, Matthew; Gentry, Clive; Smillie, Sarah-Jane; Bevan, Stuart; Keeble, Julie E; Malcangio, Marzia; Brain, Susan D

    2016-01-11

    The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. We provide evidence that environmental

  14. STUDY OF GENE FLOW FROM GM COTTON (Gossypium hirsutum VARIETIES IN “EL ESPINAL” (TOLIMA, COLOMBIA.

    Directory of Open Access Journals (Sweden)

    Alejandro Chaparro Giraldo

    2013-09-01

    Full Text Available In 2009, 4088 hectares of genetically modified (GM cotton were planted in Tolima (Colombia, however there is some uncertainty about containment measures needed to prevent the flow of pollen and seed from regulated GM fields into adjacent fields. In this study, the gene flow from GM cotton varieties to conventional or feral cotton plants via seed and pollen was evaluated. ImmunostripTM, PCR and ELISA assays were used to detect gene flow. Fifty six refuges, 27 fields with conventional cotton and four feral individuals of the enterprise “Remolinos Inc.” located in El Espinal (Tolima were analyzed in the first half of 2010. The results indicated seeds mediated gene flow in 45 refuges (80,4 % and 26 fields with conventional cotton (96 %, besides a pollen mediated gene flow in one field with conventional cotton and nine refuges. All fields cultivated with conventional cotton showed gene flow from GM cotton. Two refuges and two feral individuals did not reveal gene flow from GM cotton.

  15. Elimination of oral candidiasis may increase stimulated whole salivary flow rate.

    Science.gov (United States)

    Ohga, Noritaka; Yamazaki, Yutaka; Sato, Jun; Asaka, Takuya; Morimoto, Masahiro; Hata, Hironobu; Satoh, Chiharu; Kitagawa, Yoshimasa

    2016-11-01

    Candida infections are frequently encountered fungal infections in the oral mucosa. This study aimed to evaluate the effect of eliminating Candida spp. on stimulated whole salivary flow rate (SWS) in patients with oral candidiasis. This study involved 66 patients with oral candidiasis. Fifty-two consecutive patients, successfully treated by antifungal therapy, were available to examine the effect of elimination of oral Candida spp. on SWS (success group); the 14 patients who tested positive for Candida after therapy were retrospectively included (control group). SWS were used to measure saliva production. Moreover, tongue pain and xerostomia were evaluated using visual analog score (VAS). By eliminating oral Candida spp., SWS significantly increased in the success group after antifungal therapy [SWS: mean value 0.89±0.51ml/min (median 0.82ml/min: 0.15-2.14) to mean value 1.16±0.58ml/min (median 1.05ml/min: 0.2-2.93), Poral Candida spp. in patients with oral candidiasis. Copyright © 2016. Published by Elsevier Ltd.

  16. Interplay between cytoskeletal stresses and cell adaptation under chronic flow.

    Directory of Open Access Journals (Sweden)

    Deepika Verma

    Full Text Available Using stress sensitive FRET sensors we have measured cytoskeletal stresses in α-actinin and the associated reorganization of the actin cytoskeleton in cells subjected to chronic shear stress. We show that long-term shear stress reduces the average actinin stress and this effect is reversible with removal of flow. The flow-induced changes in cytoskeletal stresses are found to be dynamic, involving a transient decrease in stress (phase-I, a short-term increase (3-6 min (Phase-II, followed by a longer-term decrease that reaches a minimum in ~20 min (Phase-III, before saturating. These changes are accompanied by reorganization of the actin cytoskeleton from parallel F-actin bundles to peripheral bundles. Blocking mechanosensitive ion channels (MSCs with Gd(3+ and GsMTx4 (a specific inhibitor eliminated the changes in cytoskeletal stress and the corresponding actin reorganization, indicating that Ca(2+ permeable MSCs participate in the signaling cascades. This study shows that shear stress induced cell adaptation is mediated via MSCs.

  17. HMGB1-mediated DNA bending: Distinct roles in increasing p53 binding to DNA and the transactivation of p53-responsive gene promoters.

    Science.gov (United States)

    Štros, Michal; Kučírek, Martin; Sani, Soodabeh Abbasi; Polanská, Eva

    2018-03-01

    HMGB1 is a chromatin-associated protein that has been implicated in many important biological processes such as transcription, recombination, DNA repair, and genome stability. These functions include the enhancement of binding of a number of transcription factors, including the tumor suppressor protein p53, to their specific DNA-binding sites. HMGB1 is composed of two highly conserved HMG boxes, linked to an intrinsically disordered acidic C-terminal tail. Previous reports have suggested that the ability of HMGB1 to bend DNA may explain the in vitro HMGB1-mediated increase in sequence-specific DNA binding by p53. The aim of this study was to reinvestigate the importance of HMGB1-induced DNA bending in relationship to the ability of the protein to promote the specific binding of p53 to short DNA duplexes in vitro, and to transactivate two major p53-regulated human genes: Mdm2 and p21/WAF1. Using a number of HMGB1 mutants, we report that the HMGB1-mediated increase in sequence-specific p53 binding to DNA duplexes in vitro depends very little on HMGB1-mediated DNA bending. The presence of the acidic C-terminal tail of HMGB1 and/or the oxidation of the protein can reduce the HMGB1-mediated p53 binding. Interestingly, the induction of transactivation of p53-responsive gene promoters by HMGB1 requires both the ability of the protein to bend DNA and the acidic C-terminal tail, and is promoter-specific. We propose that the efficient transactivation of p53-responsive gene promoters by HMGB1 depends on complex events, rather than solely on the promotion of p53 binding to its DNA cognate sites. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Ontogeny of flow-stimulated potassium secretion in rabbit cortical collecting duct: functional and molecular aspects.

    Science.gov (United States)

    Woda, Craig B; Miyawaki, Nobuyuki; Ramalakshmi, Santhanam; Ramkumar, Mohan; Rojas, Raul; Zavilowitz, Beth; Kleyman, Thomas R; Satlin, Lisa M

    2003-10-01

    High urinary flow rates stimulate K secretion in the fully differentiated but not neonatal or weanling rabbit cortical collecting duct (CCD). Both small-conductance secretory K and high-conductance Ca2+/stretch-activated maxi-K channels have been identified in the apical membrane of the mature CCD by patch-clamp analysis. We reported that flow-stimulated net K secretion in the adult rabbit CCD is 1) blocked by TEA and charybdotoxin, inhibitors of intermediate- and high-conductance (maxi-K) Ca2+-activated K channels, and 2) associated with increases in net Na absorption and intracellular Ca2+ concentration ([Ca2+]i). The present study examined whether the absence of flow-stimulated K secretion early in life is due to a 1) limited flow-induced rise in net Na absorption and/or [Ca2+]i and/or 2) paucity of apical maxi-K channels. An approximately sixfold increase in tubular fluid flow rate in CCDs isolated from 4-wk-old rabbits and microperfused in vitro led to an increase in net Na absorption and [Ca2+]i, similar in magnitude to the response observed in 6-wk-old tubules, but it failed to generate an increase in net K secretion. By 5 wk of age, there was a small, but significant, flow-stimulated rise in net K secretion that increased further by 6 wk of life. Luminal perfusion with iberiotoxin blocked the flow stimulation of net K secretion in the adult CCD, confirming the identity of the maxi-K channel in this response. Maxi-K channel alpha-subunit message was consistently detected in single CCDs from animals >/=4 wk of age by RT-PCR. Indirect immunofluorescence microscopy using antibodies directed against the alpha-subunit revealed apical labeling of intercalated cells in cryosections from animals >/=5 wk of age; principal cell labeling was generally intracellular and punctate. We speculate that the postnatal appearance of flow-dependent K secretion is determined by the transcriptional/translational regulation of expression of maxi-K channels. Furthermore, our studies

  19. Effects of supplementation with the fat-soluble vitamins E and D on fasting flow-mediated vasodilation in adults: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Joris, Peter J; Mensink, Ronald P

    2015-03-10

    The effects of fat-soluble vitamin supplementation on cardiovascular disease (CVD) risk are not clear. Therefore, we performed a meta-analysis to quantify effects of fat-soluble vitamin supplements on fasting flow-mediated vasodilation (FMD) of the brachial artery, a validated marker to assess CVD risk. Randomized placebo-controlled trials (RCTs) were identified by a systematic search till July 2014. Seven RCTs studying the effects of vitamin E supplements (range: 300 to 1800 IU per day) and nine RCTs examining the effects of vitamin D supplements, that involved, respectively, 303 and 658 adults, were included. No studies with carotenoid or vitamin K supplements were found. Vitamin E supplementation increased FMD vs. control by 2.42% (95% CI: 0.46% to 4.37%; p = 0.015). No effects of vitamin D supplementation were found (0.15%; 95% CI: -0.21% to 0.51%; p = 0.41). These effects did not depend on subject characteristics, treatment characteristics or technical aspects of the FMD measurement. However, no dose-response relationship was evident for vitamin E, statistical significance depended on one study, while the levels of supplement were far above recommended intakes. The current meta-analysis, therefore, does not provide unambiguous evidence to support the use of fat-soluble vitamin supplements to improve fasting FMD in adults.

  20. The mediatization of ethical consumption

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    Over the years, mediatization studies have investigated the influence of media in numerous sections of contemporary society. One area that has received limited attention is the mediatization of consumption, particularly issues concerning ethical consumption. This article presents a study of how...... mediatization is transforming modern consumption and contributing to the mainstreaming of ethical consumption. Based on a study of a Danish online eco-store, the article argues that modern ethical consumption increasingly depends on new media practices to present sustainable consumption as practical...

  1. Free androgen index as a determinant of arterial stiffness in menopause: a mediation analysis.

    Science.gov (United States)

    Lambrinoudaki, Irene; Georgiopoulos, Georgios A; Athanasouli, Fani; Armeni, Elena; Rizos, Demetrios; Augoulea, Areti; Chatzidou, Sofia; Koutli, Evangelia; Makris, Nikolaos; Kanakakis, Ioannis; Stamatelopoulos, Kimon

    2017-06-01

    Associations of endogenous androgens in menopause with blood pressure (BP) and indices of arterial stiffness are reported, but directional relationships are not clear. Structural equation modeling is a contemporary statistical method, which allows assessment of such relationships and improves pathway understanding. We recruited 411 consecutive apparently healthy postmenopausal women who underwent noninvasive vascular evaluation. This included pulse wave analysis (aortic pressures and arterial wave reflections [augmentation index]), measurement of aortic stiffness by pulse wave velocity (PWV), stiffness index (SI), and flow-mediated dilatation. A cumulative marker combining PWV and SI (combined local and aortic arterial stiffness [CAS]) was also assessed. Free androgen index (FAI) was calculated from circulating total testosterone and sex hormone-binding globulin. FAI was an independent determinant of systolic BP (SBP) (P = 0.032), SI (P = 0.042), and PWV (P = 0.027). Under structural equation modeling analysis, FAI was a direct predictor for PWV (beta = 0.149, P = 0.014), SI (beta = 0.154, P = 0.022), and CAS (beta = 0.193, P = 0.02), whereas SBP was a parallel mediator of androgen's vascular effects on PWV (beta = 0.280, P stiffness via flow-mediated dilatation was not established. FAI was not a determinant of augmentation index. In healthy postmenopausal women, FAI was directly associated with PWV, SI, and CAS. FAI also directly correlated with SBP, which in turn concurrently increased PWV and CAS. The directional correlations found herein, imply that endogenous androgens may be causally associated with indices of arterial stiffness both directly and indirectly. This hypothesis should be confirmed in further studies with causal design.

  2. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

    International Nuclear Information System (INIS)

    Menon, M.; Peegel, H.; Katta, V.

    1985-01-01

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

  3. CHARACTERISATION OF CELL-MEDIATED IMMUNE RESPONSE IN PIGS IN A CLINICAL CHALLENGE EXPERIMENT OF A VACCINE AGAINST MYCOPLASMA HYOSYNOVIAE

    DEFF Research Database (Denmark)

    Rasmussen, Josephine Skovgaard; Riber, Ulla; Lauritsen, Klara Tølbøll

    be due to increased systemic infection in the placebo group. Cell-mediated immune response was further characterised by four colour flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) before Mhs challenge (day -1) and at days 6 and 9 after challenge. IFN-γ producing cells were found...... to be CD4 and especially CD4CD8 double positive T-cells simultaneously expressing CD25. Interestingly, the proportion of CD4CD8 double positive T-cells within the total population of CD4 positive cells increased in the vaccine group after challenge, indicating that generation of specific T-cell memory had...

  4. Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

    DEFF Research Database (Denmark)

    Linde, Rasmus; Hasselbalch, Steen G.; Topp, Simon

    2006-01-01

    and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate......In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated...... that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions...

  5. APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

    Directory of Open Access Journals (Sweden)

    Hilla Fogel

    2014-06-01

    Full Text Available Accumulation of amyloid-β peptides (Aβ, the proteolytic products of the amyloid precursor protein (APP, induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease.

  6. Increasing Throughput: Results from a 42-Hospital Collaborative to Improve Emergency Department Flow.

    Science.gov (United States)

    Zocchi, Mark S; McClelland, Mark S; Pines, Jesse M

    2015-12-01

    An 18-month collaborative in 42 hospitals across 16 communities in the United States to improve emergency department (ED) flow was conducted from October 2010 through March 2012. Hospitals were invited to participate through the Aligning Forces for Quality (AF4Q) program. Each participating hospital identified one or more interventions to improve ED flow and submitted data on four measures of ED flow: discharged length of stay (LOS), admitted LOS, boarding time, and left without being seen (LWBS) rates. Participating hospitals also provided quarterly progress reports on challenges encountered and lessons learned. Univariate linear regression was used to assess the effectiveness of interventions at the hospital level, where an improvement was defined as a negative slope in one or more of the throughput indicators. Challenges and lessons learned were tabulated and described. A total of 172 interventions were implemented across the 42 hospitals. Two thirds (n = 28) demonstrated improvement on at least one measure of ED flow. Among hospitals demonstrating improvement, the average reduction in discharged LOS was 26 minutes (95% confidence interval [CI] 11 to 41); admitted LOS, 36.5 minutes (95% CI 20 to 53), boarding time, 20.9 minutes (95% CI 12 to 30), and LWBS seen rates decreased by 1.4 absolute percentage points (95% CI 0.2 to 2.7). Teams were frequently challenged by issues related to leadership, staff buy-in, and resource constraints. The majority of hospitals in this collaborative improved on one or more ED flow measures. Many challenges were shared across hospitals, demonstrating that successful approaches to ED flow improvement require certain fundamental elements, including engaged leadership and staff, and sufficient resources.

  7. Drivers of increased organic carbon concentrations in stream water following forest disturbance: Separating effects of changes in flow pathways and soil warming

    Science.gov (United States)

    Schelker, J.; Grabs, T.; Bishop, K.; Laudon, H.

    2013-12-01

    disturbance such as clear-cutting has been identified as an important factor for increasing dissolved organic carbon (DOC) concentrations in boreal streams. We used a long-term data set of soil temperature, soil moisture, shallow groundwater (GW) levels, and stream DOC concentrations from three boreal first-order streams to investigate mechanisms causing these increases. Clear-cutting was found to alter soil conditions with warmer and wetter soils during summer. The application of a riparian flow concentration integration model (RIM) explained a major part of variation in stream [DOC] arising from changing flow pathways in riparian soils during the pretreatment period (r2 = 0.4-0.7), but less well after the harvest. Model residuals were sensitive to changes in soil temperature. The linear regression models for the temperature dependence of [DOC] in soils were not different in the disturbed and undisturbed catchments, whereas a nonlinear response to soil moisture was found. Overall these results suggest that the increased DOC mobilization after forest disturbance is caused by (i) increased GW levels leading to increased water fluxes in shallow flow path in riparian soils and (ii) increased soil temperature increasing the DOC availability in soils during summer. These relationships indicate that the mechanisms of DOC mobilization after forest disturbance are not different to those of undisturbed catchments, but that catchment soils respond to the higher hydro-climatic variation observed after clear-cutting. This highlights the sensitivity of boreal streams to changes in the energy and water balance, which may be altered as a result of both land management and climate change.

  8. CTGF/CCN2 Postconditioning Increases Tolerance of Murine Hearts towards Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Kaasbøll, Ole Jørgen; Moe, Ingvild Tronstad; Ahmed, Mohammad Shakil; Stang, Espen; Hagelin, Else Marie Valbjørn; Attramadal, Håvard

    2016-01-01

    Previous studies of ischemia-reperfusion injury (IRI) in hearts from mice with cardiac-restricted overexpression of CCN2 have shown that CCN2 increases tolerance towards IRI. The objectives of this study were to investigate to what extent post-ischemic administration of recombinant human CCN2 (rhCCN2) would limit infarct size and improve functional recovery and what signaling pathways are involved. Isolated mice hearts were perfused ad modum Langendorff, subjected to no-flow, global ischemia, and subsequently, exposed to mammalian cell derived, full-length (38-40kDa) rhCCN2 (250 nM) or vehicle during the first 15 min of a 60 min reperfusion period. Post-ischemic administration of rhCCN2 resulted in attenuation of infarct size from 58 ± 4% to 34 ± 2% (p concentration-dependent increase of cardiac phospho-GSK3β (serine-9) contents. We demonstrate that post-ischemic administration of rhCCN2 increases the tolerance of ex vivo-perfused murine hearts to IRI. Mechanistically, this postconditioning effect of rhCCN2 appeared to be mediated by activation of the reperfusion injury salvage kinase pathway as demonstrated by sensitivity to PI3 kinase inhibition and increased CCN2-induced phosphorylation of GSK3β (Ser-9). Thus, the rationale for testing rhCCN2-mediated post-ischemic conditioning of the heart in more complex models is established.

  9. Effects of Flowing RBCs on Adhesion of a Circulating Tumor Cell in Microvessels

    Science.gov (United States)

    Xiao, L.L.; Liu, Y.; Chen, S.; Fu, B.M.

    2016-01-01

    Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cells (RBCs) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBCs aggregation was modelled by a Morse potential function based on depletion-mediated assumption and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of 15μm diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor-ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC. PMID:27738841

  10. GEOGRAPHICAL EDUCATION MEDIATIZATION AND MEDIASECURITY ISSUES

    Directory of Open Access Journals (Sweden)

    M. R. Arpentieva

    2017-01-01

    Full Text Available The article is devoted to the interaction of legal and moral development of media technologies in the context of geographical education. The article summarizes the experience of the theoretical analysis of mediatization in geographic education, the legal and moral aspects of the disorders and ways of their prevention and correction in the process of educational interaction between teacher and student, between student and teacher, mediated mediatechnologies. It is noted that geographical education in the modern world is education, which is closely associated with the use of media technologies. In other types of education the role of media technologies in improving the quality of education is less obvious, in the field of teaching and learning geography, it speaks very clearly. Therefore, the problems associated with its mediatization, are very important and their solution is particularly compelling. These issues are primarily associated with actively flowing social, economic, political and ideological crisis in many communities and countries of the Earth. Many of them as in the “mirror” are reflected in the sphere of high technologies, including media technologies. The article provides guidance and direction to the correction of violations at the individual and social levels.

  11. Exposure to cigarette smoke increases apoptosis in the rat gastric mucosa through a reactive oxygen species-mediated and p53-independent pathway.

    Science.gov (United States)

    Wang, H; Ma, L; Li, Y; Cho, C H

    2000-04-01

    Cigarette smoking is a major risk factor for gastric cancer and peptic ulcer. The aim of our study was to investigate the relationship between exposure to cigarette smoke and apoptosis in the rat gastric mucosa and the mechanism involved. Rats were exposed to different concentrations of cigarette smoke (0, 2, and 4%) once daily for a different number of 1 h periods (1, 3, 6, and 9 d). Apoptosis was identified by the terminal deoxy-transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method and caspase-3 activity. The mucosal xanthine oxidase (XO) activity and p53 level were also measured. The results showed that exposure to cigarette smoke produced a time- and concentration-dependent increase in apoptosis in the rat gastric mucosa that was accompanied by an increase in XO activity. The increased apoptosis and XO activity could be detected after even a single exposure. In contrast, the level of p53 was elevated only in the later stage of cigarette smoke exposure. The apoptotic effect could be blocked by pretreatment with an XO inhibitor (allopurinol, 20 mg/kg intraperitoneally) or a hydroxyl free radical scavenger (DMSO, 0.2%, 1 ml/kg intravenously). However, neither of these treatments had any effect on the p53 level of the mucosa. In summary, we conclude that exposure to cigarette smoke can increase apoptosis in the rat gastric mucosa through a reactive oxygen species- (ROS) mediated and a p53-independent pathway.

  12. Lack of dependence of 5-fluorodeoxyuridine-mediated radiosensitization on cytotoxicity

    International Nuclear Information System (INIS)

    Lawrence, T.S.; Davis, M.A.; Chang, E.Y.

    1995-01-01

    It has been proposed that fluoropyrimidine-mediated cytotoxicity and radiosensitization are closely correlated. We have shown that HT29 human colon cancer cells transfected with the E. coli dUTPase gene are resistant to 5-fluorodeoxyuridine (FdUrd)-mediated cytotoxicity, presumably through more effective elimination of dUTP. We used these cells to assess the association between radiosensitization and cytotoxicity produced by FdUrd. The radiation sensitivities of the clones expressing elevated dUTPase activity (dutE clones) were similar to those of untransfected HT29 cells or HT29 cells which has been transfected with only the expression vector for the E. coli gene (con clones). We found that FdUrd produced similar increases in radiation sensitivity regardless of dUTPase activity. Levels of dUTPase in the dutE clones remained elevated during the entire period of FdUrd exposure, demonstrating that the lack of difference between dutE and Con clones was not a reflection of down-regulation of dUTPase activity by FdUrd, Flow cytometry showed that all clones progressed past the G 1 /S-phase boundary and into early S phase during FdUrd treatment. These data suggest that the mechanisms of FdUrd-mediated cytotoxicity and radiosensitization are not closely linked. These findings, combined with our previous investigations, are consistent with the hypothesis that radiosensitization occurs in cells which progress past the G 1 /S-phase boundary in the presence of FdUrd. 24 refs., 2 figs., 2 tabs

  13. Neural control of blood flow during exercise in human metabolic syndrome.

    Science.gov (United States)

    Limberg, Jacqueline K; Morgan, Barbara J; Sebranek, Joshua J; Proctor, Lester T; Eldridge, Marlowe W; Schrage, William G

    2014-09-01

    α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P  0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  14. Glycocalyx Degradation Induces a Proinflammatory Phenotype and Increased Leukocyte Adhesion in Cultured Endothelial Cells under Flow.

    Directory of Open Access Journals (Sweden)

    Karli K McDonald

    Full Text Available Leukocyte adhesion to the endothelium is an early step in the pathogenesis of atherosclerosis. Effective adhesion requires the binding of leukocytes to their cognate receptors on the surface of endothelial cells. The glycocalyx covers the surface of endothelial cells and is important in the mechanotransduction of shear stress. This study aimed to identify the molecular mechanisms underlying the role of the glycocalyx in leukocyte adhesion under flow. We performed experiments using 3-D cell culture models, exposing human abdominal aortic endothelial cells to steady laminar shear stress (10 dynes/cm2 for 24 hours. We found that with the enzymatic degradation of the glycocalyx, endothelial cells developed a proinflammatory phenotype when exposed to uniform steady shear stress leading to an increase in leukocyte adhesion. Our results show an up-regulation of ICAM-1 with degradation compared to non-degraded controls (3-fold increase, p<0.05 and we attribute this effect to a de-regulation in NF-κB activity in response to flow. These results suggest that the glycocalyx is not solely a physical barrier to adhesion but rather plays an important role in governing the phenotype of endothelial cells, a key determinant in leukocyte adhesion. We provide evidence for how the destabilization of this structure may be an early and defining feature in the initiation of atherosclerosis.

  15. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Regional Organisations and International Mediation: The Effectiveness of Insider Mediators. ... During the last two decades of the twentieth century, the world witnessed an increasing number of regional conflict management efforts undertaken by regional inter-governmental organisations. There are therefore strong reasons ...

  16. The role of strain hardening in the transition from dislocation-mediated to frictional deformation of marbles within the Karakoram Fault Zone, NW India

    Science.gov (United States)

    Wallis, David; Lloyd, Geoffrey E.; Hansen, Lars N.

    2018-02-01

    The onset of frictional failure and potentially seismogenic deformation in carbonate rocks undergoing exhumation within fault zones depends on hardening processes that reduce the efficiency of aseismic dislocation-mediated deformation as temperature decreases. However, few techniques are available for quantitative analysis of dislocation slip system activity and hardening in natural tectonites. Electron backscatter diffraction maps of crystal orientations offer one such approach via determination of Schmid factors, if the palaeostress conditions can be inferred and the critical resolved shear stresses of slip systems are constrained. We analyse calcite marbles deformed in simple shear within the Karakoram Fault Zone, NW India, to quantify changes in slip system activity as the rocks cooled during exhumation. Microstructural evidence demonstrates that between ∼300 °C and 200-250 °C the dominant deformation mechanisms transitioned from dislocation-mediated flow to twinning and frictional failure. However, Schmid factor analysis, considering critical resolved shear stresses for yield of undeformed single crystals, indicates that the fraction of grains with sufficient resolved shear stress for glide apparently increased with decreasing temperature. Misorientation analysis and previous experimental data indicate that strain-dependent work hardening is responsible for this apparent inconsistency and promoted the transition from dislocation-mediated flow to frictional, and potentially seismogenic, deformation.

  17. Nitric oxide inhibits the bradykinin B2 receptor-mediated adrenomedullary catecholamine release but has no effect on adrenal blood flow response in vivo.

    Science.gov (United States)

    Bouallegue, Ali; Yamaguchi, Nobuharu

    2005-06-01

    The role of nitric oxide (NO) in bradykinin (BK)-induced adrenal catecholamine secretion still remains obscure. The present study was to investigate whether an inhibition of NO synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) would modulate BK-induced adrenal catecholamine secretion (ACS) and adrenal vasodilating response (AVR) in anesthetized dogs. Plasma catecholamine concentrations were determined with an HPLC coupled with an electrochemical detector. All drugs were locally administered to the left adrenal gland via intra-arterial infusion. BK dose-dependently increased both ACS and AVR. Hoe-140, a selective B(2) antagonist, significantly blocked the BK-induced increases in both ACS and AVR. In the presence of L-NAME, the BK-induced ACS was significantly enhanced, while the simultaneous AVR remained unaffected. These results suggest that the both BK-induced ACS and AVR are primarily mediated by B(2) receptors in the canine adrenal gland. Our results also suggest that the enhanced ACS in response to BK in the presence of L-NAME may have resulted from a specific inhibition of NO formation in the adrenal gland. It is concluded that the BK-induced NO may play an inhibitory role in the B(2)-receptor-mediated mechanisms regulating ACS, while it may not be implicated in the B(2)-receptor-mediated AVR under in vivo conditions.

  18. Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.

    Science.gov (United States)

    Chen, Huang-Hui; Chang, Hsin-Huei; Chang, Jang-Yang; Tang, Ya-Chu; Cheng, Yung-Chi; Lin, Li-Mei; Cheng, Shu-Ying; Huang, Chih-Hsiang; Sun, Man-Wu; Chen, Chiung-Tong; Kuo, Ching-Chuan

    2017-12-01

    Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches. The result demonstrated that silencing of NRF2 by RNA interference increased the sensitivity and treatment with NRF2 activator decreased the sensitivity of KB and KB-7D cells toward Top II poisons. Further, increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation activated NRF2 signaling in KB-7D cells. Moreover, increased binding of NRF2 to an ARE in the promoter of ATP-binding cassette subfamily C member 1 (ABCC1) directly contributed to Top II poison resistance. In addition, activation of NRF2 increased glutathione level and antioxidant capacity in KB-7D cells compared with that in KB cells; moreover, high glutathione level provided survival advantage to KB-7D cells. Our study is the first to show that aberrant NRF2 activation is via increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation, which increases the acquired resistance and promote the survival of Top II poison-resistant cancer cells. Importantly, NRF2 downstream effectors ABCC1 and glutathione directly contribute to acquired resistance and survival, respectively. These results suggest that blockade of NRF2 signaling may enhance therapeutic efficacy and reduce the survival of Top II poison-refractory tumors in clinical. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A century of changing flows: Forest management changed flow magnitudes and warming advanced the timing of flow in a southwestern US river.

    Directory of Open Access Journals (Sweden)

    Marcos D Robles

    Full Text Available The continued provision of water from rivers in the southwestern United States to downstream cities, natural communities and species is at risk due to higher temperatures and drought conditions in recent decades. Snowpack and snowfall levels have declined, snowmelt and peak spring flows are arriving earlier, and summer flows have declined. Concurrent to climate change and variation, a century of fire suppression has resulted in dramatic changes to forest conditions, and yet, few studies have focused on determining the degree to which changing forests have altered flows. In this study, we evaluated changes in flow, climate, and forest conditions in the Salt River in central Arizona from 1914-2012 to compare and evaluate the effects of changing forest conditions and temperatures on flows. After using linear regression models to remove the influence of precipitation and temperature, we estimated that annual flows declined by 8-29% from 1914-1963, coincident with a 2-fold increase in basal area, a 2-3-fold increase in canopy cover, and at least a 10-fold increase in forest density within ponderosa pine forests. Streamflow volumes declined by 37-56% in summer and fall months during this period. Declines in climate-adjusted flows reversed at mid-century when spring and annual flows increased by 10-31% from 1964-2012, perhaps due to more winter rainfall. Additionally, peak spring flows occurred about 12 days earlier in this period than in the previous period, coincident with winter and spring temperatures that increased by 1-2°C. While uncertainties remain, this study adds to the knowledge gained in other regions that forest change has had effects on flow that were on par with climate variability and, in the case of mid-century declines, well before the influence of anthropogenic warming. Current large-scale forest restoration projects hold some promise of recovering seasonal flows.

  20. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  1. Ultrasound-mediated vascular gene transfection by cavitation of endothelial-targeted cationic microbubbles.

    Science.gov (United States)

    Xie, Aris; Belcik, Todd; Qi, Yue; Morgan, Terry K; Champaneri, Shivam A; Taylor, Sarah; Davidson, Brian P; Zhao, Yan; Klibanov, Alexander L; Kuliszewski, Michael A; Leong-Poi, Howard; Ammi, Azzdine; Lindner, Jonathan R

    2012-12-01

    Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)-stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm(2)). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1-targeted microbubbles and by ultrasound molecular imaging of P-selectin-targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin-targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa

  2. Determination of Complement-Mediated Killing of Bacteria by Viability Staining and Bioluminescence

    OpenAIRE

    Virta, Marko; Lineri, Sanna; Kankaanpää, Pasi; Karp, Matti; Peltonen, Karita; Nuutila, Jari; Lilius, Esa-Matti

    1998-01-01

    Complement-mediated killing of bacteria was monitored by flow cytometric, luminometric, and conventional plate counting methods. A flow cytometric determination of bacterial viability was carried out by using dual staining with a LIVE/DEAD BacLight bacterial viability kit. In addition to the viable cell population, several other populations emerged in the fluorescence histogram, and there was a dramatic decrease in the total cell count in the light-scattering histogram in the course of the co...

  3. Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia

    Science.gov (United States)

    Baeyens, Nicolas; Larrivée, Bruno; Ola, Roxana; Hayward-Piatkowskyi, Brielle; Dubrac, Alexandre; Huang, Billy; Ross, Tyler D.; Coon, Brian G.; Min, Elizabeth; Tsarfati, Maya; Tong, Haibin; Eichmann, Anne

    2016-01-01

    Morphogenesis of the vascular system is strongly modulated by mechanical forces from blood flow. Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal-dominant disease in which arteriovenous malformations and telangiectasias accumulate with age. Most cases are linked to heterozygous mutations in Alk1 or Endoglin, receptors for bone morphogenetic proteins (BMPs) 9 and 10. Evidence suggests that a second hit results in clonal expansion of endothelial cells to form lesions with poor mural cell coverage that spontaneously rupture and bleed. We now report that fluid shear stress potentiates BMPs to activate Alk1 signaling, which correlates with enhanced association of Alk1 and endoglin. Alk1 is required for BMP9 and flow responses, whereas endoglin is only required for enhancement by flow. This pathway mediates both inhibition of endothelial proliferation and recruitment of mural cells; thus, its loss blocks flow-induced vascular stabilization. Identification of Alk1 signaling as a convergence point for flow and soluble ligands provides a molecular mechanism for development of HHT lesions. PMID:27646277

  4. Flow heterogeneity following global no-flow ischemia in isolated rabbit heart

    International Nuclear Information System (INIS)

    Marshall, Robert C.; Powers-Risius, Patricia; Reutter, Bryan W.; Schustz, Amy M.; Kuo, Chaincy; Huesman, Michelle K.; Huesman, Ronald H.

    2002-01-01

    The purpose of this study was to evaluate flow heterogeneity and impaired reflow during reperfusion following 60 min global no-flow ischemia in the isolated rabbit heart. Radiolabeled microspheres were used to measure relative flow in small left ventricular (LV) segments in five ischemia + reperfused hearts and in five non-ischemic controls. Although variable in the post-ischemic hearts, flow heterogeneity was increased relative to pre-ischemia for the whole LV (0.92 plus or minus 0.41 vs. 0.37 plus or minus 0.07, P < 0.05) as well as the subendocardium (Endo) and subepicardium (Epi) considered separately (endo: 1.28 plus or minus 0.74 vs. 0.30 plus or minus 0.09; epi: 0.69 plus or minus 0.22 vs. 0.38 plus or minus 0.08; P < 0.05 for both comparisons) during early reperfusion. There were also segments with abnormally reduced reflow. The number of segments with abnormally reduced reflow increased as flow heterogeneity increased. Abnormally reduced reflow indicates that regional ischemia can persist despite restoration of normal global flow. In addition, the relationship between regional and global flow is altered and venous outflow is derived from regions with continued perfusion and not the whole LV. These observations emphasize the need to quantify regional reflow during reperfusion following sustained no-flow ischemia in the isolated rabbit heart

  5. Flow heterogeneity following global no-flow ischemia in isolated rabbit heart

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Robert C.; Powers-Risius, Patricia; Reutter, Bryan W.; Schustz, Amy M.; Kuo, Chaincy; Huesman, Michelle K.; Huesman, Ronald H.

    2003-02-01

    The purpose of this study was to evaluate flow heterogeneity and impaired reflow during reperfusion following 60 min global no-flow ischemia in the isolated rabbit heart. Radiolabeled microspheres were used to measure relative flow in small left ventricular (LV) segments in five ischemia + reperfused hearts and in five non-ischemic controls. Although variable in the post-ischemic hearts, flow heterogeneity was increased relative to pre-ischemia for the whole LV (0.92 plus or minus 0.41 vs. 0.37 plus or minus 0.07, P < 0.05) as well as the subendocardium (Endo) and subepicardium (Epi) considered separately (endo: 1.28 plus or minus 0.74 vs. 0.30 plus or minus 0.09; epi: 0.69 plus or minus 0.22 vs. 0.38 plus or minus 0.08; P < 0.05 for both comparisons) during early reperfusion. There were also segments with abnormally reduced reflow. The number of segments with abnormally reduced reflow increased as flow heterogeneity increased. Abnormally reduced reflow indicates that regional ischemia can persist despite restoration of normal global flow. In addition, the relationship between regional and global flow is altered and venous outflow is derived from regions with continued perfusion and not the whole LV. These observations emphasize the need to quantify regional reflow during reperfusion following sustained no-flow ischemia in the isolated rabbit heart.

  6. Reactive Transport Modeling of Microbe-mediated Fe (II) Oxidation for Enhanced Oil Recovery

    Science.gov (United States)

    Surasani, V.; Li, L.

    2011-12-01

    Microbially Enhanced Oil Recovery (MEOR) aims to improve the recovery of entrapped heavy oil in depleted reservoirs using microbe-based technology. Reservoir ecosystems often contain diverse microbial communities those can interact with subsurface fluids and minerals through a network of nutrients and energy fluxes. Microbe-mediated reactions products include gases, biosurfactants, biopolymers those can alter the properties of oil and interfacial interactions between oil, brine, and rocks. In addition, the produced biomass and mineral precipitates can change the reservoir permeability profile and increase sweeping efficiency. Under subsurface conditions, the injection of nitrate and Fe (II) as the electron acceptor and donor allows bacteria to grow. The reaction products include minerals such as Fe(OH)3 and nitrogen containing gases. These reaction products can have large impact on oil and reservoir properties and can enhance the recovery of trapped oil. This work aims to understand the Fe(II) oxidation by nitrate under conditions relevant to MEOR. Reactive transport modeling is used to simulate the fluid flow, transport, and reactions involved in this process. Here we developed a complex reactive network for microbial mediated nitrate-dependent Fe (II) oxidation that involves both thermodynamic controlled aqueous reactions and kinetic controlled Fe (II) mineral reaction. Reactive transport modeling is used to understand and quantify the coupling between flow, transport, and reaction processes. Our results identify key parameter controls those are important for the alteration of permeability profile under field conditions.

  7. Solution-mediated phase transformation of haloperidol mesylate in the presence of sodium lauryl sulfate.

    Science.gov (United States)

    Greco, Kristyn; Bogner, Robin

    2011-09-01

    Forming a salt is a common way to increase the solubility of a poorly soluble compound. However, the solubility enhancement gained by salt formation may be lost due to solution-mediated phase transformation (SMPT) during dissolution. The SMPT of a salt can occur due to a supersaturated solution near the dissolving surface caused by pH or other solution conditions. In addition to changes in pH, surfactants are also known to affect SMPT. In this study, SMPT of a highly soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution experiments were performed using a flow-through dissolution apparatus with solutions containing various concentrations of SLS. Compacts of haloperidol mesylate were observed during dissolution in the flow-through apparatus using a stereomicroscope. Raman microscopy was used to characterize solids. The dissolution of haloperidol mesylate was significantly influenced by the addition of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol mesylate. In solutions containing concentrations of SLS above the critical micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate increased compared to below the CMC. The solids recovered from solubility experiments of haloperidol mesylate indicated that haloperidol free base precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy suggested a new form, perhaps the estolate salt. The addition of surfactant in solids that undergo solution-mediated phase transformation can add complexity to the dissolution profiles and conversion.

  8. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  9. Differential increases in blood flow velocity in the middle cerebral artery after tourniquet deflation during sevoflurane, isoflurane or propofol anaesthesia.

    Science.gov (United States)

    Kadoi, Y; Kawauchi, C H; Ide, M; Saito, S; Mizutani, A

    2009-07-01

    The purpose of this study was to examine the comparative effects of sevoflurane, isoflurane or propofol on cerebral blood flow velocity after tourniquet deflation during orthopaedic surgery. Thirty patients undergoing elective orthopaedic surgery were randomly divided into sevoflurane, isoflurane and propofol groups. Anaesthesia was maintained with sevoflurane, isoflurane or propofol infusion in 33% oxygen and 67% nitrous oxide, in whatever concentrations were necessary to keep bispectral index values between 45 and 50. Ventilatory rate or tidal volume was adjusted to target PaCO2 of 35 mmHg. A 2.0 MHz transcranial Doppler probe was attached to the patient's head at the temporal window and mean blood flow velocity in the middle cerebral artery was continuously measured. The extremity was exsanguinated with an Esmarch bandage and the pneumatic tourniquet was inflated to a pressure of 450 mmHg. Arterial blood pressure, heart rate, velocity in the middle cerebral artery and arterial blood gas analysis were measured every minute for 10 minutes after release of the tourniquet in all three groups. Velocity in the middle cerebral artery in the three groups increased for five minutes after tourniquet deflation. Because of the different cerebrovascular effects of the three agents, the degree of increase in flow velocity in the isoflurane group was greater than in the other two groups, the change in flow velocity in the propofol group being the lowest (at three minutes after deflation 40 +/- 7%, 32 +/- 6% and 28 +/- 10% in the isoflurane, sevoflurane and propofol groups respectively, P < 0.05).

  10. Gaseous slip flow analysis of a micromachined flow sensor for ultra small flow applications

    Science.gov (United States)

    Jang, Jaesung; Wereley, Steven T.

    2007-02-01

    The velocity slip of a fluid at a wall is one of the most typical phenomena in microscale gas flows. This paper presents a flow analysis considering the velocity slip in a capacitive micro gas flow sensor based on pressure difference measurements along a microchannel. The tangential momentum accommodation coefficient (TMAC) measurements of a particular channel wall in planar microchannels will be presented while the previous micro gas flow studies have been based on the same TMACs on both walls. The sensors consist of a pair of capacitive pressure sensors, inlet/outlet and a microchannel. The main microchannel is 128.0 µm wide, 4.64 µm deep and 5680 µm long, and operated under nearly atmospheric conditions where the outlet Knudsen number is 0.0137. The sensor was fabricated using silicon wet etching, ultrasonic drilling, deep reactive ion etching (DRIE) and anodic bonding. The capacitance change of the sensor and the mass flow rate of nitrogen were measured as the inlet-to-outlet pressure ratio was varied from 1.00 to 1.24. The measured maximum mass flow rate was 3.86 × 10-10 kg s-1 (0.019 sccm) at the highest pressure ratio tested. As the pressure difference increased, both the capacitance of the differential pressure sensor and the flow rate through the main microchannel increased. The laminar friction constant f sdot Re, an important consideration in sensor design, varied from the incompressible no-slip case and the mass sensitivity and resolution of this sensor were discussed. Using the current slip flow formulae, a microchannel with much smaller mass flow rates can be designed at the same pressure ratios.

  11. The role of zonal flows in disc gravito-turbulence

    Science.gov (United States)

    Vanon, R.

    2018-04-01

    The work presented here focuses on the role of zonal flows in the self-sustenance of gravito-turbulence in accretion discs. The numerical analysis is conducted using a bespoke pseudo-spectral code in fully compressible, non-linear conditions. The disc in question, which is modelled using the shearing sheet approximation, is assumed to be self-gravitating, viscous, and thermally diffusive; a constant cooling timescale is also considered. Zonal flows are found to emerge at the onset of gravito-turbulence and they remain closely linked to the turbulent state. A cycle of zonal flow formation and destruction is established, mediated by a slow mode instability (which allows zonal flows to grow) and a non-axisymmetric instability (which disrupts the zonal flow), which is found to repeat numerous times. It is in fact the disruptive action of the non-axisymmetric instability to form new leading and trailing shearing waves, allowing energy to be extracted from the background flow and ensuring the self-sustenance of the gravito-turbulent regime.

  12. The role of zonal flows in disc gravito-turbulence

    Science.gov (United States)

    Vanon, R.

    2018-07-01

    The work presented here focuses on the role of zonal flows in the self-sustenance of gravito-turbulence in accretion discs. The numerical analysis is conducted using a bespoke pseudo-spectral code in fully compressible, non-linear conditions. The disc in question, which is modelled using the shearing sheet approximation, is assumed to be self-gravitating, viscous, and thermally diffusive; a constant cooling time-scale is also considered. Zonal flows are found to emerge at the onset of gravito-turbulence and they remain closely linked to the turbulent state. A cycle of zonal flow formation and destruction is established, mediated by a slow mode instability (which allows zonal flows to grow) and a non-axisymmetric instability (which disrupts the zonal flow), which is found to repeat numerous times. It is in fact the disruptive action of the non-axisymmetric instability to form new leading and trailing shearing waves, allowing energy to be extracted from the background flow and ensuring the self-sustenance of the gravito-turbulent regime.

  13. Saline-induced natriuresis and renal blood flow in conscious dogs: effects of sodium infusion rate and concentration

    DEFF Research Database (Denmark)

    Sandgaard, N C F; Andersen, J L; Holstein-Rathlou, N-H

    2005-01-01

    AIM: This study focused on static and dynamic changes in total renal blood flow (RBF) during volume expansion and tested whether a change in RBF characteristics is a necessary effector mechanism in saline-induced natriuresis. METHODS: The aortic flow subtraction technique was used to measure RBF...... continuously. Identical amounts of NaCl (2.4 mmol kg(-1)) were given as slow isotonic (Iso, 120 min), slow hypertonic (Hyper, 120 min), and rapid isotonic loads (IsoRapid, 30 min). RESULTS: During Iso and IsoRapid, arterial blood pressure increased slightly (6-7 mmHg), and during Hyper it remained unchanged...... saline loading simulating daily sodium intake, the rate of sodium excretion may increase 10-20-fold without any change in mean arterial blood pressure or in RBF. Regulatory responses to changes in total body NaCl levels appears, therefore, to be mediated primarily by neurohumoral mechanisms and may occur...

  14. Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.

    Science.gov (United States)

    Bailey, Damian M; Rasmussen, Peter; Overgaard, Morten; Evans, Kevin A; Bohm, Aske M; Seifert, Thomas; Brassard, Patrice; Zaar, Morten; Nielsen, Henning B; Raven, Peter B; Secher, Niels H

    2017-01-10

    The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O 2 tension and blood flow. Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O 2 ) and hypoxic (10% O 2 ) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (Pflow during exercise (Pvenous; Parterial; P0.05). These findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation. © 2016 American Heart Association, Inc.

  15. Lipofuscin-mediated photic stress inhibits phagocytic activity of ARPE-19 cells; effect of donors' age and antioxidants.

    Science.gov (United States)

    Olchawa, Magdalena M; Furso, Justyna A; Szewczyk, Grzegorz M; Sarna, Tadeusz J

    2017-10-01

    The risk of chronic oxidative stress in the retinal pigment epithelium (RPE) increases with age due to accumulation of the photoreactive age pigment lipofuscin (LFG). Here, we asked whether sublethal and weakly lethal photic stress, induced by irradiation of ARPE-19 cells containing phagocytised LFG, affected the cell specific phagocytic activity, which is critically important for proper functioning and survival of the retina, and if natural antioxidants could modify the observed outcomes. ARPE-19 cells preloaded with LFG isolated from human donors of different age or containing LFG enriched with zeaxanthin and α-tocopherol (LFG-A), were irradiated with blue light. Phagocytosis of fluorescein-5-isothiocyanate (FITC)-labelled photoreceptor outer segments was determined by flow cytometry. Photoreactivity of LFG and LFG-A was analysed by measuring photoconsumption of oxygen and photogeneration of singlet oxygen mediated by the granules. LFG-mediated photic stress in ARPE-19 cells induced significant inhibition of their specific phagocytosis. The inhibitory effect increased with age of LFG donors and was reduced by enrichment of the granules with antioxidants. Oxygen consumption and generation of singlet oxygen induced by the photoexcited LFG increased with donor's age and was partially quenched by antioxidants. Although the phototoxic potential of lipofuscin increased with age, natural antioxidants reduced photoreactivity of LFG and their efficiency to induce oxidative stress. This study has demonstrated, for the first time, that mild oxidative stress, mediated by the age pigment lipofuscin, impairs specific phagocytic activity of RPE, and that natural antioxidants can protect this important cellular function by reducing lipofuscin photoreactivity.

  16. Counterbalancing hydrodynamic sample distortion effects increases resolution of free-flow zone electrophoresis.

    Science.gov (United States)

    Weber, G; Bauer, J

    1998-06-01

    On fractionation of highly heterogeneous protein mixtures, optimal resolution was achieved by forcing proteins to migrate through a preestablished pH gradient, until they entered a medium with a pH similar but not equal to their pIs. For this purpose, up to seven different media were pumped through the electrophoresis chamber so that they were flowing adjacently to each other, forming a pH gradient declining stepwise from the cathode to the anode. This gradient had a sufficiently strong band-focusing effect to counterbalance sample distortion effects of the flowing medium as proteins approached their isoelectric medium closer than 0.5 pH units. Continuous free-flow zone electrophoresis (FFZE) with high throughput capability was applicable if proteins did not precipitate or aggregate in these media. If components of heterogeneous protein mixtures had already started to precipitate or aggregate, in a medium with a pH exceeding their pI by more than 0.5 pH units, the application of interval modus and media forming flat pH gradients appeared advantageous.

  17. Systems and methods for rebalancing redox flow battery electrolytes

    Science.gov (United States)

    Pham, Ai Quoc; Chang, On Kok

    2015-03-17

    Various methods of rebalancing electrolytes in a redox flow battery system include various systems using a catalyzed hydrogen rebalance cell configured to minimize the risk of dissolved catalyst negatively affecting flow battery performance. Some systems described herein reduce the chance of catalyst contamination of RFB electrolytes by employing a mediator solution to eliminate direct contact between the catalyzed membrane and the RFB electrolyte. Other methods use a rebalance cell chemistry that maintains the catalyzed electrode at a potential low enough to prevent the catalyst from dissolving.

  18. Atomic Force Microscope Mediated Chromatography

    Science.gov (United States)

    Anderson, Mark S.

    2013-01-01

    The atomic force microscope (AFM) is used to inject a sample, provide shear-driven liquid flow over a functionalized substrate, and detect separated components. This is demonstrated using lipophilic dyes and normal phase chromatography. A significant reduction in both size and separation time scales is achieved with a 25-micron-length column scale, and one-second separation times. The approach has general applications to trace chemical and microfluidic analysis. The AFM is now a common tool for ultra-microscopy and nanotechnology. It has also been demonstrated to provide a number of microfluidic functions necessary for miniaturized chromatography. These include injection of sub-femtoliter samples, fluidic switching, and sheardriven pumping. The AFM probe tip can be used to selectively remove surface layers for subsequent microchemical analysis using infrared and tip-enhanced Raman spectroscopy. With its ability to image individual atoms, the AFM is a remarkably sensitive detector that can be used to detect separated components. These diverse functional components of microfluidic manipulation have been combined in this work to demonstrate AFM mediated chromatography. AFM mediated chromatography uses channel-less, shear-driven pumping. This is demonstrated with a thin, aluminum oxide substrate and a non-polar solvent system to separate a mixture of lipophilic dyes. In conventional chromatographic terms, this is analogous to thin-layer chromatography using normal phase alumina substrate with sheardriven pumping provided by the AFM tip-cantilever mechanism. The AFM detection of separated components is accomplished by exploiting the variation in the localized friction of the separated components. The AFM tip-cantilever provides the mechanism for producing shear-induced flows and rapid pumping. Shear-driven chromatography (SDC) is a relatively new concept that overcomes the speed and miniaturization limitations of conventional liquid chromatography. SDC is based on a

  19. Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus.

    Science.gov (United States)

    Padilla, Jaume; Johnson, Blair D; Newcomer, Sean C; Wilhite, Daniel P; Mickleborough, Timothy D; Fly, Alyce D; Mather, Kieren J; Wallace, Janet P

    2008-09-04

    Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability. Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy, physically active young adults (25.3 +/- 0. 6 yrs; 10 men, 10 women) by manipulating forearm cuff occlusion duration: 1, 2, 3, 4, and 5 min, in a randomized order. A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit. The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry (NIRS). Brachial artery diameters and velocities were obtained via high-resolution ultrasound. The SSAUC was individually calculated for the duration of time-to-peak dilation. One-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia (volume and peak), hyperemic shear stress, and peak FMD responses (all p index of endothelial function.

  20. Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability : A PET study

    NARCIS (Netherlands)

    Slart, Riemer H. J. A.; Agool, Ali; van Veldhuisen, Dirk J.; Dierckx, Rudi A.; Bax, Jeroen J.

    SPECT with Tc-99m-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasoclilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on

  1. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa.

    Directory of Open Access Journals (Sweden)

    Lewis H Ziska

    Full Text Available Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO(2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO(2 from an early 20(th century concentration (300 µmol mol(-1 to current (400 µmol mol(-1 and projected, mid-21(st century (600 µmol mol(-1 values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol(-1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO(2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO(2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems.

  2. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa).

    Science.gov (United States)

    Ziska, Lewis H; Gealy, David R; Tomecek, Martha B; Jackson, Aaron K; Black, Howard L

    2012-01-01

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO(2) between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO(2) from an early 20(th) century concentration (300 µmol mol(-1)) to current (400 µmol mol(-1)) and projected, mid-21(st) century (600 µmol mol(-1)) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol(-1). The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO(2) also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO(2) could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems.

  3. Usefulness of DC power flow for active power flow analysis with flow controlling devices

    NARCIS (Netherlands)

    Van Hertem, D.; Verboomen, J.; Purchala, K.; Belmans, R.; Kling, W.L.

    2006-01-01

    DC power flow is a commonly used tool for contingency analysis. Recently, due to its simplicity and robustness, it also becomes increasingly used for the real-time dispatch and techno-economic analysis of power systems. It is a simplification of a full power flow looking only at active power.

  4. Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging

    Science.gov (United States)

    Gordish, Kevin L.

    2014-01-01

    Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min−1·gram of kidney weight−1 (gkw); n = 8; P resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min−1·gkw−1; n = 10; P resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min−1·gkw−1; n = 7; P resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min−1·gkw−1; n = 7; P Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products. PMID:24431202

  5. Mobile Exercise Apps and Increased Leisure Time Exercise Activity: A Moderated Mediation Analysis of the Role of Self-Efficacy and Barriers

    Science.gov (United States)

    Rosen, Zohn; Spierer, David; Weinberger-Litman, Sarah; Goldschein, Akiva; Robinson, Jonathan

    2015-01-01

    that this association was mediated by exercise levels and self-efficacy. That relationship was also moderated by perceived barriers to exercise. Multiple serial mediation models were tested, which revealed that the association between app use and BMI is mediated by increased self-efficacy and increased exercise. Conclusions Exercise app users are more likely to exercise during their leisure time, compared to those who do not use exercise apps, essentially fulfilling the role that many of these apps were designed to accomplish. Data also suggest that one way that exercise apps may increase exercise levels and health outcomes such as BMI is by making it easier for users to overcome barriers to exercise, leading to increased self-efficacy. We discuss ways of improving the effectiveness of apps by incorporating theory-driven approaches. We conclude that exercise apps can be viewed as intervention delivery systems consisting of features that help users overcome specific barriers. PMID:26276227

  6. Mobile Exercise Apps and Increased Leisure Time Exercise Activity: A Moderated Mediation Analysis of the Role of Self-Efficacy and Barriers.

    Science.gov (United States)

    Litman, Leib; Rosen, Zohn; Spierer, David; Weinberger-Litman, Sarah; Goldschein, Akiva; Robinson, Jonathan

    2015-08-14

    There are currently over 1000 exercise apps for mobile devices on the market. These apps employ a range of features, from tracking exercise activity to providing motivational messages. However, virtually nothing is known about whether exercise apps improve exercise levels and health outcomes and, if so, the mechanisms of these effects. Our aim was to examine whether the use of exercise apps is associated with increased levels of exercise and improved health outcomes. We also develop a framework within which to understand how exercise apps may affect health and test multiple models of possible mechanisms of action and boundary conditions of these relationships. Within this framework, app use may increase physical activity by influencing variables such as self-efficacy and may help to overcome exercise barriers, leading to improved health outcomes such as lower body mass index (BMI). In this study, 726 participants with one of three backgrounds were surveyed about their use of exercise apps and health: (1) those who never used exercise apps, (2) those who used exercise apps but discontinued use, and (3) those who are currently using exercise apps. Participants were asked about their long-term levels of exercise and about their levels of exercise during the previous week with the International Physical Activity Questionnaire (IPAQ). Nearly three-quarters of current app users reported being more active compared to under half of non-users and past users. The IPAQ showed that current users had higher total leisure time metabolic equivalent of task (MET) expenditures (1169 METs), including walking and vigorous exercise, compared to those who stopped using their apps (612 METs) or who never used apps (577 METs). Importantly, physical activity levels in domains other than leisure time activity were similar across the groups. The results also showed that current users had lower BMI (25.16) than past users (26.8) and non-users (26.9) and that this association was mediated by

  7. Caffeine-mediated release of alpha-radiation-induced G2 arrest increases the yield of chromosome aberrations

    International Nuclear Information System (INIS)

    Luecke-Huhle, C.; Hieber, L.; Wegner, R.D.

    1983-01-01

    Severe and partly irreversible G2 arrest caused by americium-241 alpha-particles in Chinese hamster V79 cells acted as a competing process to the yield of detectable aberrant mitoses at metaphase. With increasing dose of alpha-radiation an increasing fraction of cells was irreversibly arrested in G2 with the consequence of interphase death before the first post-irradiation mitosis. This irreversible G2 arrest (demonstrated by flow cytofluorometry and mitotic indices) could be overcome by adding caffeine 8 hours after irradiation, the time point of maximum G2 arrest (80-90 per cent of all cells). Within 3.5 hours the number of aberrant mitoses increased by this treatment from 54 to 96 per cent and from 65 to 99.9 per cent for doses of 1.75 and 4.38 Gy of alpha-particles, respectively. The aberration frequency per mitotic cell, scored as chromatid and isochromatid breaks, rings, interchanges and dicentrics increased by a factor of about 3 after releasing G2 arrested cells. The frequency distribution of aberrations per cell revealed that, after 4.38 Gy, 58 per cent of the formerly G2-arrested cells had more than five aberrations per cell compared to only 8 per cent without the interaction of caffeine. (author)

  8. Pulmonary venous flow index as a predictor of pulmonary vascular resistance variability in congenital heart disease with increased pulmonary flow: a comparative study before and after oxygen inhalation.

    Science.gov (United States)

    Rivera, Ivan Romero; Mendonça, Maria Alayde; Andrade, José Lázaro; Moises, Valdir; Campos, Orlando; Silva, Célia Camelo; Carvalho, Antonio Carlos

    2013-09-01

    There is no definitive and reliable echocardiographic method for estimating the pulmonary vascular resistance (PVR) to differentiate persistent vascular disease from dynamic pulmonary hypertension. The aim of this study was to analyze the relationship between the pulmonary venous blood flow velocity-time integral (VTIpv) and PVR. Eighteen patients (10 females; 4 months to 22 years of age) with congenital heart disease and left to right shunt were studied. They underwent complete cardiac catheterization, including measurements of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous left inferior pulmonary venous flow VTIpv was obtained by Doppler echocardiography. The PVR decreased significantly from 5.0 ± 2.6 W to 2.8 ± 2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 ± 1.4 to 4.9 ± 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6 ± 4.7 cm to 28.1 ± 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively). Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy of 83%, a positive predictive value of 92% and a negative predictive value of 60%. The VTIpv correlated well with the PVR. The measurement of this index before and after oxygen inhalation may become a useful noninvasive test for differentiating persistent vascular disease from dynamic and flow-related pulmonary hypertension. © 2013, Wiley Periodicals, Inc.

  9. Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor {gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunjung; Shin, Soyoung; Lee, Jeeyoung; Lee, So Jung; Kim, Jinkyoung; Yoon, Doyoung; Kim, Yangmee [Konkuk Univ., Seoul (Korea, Republic of); Woo, Eunrhan [Chosun Univ., Gwangju (Korea, Republic of)

    2012-07-15

    Human peroxisomes proliferate-activated receptor gamma (hPPAR{gamma}) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPAR{gamma} and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPAR{gamma} expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPAR{gamma} in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPAR{gamma} activation.

  10. Parental Mediation in the Digital Era: Increasing Children's Critical Thinking May Help Decrease Positive Attitudes toward Alcohol.

    Science.gov (United States)

    Radanielina Hita, Marie Louise; Kareklas, Ioannis; Pinkleton, Bruce

    2018-01-01

    We demonstrate in our research that discussion-based parental mediation may successfully decrease the negative effects that youth's engagement with alcohol brands on social media may have on attitudes toward alcohol through its effects on critical thinking. A clear pattern was found with positive mediation leading to unhealthy outcomes and negative mediation predicting healthier behaviors. Youth whose parents critiqued media messages reported more critical thinking skills, which predicted less interaction with alcohol brands on social media and fewer expectancies toward alcohol. On the other hand, youth whose parents endorsed media portrayals of drinking reported fewer critical thinking skills and were thus more likely to interact with alcohol brands on social media. Including a media literacy component in alcohol education that target parental strategies and that are conducive to discussion may lead to beneficial health outcomes in the digital era.

  11. Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study.

    Science.gov (United States)

    Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

    2012-08-17

    Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a deswelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell edema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2), and extraction (RO2Ex) in early, ischemic AKI after cardiac surgery. Eleven patients with AKI were studied during propofol sedation and mechanical ventilation 2 to 6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intraaortic balloon pump (36%). Systemic hemodynamics were measured with a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF × (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol, 225 mg/kg, was given, followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods. Mannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P renal vascular resistance (P renal FF. Mannitol treatment of postoperative AKI

  12. The effect of chronic seaweed subsidies on herbivory: plant-mediated fertilization pathway overshadows lizard-mediated predator pathways.

    Science.gov (United States)

    Piovia-Scott, Jonah; Spiller, David A; Takimoto, Gaku; Yang, Louie H; Wright, Amber N; Schoener, Thomas W

    2013-08-01

    Flows of energy and materials link ecosystems worldwide and have important consequences for the structure of ecological communities. While these resource subsidies typically enter recipient food webs through multiple channels, most previous studies focussed on a single pathway of resource input. We used path analysis to evaluate multiple pathways connecting chronic marine resource inputs (in the form of seaweed deposits) and herbivory in a shoreline terrestrial ecosystem. We found statistical support for a fertilization effect (seaweed increased foliar nitrogen content, leading to greater herbivory) and a lizard numerical response effect (seaweed increased lizard densities, leading to reduced herbivory), but not for a lizard diet-shift effect (seaweed increased the proportion of marine-derived prey in lizard diets, but lizard diet was not strongly associated with herbivory). Greater seaweed abundance was associated with greater herbivory, and the fertilization effect was larger than the combined lizard effects. Thus, the bottom-up, plant-mediated effect of fertilization on herbivory overshadowed the top-down effects of lizard predators. These results, from unmanipulated shoreline plots with persistent differences in chronic seaweed deposition, differ from those of a previous experimental study of the short-term effects of a pulse of seaweed deposition: while the increase in herbivory in response to chronic seaweed deposition was due to the fertilization effect, the short-term increase in herbivory in response to a pulse of seaweed deposition was due to the lizard diet-shift effect. This contrast highlights the importance of the temporal pattern of resource inputs in determining the mechanism of community response to resource subsidies.

  13. Response of Xylella fastidiosa to zinc: decreased culturability, increased exopolysaccharide production, and formation of resilient biofilms under flow conditions.

    Science.gov (United States)

    Navarrete, Fernando; De La Fuente, Leonardo

    2014-02-01

    The bacterial plant pathogen Xylella fastidiosa produces biofilm that accumulates in the host xylem vessels, affecting disease development in various crops and bacterial acquisition by insect vectors. Biofilms are sensitive to the chemical composition of the environment, and mineral elements being transported in the xylem are of special interest for this pathosystem. Here, X. fastidiosa liquid cultures were supplemented with zinc and compared with nonamended cultures to determine the effects of Zn on growth, biofilm, and exopolysaccharide (EPS) production under batch and flow culture conditions. The results show that Zn reduces growth and biofilm production under both conditions. However, in microfluidic chambers under liquid flow and with constant bacterial supplementation (closer to conditions inside the host), a dramatic increase in biofilm aggregates was seen in the Zn-amended medium. Biofilms formed under these conditions were strongly attached to surfaces and were not removed by medium flow. This phenomenon was correlated with increased EPS production in stationary-phase cells grown under high Zn concentrations. Zn did not cause greater adhesion to surfaces by individual cells. Additionally, viability analyses suggest that X. fastidiosa may be able to enter the viable but nonculturable state in vitro, and Zn can hasten the onset of this state. Together, these findings suggest that Zn can act as a stress factor with pleiotropic effects on X. fastidiosa and indicate that, although Zn could be used as a bactericide treatment, it could trigger the undesired effect of stronger biofilm formation upon reinoculation events.

  14. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  15. Effect of gas temperature on flow rate characteristics of an averaging pitot tube type flow meter

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung Hwa; Lee, Su Ryong; Lee, Choong Hoon [Seoul National University of Science and Technology, Seoul (Korea, Republic of)

    2015-01-15

    The flow rate characteristics passing through an averaging Pitot tube (APT) while constantly controlling the flow temperature were studied through experiments and CFD simulations. At controlled temperatures of 25, 50, 75, and 100 .deg .C, the flow characteristics, in this case the upstream, downstream and static pressure at the APT flow meter probe, were measured as the flow rate was increased. The flow rate through the APT flow meter was represented using the H-parameter (hydraulic height) obtained by a combination of the differential pressure and the air density measured at the APT flow meter probe. Four types of H-parameters were defined depending on the specific combination. The flow rate and the upstream, downstream and static pressures measured at the APT flow meter while changing the H-parameters were simulated by means of CFD. The flow rate curves showed different features depending on which type of H-parameter was used. When using the constant air density value in a standard state to calculate the H-parameters, the flow rate increased linearly with the H-parameter and the slope of the flow rate curve according to the H-parameter increased as the controlled target air temperature was increased. When using different air density levels corresponding to each target air temperature to calculate the H-parameter, the slope of the flow rate curve according to the H-parameter was constant and the flow rate curve could be represented by a single line. The CFD simulation results were in good agreement with the experimental results. The CFD simulations were performed while increasing the air temperature to 1200 K. The CFD simulation results for high air temperatures were similar to those at the low temperature ranging from 25 to 100 .deg. C.

  16. Effect of gas temperature on flow rate characteristics of an averaging pitot tube type flow meter

    International Nuclear Information System (INIS)

    Yeo, Seung Hwa; Lee, Su Ryong; Lee, Choong Hoon

    2015-01-01

    The flow rate characteristics passing through an averaging Pitot tube (APT) while constantly controlling the flow temperature were studied through experiments and CFD simulations. At controlled temperatures of 25, 50, 75, and 100 .deg .C, the flow characteristics, in this case the upstream, downstream and static pressure at the APT flow meter probe, were measured as the flow rate was increased. The flow rate through the APT flow meter was represented using the H-parameter (hydraulic height) obtained by a combination of the differential pressure and the air density measured at the APT flow meter probe. Four types of H-parameters were defined depending on the specific combination. The flow rate and the upstream, downstream and static pressures measured at the APT flow meter while changing the H-parameters were simulated by means of CFD. The flow rate curves showed different features depending on which type of H-parameter was used. When using the constant air density value in a standard state to calculate the H-parameters, the flow rate increased linearly with the H-parameter and the slope of the flow rate curve according to the H-parameter increased as the controlled target air temperature was increased. When using different air density levels corresponding to each target air temperature to calculate the H-parameter, the slope of the flow rate curve according to the H-parameter was constant and the flow rate curve could be represented by a single line. The CFD simulation results were in good agreement with the experimental results. The CFD simulations were performed while increasing the air temperature to 1200 K. The CFD simulation results for high air temperatures were similar to those at the low temperature ranging from 25 to 100 .deg. C.

  17. The mechanism by which nonlinearity sustains turbulence in plane Couette flow

    Science.gov (United States)

    Nikolaidis, M.-A.; Farrell, B. F.; Ioannou, P. J.

    2018-04-01

    Turbulence in wall-bounded shear flow results from a synergistic interaction between linear non-normality and nonlinearity in which non-normal growth of a subset of perturbations configured to transfer energy from the externally forced component of the turbulent state to the perturbation component maintains the perturbation energy, while the subset of energy-transferring perturbations is replenished by nonlinearity. Although it is accepted that both linear non-normality mediated energy transfer from the forced component of the mean flow and nonlinear interactions among perturbations are required to maintain the turbulent state, the detailed physical mechanism by which these processes interact in maintaining turbulence has not been determined. In this work a statistical state dynamics based analysis is performed on turbulent Couette flow at R = 600 and a comparison to DNS is used to demonstrate that the perturbation component in Couette flow turbulence is replenished by a non-normality mediated parametric growth process in which the fluctuating streamwise mean flow has been adjusted to marginal Lyapunov stability. It is further shown that the alternative mechanism in which the subspace of non-normally growing perturbations is maintained directly by perturbation-perturbation nonlinearity does not contribute to maintaining the turbulent state. This work identifies parametric interaction between the fluctuating streamwise mean flow and the streamwise varying perturbations to be the mechanism of the nonlinear interaction maintaining the perturbation component of the turbulent state, and identifies the associated Lyapunov vectors with positive energetics as the structures of the perturbation subspace supporting the turbulence.

  18. Application of a Heat- and Steam-Generating Sheet Increases Peripheral Blood Flow and Induces Parasympathetic Predominance

    Directory of Open Access Journals (Sweden)

    Yoshinao Nagashima

    2011-01-01

    Full Text Available To promote the practical application of a Japanese traditional medical treatment, such as hot compresses, we developed a plaster-type warming device consisting of a heat- and steam-generating sheet (HSG sheet. First, we tested its effects when applied to the anterior abdominal wall or lumbar region of women complaining of a tendency towards constipation. Application of the sheet to either region produced a feeling of comfort in the abdomen, as assessed by a survey of the subjects. The significant increases in the total hemoglobin observed in these regions suggested an increase in peripheral blood flow, and significant increases in the HF component on ECG and in the amplitude of gastric motility suggested parasympathetic predominance. We concluded that application of the HSG sheet improves the peripheral hemodynamics and autonomic regulation, induces a feeling of comfort in the abdomen, and provides a beneficial environment for the improvement of gastrointestinal movements.

  19. Liquid-Flow Controller With Trickle Preflow

    Science.gov (United States)

    Cox, George B., Jr.

    1990-01-01

    Liquid-flow controller allows pressure in liquid to increase steeply with flow as flow starts, then provides more-gradual nearly linear rise of pressure with flow as flow and pressure increase beyond preset breakpoint. Controller alternative version of mechanism described in "Liquid-Flow Controller Responds To Pressure" (MFS-28329) and "Liquid-Flow Controller With Preset Break Pressure" (MFS-28330). Material cut out of cone at tip of pintle. Liquid always passes from shell, albeit at low rate. When pressure in shell great enough to force orifice away from pintle, liquid flows at greater rate.

  20. Experimental study of the influence of flow passage subtle variation on mixed-flow pump performance

    Science.gov (United States)

    Bing, Hao; Cao, Shuliang

    2014-05-01

    In the mixed-flow pump design, the shape of the flow passage can directly affect the flow capacity and the internal flow, thus influencing hydraulic performance, cavitation performance and operation stability of the mixed-flow pump. However, there is currently a lack of experimental research on the influence mechanism. Therefore, in order to analyze the effects of subtle variations of the flow passage on the mixed-flow pump performance, the frustum cone surface of the end part of inlet contraction flow passage of the mixed-flow pump is processed into a cylindrical surface and a test rig is built to carry out the hydraulic performance experiment. In this experiment, parameters, such as the head, the efficiency, and the shaft power, are measured, and the pressure fluctuation and the noise signal are also collected. The research results suggest that after processing the inlet flow passage, the head of the mixed-flow pump significantly goes down; the best efficiency of the mixed-flow pump drops by approximately 1.5%, the efficiency decreases more significantly under the large flow rate; the shaft power slightly increases under the large flow rate, slightly decreases under the small flow rate. In addition, the pressure fluctuation amplitudes on both the impeller inlet and the diffuser outlet increase significantly with more drastic pressure fluctuations and significantly lower stability of the internal flow of the mixed-flow pump. At the same time, the noise dramatically increases. Overall speaking, the subtle variation of the inlet flow passage leads to a significant change of the mixed-flow pump performance, thus suggesting a special attention to the optimization of flow passage. This paper investigates the influence of the flow passage variation on the mixed-flow pump performance by experiment, which will benefit the optimal design of the flow passage of the mixed-flow pump.

  1. The functionalized amino acid (S-Lacosamide subverts CRMP2-mediated tubulin polymerization to prevent constitutive and activity-dependent increase in neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Sarah M Wilson

    2014-07-01

    Full Text Available Activity-dependent neurite outgrowth is a highly complex, regulated process with important implications for neuronal circuit remodeling in development as well as in seizure-induced sprouting in epilepsy. Recent work has linked outgrowth to collapsin response mediator protein 2 (CRMP2, an intracellular phosphoprotein originally identified as axon guidance and growth cone collapse protein. The neurite outgrowth promoting function of CRMP2 is regulated by its phosphorylation state. In this study, depolarization (potassium chloride-driven activity increased the level of active CRMP2 by decreasing its phosphorylation by GSK3β via a reduction in priming by Cdk5. To determine the contribution of CRMP2 in activity-driven neurite outgrowth, we screened a limited set of compounds for their ability to reduce neurite outgrowth but not modify voltage-gated sodium channel (VGSC biophysical properties. This led to the identification of (S-lacosamide ((S-LCM, a stereoisomer of the clinically used antiepileptic drug (R-LCM (Vimpat®, as a novel tool for preferentially targeting CRMP2-mediated neurite outgrowth. Whereas (S-LCM was ineffective in targeting VGSCs, the presumptive pharmacological targets of (R-LCM, (S-LCM was more efficient than (R-LCM in subverting neurite outgrowth. Biomolecular interaction analyses revealed that (S-LCM bound to wildtype CRMP2 with low micromolar affinity, similar to (R-LCM. Through the use of this novel tool, the activity-dependent increase in neurite outgrowth observed following depolarization was characterized to be reliant on CRMP2 function. Knockdown of CRMP2 by siRNA in cortical neurons resulted in reduced CRMP2-dependent neurite outgrowth; incubation with (S-LCM phenocopied this effect. Other CRMP2-mediated processes were unaffected. (S-LCM subverted neurite outgrowth not by affecting the canonical CRMP2-tubulin association but rather by impairing the ability of CRMP2 to promote tubulin polymerization, events that are

  2. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    Energy Technology Data Exchange (ETDEWEB)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Makboul, Rania [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Pathology Department, Assiut University, Assiut (Egypt); Chadalawada, Gita; Chen, Ying [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Crawford, Susan E. [Department of Pathology, Saint Louis University School of Medicine, 1402 South Grand Blvd, Saint Louis, MO 63104 (United States); Savkovic, Suzana D., E-mail: ssavkovi@tulane.edu [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States)

    2016-01-15

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  3. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    International Nuclear Information System (INIS)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe; Makboul, Rania; Chadalawada, Gita; Chen, Ying; Crawford, Susan E.; Savkovic, Suzana D.

    2016-01-01

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  4. Activation of PPARγ mediates icaritin-induced cell cycle arrest and apoptosis in glioblastoma multiforme.

    Science.gov (United States)

    Liu, Yongji; Shi, Ling; Liu, Yuan; Li, Peng; Jiang, Guoping; Gao, Xiaoning; Zhang, Yongbin; Jiang, Chuanwu; Zhu, Weiping; Han, Hongxing; Ju, Fang

    2018-04-01

    Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro. Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays. Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPARγ played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPARγ. Our results suggest the PPARγ may mediate anti-neoplastic activities against GBM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Cerebral Blood Flow Responses to Aquatic Treadmill Exercise.

    Science.gov (United States)

    Parfitt, Rhodri; Hensman, Marianne Y; Lucas, Samuel J E

    2017-07-01

    Aquatic treadmills are used as a rehabilitation method for conditions such as spinal cord injury, osteoarthritis, and stroke, and can facilitate an earlier return to exercise training for athletes. However, their effect on cerebral blood flow (CBF) responses has not been examined. We tested the hypothesis that aquatic treadmill exercise would augment CBF and lower HR compared with land-based treadmill exercise. Eleven participants completed incremental exercise (crossover design) starting from walking pace (4 km·h, immersed to iliac crest [aquatic], 6 km·h [land]) and increasing 1 km·h every 2 min up to 10 km·h for aquatic (maximum belt speed) or 12 km·h for land. After this, participants completed two 2-min bouts of exercise immersed to midthigh and midchest at constant submaximal speed (aquatic), or were ramped to exhaustion (land; increased gradient 2° every min). Middle cerebral artery blood flow velocity (MCAv) and HR were measured throughout, and the initial 10 min of each protocol and responses at each immersion level were compared. Compared with land-based treadmill, MCAvmean increased more from baseline for aquatic exercise (21% vs 12%, P aquatic walking compared with land-based moderate intensity running (~10 cm·s, P = 0.56). Greater water immersion lowered HR (139 vs 178 bpm for midchest vs midthigh), whereas MCAvmean remained constant (P = 0.37). Findings illustrate the potential for aquatic treadmill exercise to enhance exercise-induced elevations in CBF and thus optimize shear stress-mediated adaptation of the cerebrovasculature.

  6. CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

    Science.gov (United States)

    Hakimé, Antoine; Peddi, Himaja; Hines-Peralta, Andrew U; Wilcox, Carol J; Kruskal, Jonathan; Lin, Shezhang; de Baere, Thierry; Raptopoulos, Vassilios D; Goldberg, S Nahum

    2007-06-01

    To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model. All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume. Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P=.01). Multisection CT perfusion techniques may provide an accurate and more reproducible

  7. Plant-mediated CH4 transport and C gas dynamics quantified in-situ in a Phalaris arundinacea-dominant wetland

    DEFF Research Database (Denmark)

    Jensen, Louise Askær; Elberling, Bo; Friborg, Thomas

    2011-01-01

    passive. Thus, diurnal variations are less important in contrast to wetland vascular plants facilitating convective gas flow. Despite of plant-dominant CH4 transport, net CH4 fluxes were low (–0.005–0.016 µmol m-2 s-1) and annually less than 1% of the annual C-CO2 assimilation. This is considered a result......±35% of ecosystem CH4 emissions were plant-mediated, but data show no evidence of significant diurnal variations related to convective gas flow regardless of season or plant growth stages. Therefore, despite a high percentage of arenchyma, P. arundinacea-mediated CH4 transport is interpreted to be predominantly...

  8. Dynamics of lava flow - Thickness growth characteristics of steady two-dimensional flow

    Science.gov (United States)

    Park, S.; Iversen, J. D.

    1984-01-01

    The thickness growth characteristics of flowing lava are investigated using a heat balance model and a two-dimensional model for flow of a Bingham plastic fluid down an inclined plane. It is found that yield strength plays a crucial role in the thickening of a lava flow of given flow rate. To illustrate this point, downstream thickness profiles and yield strength distributions were calculated for flows with mass flow rates of 10,000 and 100,000 kg/m-sec. Higher flow rates led to slow cooling rates which resulted in slow rate of increase of yield strength and thus greater flow lengths.

  9. What the Logs Can Tell You: Mediation to Implement Feedback in Training

    Science.gov (United States)

    Maluf, David; Wiederhold, Gio; Abou-Khalil, Ali; Norvig, Peter (Technical Monitor)

    2000-01-01

    The problem addressed by Mediation to Implement Feedback in Training (MIFT) is to customize the feedback from training exercizes by exploiting knowledge about the training scenario, training objectives, and specific student/teacher needs. We achieve this by inserting an intelligent mediation layer into the information flow from observations collected during training exercises to the display and user interface. Knowledge about training objectives, scenarios, and tasks is maintained in the mediating layer. A designer constraint is that domain experts must be able to extend mediators by adding domain-specific knowledge that supports additional aggregations, abstractions, and views of the results of training exercises. The MIFT mediation concept is intended to be integrated with existing military training exercise management tools and reduce the cost of developing and maintaining separate feedback and evaluation tools for every training simulator and every set of customer needs. The MIFT Architecture is designed as a set of independently reusable components which interact with each other through standardized formalisms such as the Knowledge Interchange Format (KIF) and Knowledge Query and Manipulation Language (KQML).

  10. Hydrodynamics of piston-driven laminar pulsating flow: Part 2. Fully developed flow

    International Nuclear Information System (INIS)

    Aygun, Cemalettin; Aydin, Orhan

    2014-01-01

    Highlights: • The piston-driven laminar pulsating flow in a pipe is studied. • Fully developed flow is examined analytically, numerically and experimentally. • An increase in F results an increase in the amplitude of the centerline velocity. • The characters of the radial velocity profiles critically depend on both the frequency and the phase angle. • The near/off-wall flow reversals are observed for F = 105, 226 and 402. - Abstract: Piston-driven pulsating flow is a specific type of pressure-driven pulsating flows. In this study, piston-driven laminar pulsating flow in a pipe is studied. This study mainly exists of two parts: developing flow and fully developed flow. In this part, hydrodynamically fully developed flow is examined analytically, numerically and experimentally. A constant value of the time-averaged Reynolds number is considered, Re = 1000. In the theoretical studies, both analytical and numerical, an inlet velocity profile representing the experimental case, i.e., the piston driven flow, is assumed. In the experiments, in the hydrodynamically fully developed region, radial velocity distribution and pressure drop are obtained using hot-wire anemometer and pressure transmitter, respectively. The effect pulsation frequency on the friction coefficient as well as velocity profiles are obtained. A good agreement is observed among analytical, numerical and experimental results

  11. Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions.

    Science.gov (United States)

    Zhang, Feng-Lin; Shen, Guo-Min; Liu, Xiao-Ling; Wang, Fang; Zhao, Ying-Ze; Zhang, Jun-Wu

    2012-08-01

    Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type-specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34(+) haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl(2) induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1-mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  12. Fibro-vascular coupling in the control of cochlear blood flow.

    Directory of Open Access Journals (Sweden)

    Min Dai

    Full Text Available Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained.We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca(2+ signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca(2+ sensor, fluo-4. Elevation of Ca(2+ in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca(2+ signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF. Cyclooxygenase-1 (COX-1 was required for capillary dilation.The findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity.

  13. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  14. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    ) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18......Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP...

  15. Sodium flow measurement in large pipelines of sodium cooled fast breeder reactors with bypass type flow meters

    International Nuclear Information System (INIS)

    Rajan, K.K.; Jayakumar, T.; Aggarwal, P.K.; Vinod, V.

    2016-01-01

    Highlights: • Bypass type permanent magnet flow meters are more suitable for sodium flow measurement. • A higher sodium velocity through the PMFM sensor will increase its sensitivity and resolution. • By modifying the geometry of bypass line, higher sodium velocity through sensor is achieved. • With optimized geometry the sensitivity of bypass flow meter system was increased by 70%. - Abstract: Liquid sodium flow through the pipelines of sodium cooled fast breeder reactor circuits are measured using electromagnetic flow meters. Bypass type flow meter with a permanent magnet flow meter as sensor in the bypass line is selected for the flow measurement in the 800 NB main secondary pipe line of 500 MWe Prototype Fast Breeder Reactor (PFBR), which is at the advanced stage of construction at Kalpakkam. For increasing the sensitivity of bypass flow meters in future SFRs, alternative bypass geometry was considered. The performance enhancement of the proposed geometry was evaluated by experimental and numerical methods using scaled down models. From the studies it is observed that the new configuration increases the sensitivity of bypass flow meter system by around 70%. Using experimentally validated numerical tools the volumetric flow ratio for the bypass configurations is established for the operating range of Reynolds numbers.

  16. Glutamine-enriched enteral diet increases splanchnic blood flow in the rat

    NARCIS (Netherlands)

    Houdijk, A. P.; van Leeuwen, P. A.; Boermeester, M. A.; van Lambalgen, T.; Teerlink, T.; FLINKERBUSCH, E. L.; Sauerwein, H. P.; Wesdorp, R. I.

    1994-01-01

    The hemodynamic consequences of glutamine (Gln)-enriched nutrition have not been investigated. This study investigates the effects of a Gln-enriched enteral diet on organ blood flows and systemic hemodynamics. Male Fischer 344 rats (n = 24) were randomized to a group that received a 12.5% (wt/wt)

  17. Increased Agrobacterium-mediated transformation and rooting efficiencies in canola (Brassica napus L.) from hypocotyl segment explants

    Science.gov (United States)

    Cardoza, V.; Stewart, C. N.

    2003-01-01

    An efficient protocol for the production of transgenic Brassica napus cv. Westar plants was developed by optimizing two important parameters: preconditioning time and co-cultivation time. Agrobacterium tumefaciens-mediated transformation was performed using hypocotyls as explant tissue. Two variants of a green fluorescent protein (GFP)-encoding gene--mGFP5-ER and eGFP--both under the constitutive expression of the cauliflower mosaic virus 35S promoter, were used for the experiments. Optimizing the preconditioning time to 72 h and co-cultivation time with Agrobacterium to 48 h provided the increase in the transformation efficiency from a baseline of 4% to 25%. With mGFP5-ER, the transformation rate was 17% and with eGFP it was 25%. Transgenic shoots were selected on 200 mg/l kanamycin. Rooting efficiency was 100% on half-strength Murashige and Skoog medium with 10 g/l sucrose and 0.5 mg/l indole butyric acid in the presence of kanamycin.

  18. Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles

    International Nuclear Information System (INIS)

    Uemura, N.; Knight, D.R.; Shen, Y.T.; Nejima, J.; Cohen, M.V.; Thomas, J.X. Jr.; Vatner, S.F.

    1989-01-01

    Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 ± 5.1%) than mongrels (42.5 ± 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO

  19. Debris flow-induced topographic changes: effects of recurrent debris flow initiation.

    Science.gov (United States)

    Chen, Chien-Yuan; Wang, Qun

    2017-08-12

    Chushui Creek in Shengmu Village, Nantou County, Taiwan, was analyzed for recurrent debris flow using numerical modeling and geographic information system (GIS) spatial analysis. The two-dimensional water flood and mudflow simulation program FLO-2D were used to simulate debris flow induced by rainfall during typhoon Herb in 1996 and Mindulle in 2004. Changes in topographic characteristics after the debris flows were simulated for the initiation of hydrological characteristics, magnitude, and affected area. Changes in topographic characteristics included those in elevation, slope, aspect, stream power index (SPI), topographic wetness index (TWI), and hypsometric curve integral (HI), all of which were analyzed using GIS spatial analysis. The results show that the SPI and peak discharge in the basin increased after a recurrence of debris flow. The TWI was higher in 2003 than in 2004 and indicated higher potential of landslide initiation when the slope of the basin was steeper. The HI revealed that the basin was in its mature stage and was shifting toward the old stage. Numerical simulation demonstrated that the parameters' mean depth, maximum depth, affected area, mean flow rate, maximum flow rate, and peak flow discharge were increased after recurrent debris flow, and peak discharge occurred quickly.

  20. Decreased arterial PO2, not O2 content, increases blood flow through intrapulmonary arteriovenous anastomoses at rest.

    Science.gov (United States)

    Duke, Joseph W; Davis, James T; Ryan, Benjamin J; Elliott, Jonathan E; Beasley, Kara M; Hawn, Jerold A; Byrnes, William C; Lovering, Andrew T

    2016-09-01

    The mechanism(s) that regulate hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) are currently unknown. Our previous work has demonstrated that the mechanism of hypoxia-induced QIPAVA is not simply increased cardiac output, pulmonary artery systolic pressure or sympathetic nervous system activity and, instead, it may be a result of hypoxaemia directly. To determine whether it is reduced arterial PO2 (PaO2) or O2 content (CaO2) that causes hypoxia-induced QIPAVA , individuals were instructed to breathe room air and three levels of hypoxic gas at rest before (control) and after CaO2 was reduced by 10% by lowering the haemoglobin concentration (isovolaemic haemodilution; Low [Hb]). QIPAVA , assessed by transthoracic saline contrast echocardiography, significantly increased as PaO2 decreased and, despite reduced CaO2 (via isovolaemic haemodilution), was similar at iso-PaO2. These data suggest that, with alveolar hypoxia, low PaO2 causes the hypoxia-induced increase in QIPAVA , although where and how this is detected remains unknown. Alveolar hypoxia causes increased blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) in healthy humans at rest. However, it is unknown whether the stimulus regulating hypoxia-induced QIPAVA is decreased arterial PO2 (PaO2) or O2 content (CaO2). CaO2 is known to regulate blood flow in the systemic circulation and it is suggested that IPAVA may be regulated similar to the systemic vasculature. Thus, we hypothesized that reduced CaO2 would be the stimulus for hypoxia-induced QIPAVA . Blood volume (BV) was measured using the optimized carbon monoxide rebreathing method in 10 individuals. Less than 5 days later, subjects breathed room air, as well as 18%, 14% and 12.5% O2 , for 30 min each, in a randomized order, before (CON) and after isovolaemic haemodilution (10% of BV withdrawn and replaced with an equal volume of 5% human serum albumin-saline mixture) to reduce [Hb] (Low [Hb]). PaO2

  1. Nephron blood flow dynamics measured by laser speckle contrast imaging

    DEFF Research Database (Denmark)

    von Holstein-Rathlou, Niels-Henrik; Sosnovtseva, Olga V; Pavlov, Alexey N

    2011-01-01

    Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular...... simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50-100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic...... pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons...

  2. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  3. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  4. Numerical simulation of nanofluid flow over diamond-shaped elements in tandem in laminar and turbulent flow

    Directory of Open Access Journals (Sweden)

    Hamed Safikhani

    2017-07-01

    Full Text Available In this paper, the Al2O3-water nanofluid flow in laminar and turbulent flows inside tubes fitted with diamond-shaped turbulators is numerically modeled. The nanofluid flow is modeled by employing a two-phase mixture method and applying the constant heat flux boundary condition at tube walls. In the results, the effects of different parameters such as the geometry of turbulators, volume fraction and diameter of nanoparticles, etc. on the flow field in the tubes have been investigated. The obtained results indicate that, with the reduction of tail length ratio (TR and increase of vertex angle of turbulators (θ, the heat transfer coefficient as well as the wall shear stress increase. Similarly, with the reduction of TR and increase of θ, the amount of secondary flows, vortices and the turbulent kinetic energy increase. Moreover, the increase in the volume fraction of nanoparticles and the reduction of nanoparticles diameter lead to the increase of the heat transfer coefficient and wall shear stress.

  5. Trajectories of late-life change in God-mediated control.

    Science.gov (United States)

    Hayward, R David; Krause, Neal

    2013-01-01

    To track within-individual change during late life in the sense of personal control and God-mediated control (the belief that one can work collaboratively with God to achieve one's goals and exercise control over life events) and to evaluate the hypothesis that this element of religion is related to declining personal control. A longitudinal survey representative of older White and Black adults in the United States tracked changes in personal and God-mediated control in four waves over the course of 7 years. Growth curve analysis found that the pattern of change differed by race. White adults had less sense of God-mediated control at younger ages, which increased among those who were highly religious but decreased among those who were less religious. Black adults had higher God-mediated control, which increased over time among those with low personal control. These results indicate that God-mediated control generally increases during older adulthood, but that its relationships with personal control and religious commitment are complex and differ between Black and White adults.

  6. Intracellular Signaling Mediators in the Circulatory and Ventilatory Systems

    CERN Document Server

    Thiriet, Marc

    2013-01-01

    The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors.  Activation of...

  7. Focal increase of cerebral blood flow during stereognostic testing in man

    DEFF Research Database (Denmark)

    Roland, E; Larsen, B

    1976-01-01

    An attempt was made to study the regional cerebral blood flow (rCBF) pattern during stereognostic discrimination in man. The rCBF was measured in 18 subjects who had no major neurological defects. The clearance from the hemisphere of xenon 133 injected (133Xe) into the carotid artery was measured...

  8. Mediator Undergoes a Compositional Change during Transcriptional Activation.

    Science.gov (United States)

    Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

    2016-11-03

    Mediator is a transcriptional co-activator recruited to enhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of the preinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter in vivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase module associates strongly with the enhancer, but not with the core promoter, and it dissociates from the enhancer upon depletion of the TFIIH kinase. Severing the kinase module from Mediator by removing the connecting subunit Med13 does not affect Mediator association at the core promoter but increases occupancy at enhancers. Thus, Mediator undergoes a compositional change in which the kinase module, recruited via Mediator to the enhancer, dissociates from Mediator to permit association with Pol II and the PIC. As such, Mediator acts as a dynamic bridge between the enhancer and core promoter. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Visual detection of West Nile virus using reverse transcription loop-mediated isothermal amplification combined with a vertical flow visualization strip

    Directory of Open Access Journals (Sweden)

    Zengguo eCao

    2016-04-01

    Full Text Available West Nile virus (WNV causes a severe zoonosis, which can lead to a large number of casualties and considerable economic losses. A rapid and accurate identification methodfor WNV for use in field laboratories is urgently needed. Here, a method utilizing reverse transcription loop-mediated isothermal amplification combined with a vertical flow visualization strip (RT-LAMP-VF was developed to detect the envelope (E gene of WNV. The RT-LAMP-VF assay could detect 102 copies/μl ofan WNV RNA standard using a 40 min amplification reaction followed by a 2 min incubationof the amplification product on the visualization strip, and no cross-reaction with other closely related members of theFlavivirus genus was observed. The assay was further evaluated using cells and mouse brain tissues infected with a recombinant rabies virus expressing the E protein of WNV.The assay produced sensitivities of 101.5TCID50/ml and 101.33 TCID50/ml for detection of the recombinant virus in the cells and brain tissues, respectively. Overall, the RT-LAMP-VF assay developed in this study is rapid, simple and effective, and it is therefore suitable for clinical application in the field.

  10. Increasing Responsive Parent–Child Interactions and Joint Engagement: Comparing the Influence of Parent-Mediated Intervention and Parent Psychoeducation

    Science.gov (United States)

    Gulsrud, Amanda; Kasari, Connie

    2016-01-01

    Enhancing immediate and contingent responding by caregivers to children’s signals is an important strategy to support social interactions between caregivers and their children with autism. Yet, there has been limited examination of parents’ responsive behaviour in association with children’s social behaviour post caregiver-mediated intervention. Eighty-five dyads were randomized to one of two 10-week caregiver-training interventions. Parent–child play interactions were coded for parental responsivity and children’s joint engagement. Significant gains in responsivity and time jointly engaged were found post JASPER parent-mediated intervention over a psychoeducation intervention. Further, combining higher levels of responsive behaviour with greater adoption of intervention strategies was associated with greater time jointly engaged. Findings encourage a focus on enhancing responsive behaviour in parent-mediated intervention models. PMID:26797940

  11. Marked Increase in Flow Velocities During Deep Expiration: A Duplex Doppler Sign of Celiac Artery Compression Syndrome

    International Nuclear Information System (INIS)

    Erden, Ayse; Yurdakul, Mehmet; Cumhur, Turhan

    1999-01-01

    Symptoms of chronic mesenteric ischemia develop when the celiac artery is constricted by the median arcuate ligament of the diaphragm. Lateral aortography is the primary modality for diagnosing ligamentous compression of the celiac artery. However, duplex Doppler sonography performed during deep expiration can cause a marked increase in flow velocities at the compressed region of the celiac artery and suggest the diagnosis of celiac arterial constriction due to the diaphragmatic ligament. RID='''' ID='''' Correspondence to: A. Erden, M.D., Hafta sokak. 23/6, Gaziosmanpasa, 06700 Ankara, Turkey

  12. Mediators of Yoga and Stretching for Chronic Low Back Pain

    Directory of Open Access Journals (Sweden)

    Karen J. Sherman

    2013-01-01

    Full Text Available Although yoga is an effective treatment for chronic low back pain, little is known about the mechanisms responsible for its benefits. In a trial comparing yoga to intensive stretching and self-care, we explored whether physical (hours of back exercise/week, cognitive (fear avoidance, body awareness, and self-efficacy, affective (psychological distress, perceived stress, positive states of mind, and sleep, and physiological factors (cortisol, DHEA mediated the effects of yoga or stretching on back-related dysfunction (Roland-Morris Disability Scale (RDQ. For yoga, 36% of the effect on 12-week RDQ was mediated by increased self-efficacy, 18% by sleep disturbance, 9% by hours of back exercise, and 61% by the best combination of all possible mediators (6 mediators. For stretching, 23% of the effect was mediated by increased self-efficacy, 14% by days of back exercise, and 50% by the best combination of all possible mediators (7 mediators. In open-ended questions, ≥20% of participants noted the following treatment benefits: learning new exercises (both groups, relaxation, increased awareness, and the benefits of breathing (yoga, benefits of regular practice (stretching. Although both self-efficacy and hours of back exercise were the strongest mediators for each intervention, compared to self-care, qualitative data suggest that they may exert their benefits through partially distinct mechanisms.

  13. Materialism and well-being among Chinese college students: the mediating role of basic psychological need satisfaction.

    Science.gov (United States)

    Chen, Yongjie; Yao, Meilin; Yan, Wenfan

    2014-10-01

    Based on self-determination theory, this study explored the potential mediating role of basic psychological need satisfaction in the relationship between materialism and well-being among Chinese college students. The results showed that basic psychological need satisfaction partially mediated the relationship between materialism and life satisfaction and fully mediated the relationships among materialism and emotional well-being, subjective vitality, and self-actualization. The findings indicated the importance of considering both subjective and psychological well-being and the interpretative power of basic psychological need satisfaction and Chinese culture in the flow from materialism to well-being. © The Author(s) 2013.

  14. Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction.

    Science.gov (United States)

    Liu, Yan; Li, Dan; Zhang, Yuhua; Sun, Ruifang; Xia, Min

    2014-04-15

    Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-β-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.

  15. Innovative model-based flow rate optimization for vanadium redox flow batteries

    Science.gov (United States)

    König, S.; Suriyah, M. R.; Leibfried, T.

    2016-11-01

    In this paper, an innovative approach is presented to optimize the flow rate of a 6-kW vanadium redox flow battery with realistic stack dimensions. Efficiency is derived using a multi-physics battery model and a newly proposed instantaneous efficiency determination technique. An optimization algorithm is applied to identify optimal flow rates for operation points defined by state-of-charge (SoC) and current. The proposed method is evaluated against the conventional approach of applying Faraday's first law of electrolysis, scaled to the so-called flow factor. To make a fair comparison, the flow factor is also optimized by simulating cycles with different charging/discharging currents. It is shown through the obtained results that the efficiency is increased by up to 1.2% points; in addition, discharge capacity is also increased by up to 1.0 kWh or 5.4%. Detailed loss analysis is carried out for the cycles with maximum and minimum charging/discharging currents. It is shown that the proposed method minimizes the sum of losses caused by concentration over-potential, pumping and diffusion. Furthermore, for the deployed Nafion 115 membrane, it is observed that diffusion losses increase with stack SoC. Therefore, to decrease stack SoC and lower diffusion losses, a higher flow rate during charging than during discharging is reasonable.

  16. Blood flow restriction training and the exercise pressor reflex: a call for concern.

    Science.gov (United States)

    Spranger, Marty D; Krishnan, Abhinav C; Levy, Phillip D; O'Leary, Donal S; Smith, Scott A

    2015-11-01

    Blood flow restriction (BFR) training (also known as Kaatsu training) is an increasingly common practice employed during resistance exercise by athletes attempting to enhance skeletal muscle mass and strength. During BFR training, blood flow to the exercising muscle is mechanically restricted by placing flexible pressurizing cuffs around the active limb proximal to the working muscle. This maneuver results in the accumulation of metabolites (e.g., protons and lactic acid) in the muscle interstitium that increase muscle force and promote muscle growth. Therefore, the premise of BFR training is to simulate and receive the benefits of high-intensity resistance exercise while merely performing low-intensity resistance exercise. This technique has also been purported to provide health benefits to the elderly, individuals recovering from joint injuries, and patients undergoing cardiac rehabilitation. Since the seminal work of Alam and Smirk in the 1930s, it has been well established that reductions in blood flow to exercising muscle engage the exercise pressor reflex (EPR), a reflex that significantly contributes to the autonomic cardiovascular response to exercise. However, the EPR and its likely contribution to the BFR-mediated cardiovascular response to exercise is glaringly missing from the scientific literature. Inasmuch as the EPR has been shown to generate exaggerated increases in sympathetic nerve activity in disease states such as hypertension (HTN), heart failure (HF), and peripheral artery disease (PAD), concerns are raised that BFR training can be used safely for the rehabilitation of patients with cardiovascular disease, as has been suggested. Abnormal BFR-induced and EPR-mediated cardiovascular complications generated during exercise could precipitate adverse cardiovascular or cerebrovascular events (e.g., cardiac arrhythmia, myocardial infarction, stroke and sudden cardiac death). Moreover, although altered EPR function in HTN, HF, and PAD underlies our

  17. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  18. Transition to magnetorotational turbulence in Taylor–Couette flow with imposed azimuthal magnetic field

    International Nuclear Information System (INIS)

    A Guseva; Avila, M; Willis, A P; Hollerbach, R

    2015-01-01

    The magnetorotational instability (MRI) is thought to be a powerful source of turbulence and momentum transport in astrophysical accretion discs, but obtaining observational evidence of its operation is challenging. Recently, laboratory experiments of Taylor–Couette flow with externally imposed axial and azimuthal magnetic fields have revealed the kinematic and dynamic properties of the MRI close to the instability onset. While good agreement was found with linear stability analyses, little is known about the transition to turbulence and transport properties of the MRI. We here report on a numerical investigation of the MRI with an imposed azimuthal magnetic field. We show that the laminar Taylor–Couette flow becomes unstable to a wave rotating in the azimuthal direction and standing in the axial direction via a supercritical Hopf bifurcation. Subsequently, the flow features a catastrophic transition to spatio-temporal defects which is mediated by a subcritical subharmonic Hopf bifurcation. Our results are in qualitative agreement with the PROMISE experiment and dramatically extend their realizable parameter range. We find that as the Reynolds number increases defects accumulate and grow into turbulence, yet the momentum transport scales weakly. (paper)

  19. The incremental value of brachial flow-mediated dilation measurements in risk stratification for incident cardiovascular events: a systematic review.

    Science.gov (United States)

    Peters, Sanne A E; den Ruijter, Hester M; Bots, Michiel L

    2012-06-01

    Abstract Adequate risk assessment for cardiovascular disease (CVD) is essential as a guide to initiate drug treatment. Current methods based on traditional risk factors could be improved considerably. Although brachial flow-mediated dilation (FMD) predicts subsequent cardiovascular events, its predictive value on top of traditional risk factors is unknown. We performed a systematic review to evaluate the incremental predictive value of FMD on top of traditional risk factors in asymptomatic individuals. Using PubMed and reference tracking, three studies were identified that reported on the incremental value of FMD using change in the area under the curve (AUC). Two large cohort studies found no improvement in AUC when FMD was added to traditional risk prediction models, whereas one small case-control study found an improvement. One study used the net reclassification improvement (NRI) to assess whether FMD measurement leads to correct risk stratification in risk categories. Although this study did not find an improvement in AUC, the NRI was statistically significant. Based on the reclassification results of this study, FMD measurement might be helpful in risk prediction. Evidence supporting the use of FMD measurement in clinical practice for risk stratification for CVD on top of traditional risk factors is limited, and future studies are needed.

  20. Increased Hydrologic Connectivity: Consequences of Reduced Water Storage Capacity in the Delmarva Peninsula (U.S.)

    Science.gov (United States)

    Mclaughlin, D. L.; Jones, C. N.; Evenson, G. R.; Golden, H. E.; Lane, C.; Alexander, L. C.; Lang, M.

    2017-12-01

    Combined geospatial and modeling approaches are required to fully enumerate wetland hydrologic connectivity and downstream effects. Here, we utilized both geospatial analysis and hydrologic modeling to explore drivers and consequences of modified surface water connectivity in the Delmarva Peninsula, with particular focus on increased connectivity via pervasive wetland ditching. Our geospatial analysis quantified both historical and contemporary wetland storage capacity across the region, and suggests that over 70% of historical storage capacity has been lost due to this ditching. Building upon this analysis, we applied a catchment-scale model to simulate implications of reduced storage capacity on catchment-scale hydrology. In short, increased connectivity (and concomitantly reduced wetland water storage capacity) decreases catchment inundation extent and spatial heterogeneity, shortens cumulative residence times, and increases downstream flow variation with evident effects on peak and baseflow dynamics. As such, alterations in connectivity have implications for hydrologically mediated functions in catchments (e.g., nutrient removal) and downstream systems (e.g., maintenance of flow for aquatic habitat). Our work elucidates such consequences in Delmarva Peninsula while also providing new tools for broad application to target wetland restoration and conservation. Views expressed are those of the authors and do not necessarily reflect policies of the US EPA or US FWS.

  1. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    Science.gov (United States)

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  2. Predictors of Parental Mediation Regarding Children's Smartphone Use.

    Science.gov (United States)

    Hwang, Yoori; Jeong, Se-Hoon

    2015-12-01

    Children's addiction to smartphones has become a serious issue, and parental mediation could help prevent children's problematic use of smartphones. This research examined the factors that predict and explain parents' intention to mediate children's behavior over smartphone use. Based on a survey of 460 parents of elementary school students, we found that parental mediation was predicted by (a) parent's own addiction to smartphones, (b) perceived severity of smartphone addiction, and (c) personality traits such as neuroticism, openness, and agreeableness. To the best of our knowledge, this study is the first to examine the predictors of parental mediation regarding children's smartphone addiction, and the findings suggest some strategies to increase parental mediation.

  3. TGF-β1-mediated differentiation of fibroblasts is associated with increased mitochondrial content and cellular respiration.

    Directory of Open Access Journals (Sweden)

    Ulugbek Negmadjanov

    Full Text Available Cytokine-dependent activation of fibroblasts to myofibroblasts, a key event in fibrosis, is accompanied by phenotypic changes with increased secretory and contractile properties dependent on increased energy utilization, yet changes in the energetic profile of these cells are not fully described. We hypothesize that the TGF-β1-mediated transformation of myofibroblasts is associated with an increase in mitochondrial content and function when compared to naive fibroblasts.Cultured NIH/3T3 mouse fibroblasts treated with TGF-β1, a profibrotic cytokine, or vehicle were assessed for transformation to myofibroblasts (appearance of α-smooth muscle actin [α-SMA] stress fibers and associated changes in mitochondrial content and functions using laser confocal microscopy, Seahorse respirometry, multi-well plate reader and biochemical protocols. Expression of mitochondrial-specific proteins was determined using western blotting, and the mitochondrial DNA quantified using Mitochondrial DNA isolation kit.Treatment with TGF-β1 (5 ng/mL induced transformation of naive fibroblasts into myofibroblasts with a threefold increase in the expression of α-SMA (6.85 ± 0.27 RU compared to cells not treated with TGF-β1 (2.52 ± 0.11 RU. TGF-β1 exposure increased the number of mitochondria in the cells, as monitored by membrane potential sensitive dye tetramethylrhodamine, and expression of mitochondria-specific proteins; voltage-dependent anion channels (0.54 ± 0.05 vs. 0.23 ± 0.05 RU and adenine nucleotide transporter (0.61 ± 0.11 vs. 0.22 ± 0.05 RU, as well as mitochondrial DNA content (530 ± 12 μg DNA/106 cells vs. 307 ± 9 μg DNA/106 cells in control. TGF-β1 treatment was associated with an increase in mitochondrial function with a twofold increase in baseline oxygen consumption rate (2.25 ± 0.03 vs. 1.13 ± 0.1 nmol O2/min/106 cells and FCCP-induced mitochondrial respiration (2.87 ± 0.03 vs. 1.46 ± 0.15 nmol O2/min/106 cells.TGF-β1 induced

  4. Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium.

    Directory of Open Access Journals (Sweden)

    Boa Kim

    Full Text Available Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2 for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm. Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta and muscle feed (femoral artery arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.

  5. Regular aerobic exercise reduces endothelin-1-mediated vasoconstrictor tone in overweight and obese adults.

    Science.gov (United States)

    Dow, Caitlin A; Stauffer, Brian L; Brunjes, Danielle L; Greiner, Jared J; DeSouza, Christopher A

    2017-09-01

    What is the central question of this study? Does aerobic exercise training reduce endothelin-1 (ET-1)-mediated vasoconstrictor tone in overweight/obese adults? And, if so, does lower ET-1 vasoconstriction underlie the exercise-related enhancement in endothelium-dependent vasodilatation in overweight/obese adults? What is the main finding and its importance? Regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight/obese adults, independent of weight loss. Decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. Although the effects of habitual aerobic exercise on endothelium-dependent vasodilatation in overweight/obese adults have been studied, little is known regarding ET-1-mediated vasoconstriction. Accordingly, the aims of the present study were to determine the following: (i) whether regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so, (ii) whether the reduction in ET-1-mediated vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilatation in this population. Forearm blood flow (FBF) in response to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol min -1 for 60 min), acetylcholine [4.0, 8.0 and 16.0 μg (100 ml tissue) -1  min -1 ] in the absence and presence of ET A receptor blockade and sodium nitroprusside [1.0, 2.0 and 4.0 μg (100 ml tissue) -1  min -1 ] were determined before and after a 3 month aerobic exercise training intervention in 25 (16 men and nine women) overweight/obese (body mass index 30.1 ± 0.5 kg m -2 ) adults. The vasodilator response to BQ-123 was

  6. Radical-Mediated Enzymatic Polymerizations

    Science.gov (United States)

    Zavada, Scott R.; Battsengel, Tsatsral; Scott, Timothy F.

    2016-01-01

    Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes―catalytic proteins―owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction-oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol–ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID:26848652

  7. Numerical simulation of internal flow in mixed-flow waterjet propulsion

    International Nuclear Information System (INIS)

    Wu, T T; Pan, Z Y; Zhang, D Q; Jia, Y Y

    2012-01-01

    In order to reveal the internal flow characteristic of a mixed-flow waterjet propulsion, a mixed-flow waterjet propulsion under different conditions was simulated based on multi-reference frame(MRF), the standard k − ε turbulent model and SIMPLEC algorithm. The relationship between pump performance instability and internal flow was obtained. The numerical results showed that characteristic instability occurred at 0.65-0.67Q BEP , the reason is that the backflow on the vaned diffuser hub-side blocks the downstream flow from the impeller. Therefore, the flow separates on the pressure surface of the impeller outlet and a strong vortex is generated, then the characteristic instability appeared due to the instability of internal flow. Backflow was found in diffuser passage at 0.65 Q BEP and 0.85 Q BEP , as flow rate decreases, the backflow region and velocity increases. Pressure fluctuation at diffuser inlet and diffuser passages was severe at at 0.65 Q BEP . According to the numerical simulation, the mixed-flow waterjet propulsion has characteristic instability at partial flow rate condition.

  8. Robust Mediation Analysis Based on Median Regression

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2014-01-01

    Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925

  9. Mediation analysis with multiple versions of the mediator.

    Science.gov (United States)

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  10. Standardized intermittent static exercise increases peritendinous blood flow in human leg

    DEFF Research Database (Denmark)

    Langberg, Henning; Bülow, J; Kjaer, M

    1999-01-01

    . The radioactive isotope xenon-133 was injected just ventrally to the Achilles tendon 5 cm proximal to the tendon's insertion on the calcaneous. The disappearance of 133Xe was used to determine blood flow during intermittent static exercise of the calf muscle (1.5 s exercise/1.5 s rest) for 30 min at a workload...

  11. Enzyme mediated synthesis of polypyrrole in the presence of chondroitin sulfate and redox mediators of natural origin

    International Nuclear Information System (INIS)

    Grijalva-Bustamante, G.A.; Evans-Villegas, A.G.; Castillo-Castro, T. del; Castillo-Ortega, M.M.; Cruz-Silva, R.; Huerta, F.; Morallón, E.

    2016-01-01

    Polypyrrole (PPy) was synthesized by enzyme mediated oxidation of pyrrole using naturally occurring compounds as redox mediators. The catalytic mechanism is an enzymatic cascade reaction in which hydrogen peroxide is the oxidizer and soybean peroxidase, in the presence of acetosyringone, syringaldehyde or vanillin, acts as a natural catalysts. The effect of the initial reaction composition on the polymerization yield and electrical conductivity of PPy was analyzed. Morphology of the PPy particles was studied by scanning electron microscopy and transmission electron microscopy whereas the chemical structure was studied by X-ray photoelectron and Fourier transformed infrared spectroscopic techniques. The redox mediators increased the polymerization yield without a significant modification of the electronic structure of PPy. The highest conductivity of PPy was reached when chondroitin sulfate was used simultaneously as dopant and template during pyrrole polymerization. Electroactive properties of PPy obtained from natural precursors were successfully used in the amperometric quantification of uric acid concentrations. PPy increases the amperometric sensitivity of carbon nanotube screen-printed electrodes toward uric acid detection. - Highlights: • A new method of pyrrole polymerization using naturally occurring redox mediators and doping agents was studied. • The catalytic efficiency of different redox mediators toward pyrrole oxidation was evaluated. • Two different naturally occurring polymers were studied as bifunctional steric stabilizer/doping agents. • Polypyrrole improves the amperometric response of carbon nanotube screen printed electrodes toward uric acid sensing.

  12. Enzyme mediated synthesis of polypyrrole in the presence of chondroitin sulfate and redox mediators of natural origin

    Energy Technology Data Exchange (ETDEWEB)

    Grijalva-Bustamante, G.A. [Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Evans-Villegas, A.G. [Departamento de Ciencias Químico Biológicas, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Castillo-Castro, T. del, E-mail: terecat@polimeros.uson.mx [Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Castillo-Ortega, M.M. [Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Cruz-Silva, R. [Research Center for Exotic Nanocarbons, Shinshu University, 4-17-1 Wakasato, 380-8553, Nagano (Japan); Huerta, F. [Departamento Ingeniería Textil y Papelera, Universitat Politecnica de Valencia, Plaza Ferrandiz y Carbonell, 1, E-03801 Alcoy (Spain); Morallón, E. [Departamento Química Física e Instituto Universitario de Materiales, Universidad de Alicante, Ap. 99, E-03080 Alicante (Spain)

    2016-06-01

    Polypyrrole (PPy) was synthesized by enzyme mediated oxidation of pyrrole using naturally occurring compounds as redox mediators. The catalytic mechanism is an enzymatic cascade reaction in which hydrogen peroxide is the oxidizer and soybean peroxidase, in the presence of acetosyringone, syringaldehyde or vanillin, acts as a natural catalysts. The effect of the initial reaction composition on the polymerization yield and electrical conductivity of PPy was analyzed. Morphology of the PPy particles was studied by scanning electron microscopy and transmission electron microscopy whereas the chemical structure was studied by X-ray photoelectron and Fourier transformed infrared spectroscopic techniques. The redox mediators increased the polymerization yield without a significant modification of the electronic structure of PPy. The highest conductivity of PPy was reached when chondroitin sulfate was used simultaneously as dopant and template during pyrrole polymerization. Electroactive properties of PPy obtained from natural precursors were successfully used in the amperometric quantification of uric acid concentrations. PPy increases the amperometric sensitivity of carbon nanotube screen-printed electrodes toward uric acid detection. - Highlights: • A new method of pyrrole polymerization using naturally occurring redox mediators and doping agents was studied. • The catalytic efficiency of different redox mediators toward pyrrole oxidation was evaluated. • Two different naturally occurring polymers were studied as bifunctional steric stabilizer/doping agents. • Polypyrrole improves the amperometric response of carbon nanotube screen printed electrodes toward uric acid sensing.

  13. Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

    Science.gov (United States)

    Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J; Valenzuela, C Fernando; Savage, Daniel D

    2018-02-01

    We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H 3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H 3 receptor number and function. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. Radiohistochemical studies in adult offspring revealed that specific [ 3 H]-A349821 binding to histamine H 3 receptors was not different in PAE rats compared to controls. However, H 3 receptor-mediated G i /G o protein-effector coupling, as measured by methimepip-stimulated [ 35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H 3 receptor population without significantly altering the affinities of H 3 receptor subpopulations. In agreement with the [ 35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. These results suggest that a PAE-induced elevation in H 3 receptor-mediated inhibition of glutamate release from

  14. Two-phase flow regimes for counter-current air-water flows in narrow rectangular channels

    International Nuclear Information System (INIS)

    Kim, Byong Joo; Sohn, Byung Hu; Jeong, Si Young

    2001-01-01

    A study of counter-current two-phase flow in narrow rectangular channels has been performed. Two-phase flow regimes were experimentally investigated in a 760 mm long and 100 mm wide test section with 2.0 and 5.0 mm gap widths. The resulting flow regime maps were compared with the existing transition criteria. The experimental data and the transition criteria of the models showed relatively good agreement. However, the discrepancies between the experimental data and the model predictions of the flow regime transition became pronounced as the gap width increased. As the gap width increased the transition gas superficial velocities increased. The critical void fraction for the bubbly-to-slug transition was observed to be about 0.25. The two-phase distribution parameter for the slug flow was larger for the narrower channel. The uncertainties in the distribution parameter could lead to a disagreement in slug-to-churn transition between the experimental findings and the transition criteria. For the transition from churn to annular flow the effect of liquid superficial velocity was found to be insignificant

  15. Understanding of the Interaction between Clearance Leakage Flow and Main Passage Flow in a VGT Turbine

    Directory of Open Access Journals (Sweden)

    Ben Zhao

    2015-02-01

    Full Text Available The clearance flow between the nozzle and endwall in a variable geometry turbine (VGT has been numerically investigated to understand the clearance effect on the VGT performance and internal flow. It was found that the flow rate through turbine increases but the turbine efficiency decreases with height of clearance. Detailed flow field analyses indicated that most of the efficiency loss resulting from the leakage flow occurs at the upstream of the rotor area, that is, in the nozzle endwall clearance and between the nozzle vanes. There are two main mechanisms associated with this efficiency loss. One is due to the formation of the local vortex flow structure between the clearance flow and the main flow. The other is due to the impact of the clearance flow on the main flow after the nozzle throat. This impact reduces the span of shockwave with increased shockwave magnitude by changing the trajectory of the main flow.

  16. CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Wei Hua

    Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

  17. Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

    Science.gov (United States)

    Rouine, J; Kelly, M E; Jennings-Murphy, C; Duffy, P; Gorman, I; Gormley, S; Kerskens, C M; Harkin, Andrew

    2015-05-01

    Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI. The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats. Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI. Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion. Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

  18. Diesel exhaust particles increase IL-1β-induced human β-defensin expression via NF-κB-mediated pathway in human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Lee Chun

    2006-05-01

    Full Text Available Abstract Background Human β-defensin (hBD-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8 expression to DEP exposure in interleukin-1 beta (IL-1β-stimulated A549 cells. Results IL-1β markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-κB activation in IL-1β-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-κB and degradation of IκB-α. The experiment using two NF-κB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-κB-mediated pathway. Conclusion These results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1β-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-κB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.

  19. The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

    DEFF Research Database (Denmark)

    Stenbøg, Elisabeth Vidstid; Steinbruchel, Daniel Andreas; Thomsen, Anne Bloch

    2001-01-01

    Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal....... By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure...... in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations....

  20. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  1. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  2. Three-dimensional numerical study of flow and heat transfer from a cube placed in a uniform flow

    International Nuclear Information System (INIS)

    Saha, A.K.

    2006-01-01

    The fluid flow and heat transfer from a stationary cube placed in a uniform flow is studied numerically. The three-dimensional unsteady Navier Stokes and energy equations are solved using higher order temporal and spatial discretizations. Computations are carried out for a Reynolds number range of 50-400. At Re = 218, the symmetry seen at Re = 216 breaks down in one of the orthogonal planes while remains symmetric on the other thus showing a planar symmetry. The flow experiences a Hopf bifurcation at a Reynolds number between 265 and 270 and becomes unsteady. The thermal field also shows all the transitions same as those of flow transitions. The drag coefficient decreases while the heat transfer shows an increasing trend with Reynolds number. The transition from a steady to an unsteady flow does not show any significant increase in the heat transfer. Both the flow and thermal fields show multiple frequencies at high Reynolds number and the number of frequencies increases with the increase in Reynolds number. The instantaneous flow and temperature field are seen to deviate from planar symmetry at Re = 400

  3. Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension.

    Science.gov (United States)

    Ritt, Martin; Harazny, Joanna M; Ott, Christian; Raff, Ulrike; Bauernschubert, Philipp; Lehmann, Marina; Michelson, Georg; Schmieder, Roland E

    2012-09-01

    We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=-0.216; P=0.023) but not diastolic blood pressure (β=-0.117; P=0.243) or mean arterial pressure (β=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0±51 versus 22.6±56 AU; P=0.731) or percent changes (7.12±16 versus 8.29±18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure.

  4. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  5. Increased SRP reactor power

    International Nuclear Information System (INIS)

    MacAfee, I.M.

    1983-01-01

    Major changes in the current reactor hydraulic systems could be made to achieve a total of about 1500 MW increase of reactor power for P, K, and C reactors. The changes would be to install new, larger heat exchangers in the reactor buildings to increase heat transfer area about 24%, to increase H 2 O flow about 30% per reactor, to increase D 2 O flow 15 to 18% per reactor, and increase reactor blanket gas pressure from 5 psig to 10 psig. The increased reactor power is possible because of reduced inlet temperature of reactor coolant, increased heat removal capacity, and increased operating pressure (larger margin from boiling). The 23% reactor power increase, after adjustment for increased off-line time for reactor reloading, will provide a 15% increase of production from P, K, and C reactors. Restart of L Reactor would increase SRP production 33%

  6. Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short-term hypotensive effect.

    Science.gov (United States)

    Bądzyńska, B; Sadowski, J

    2012-08-01

    Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  7. Role of blood flow and blood flow modifiers in clinical hyperthermia therapy

    International Nuclear Information System (INIS)

    Olch, A.J.

    1986-01-01

    A quantitative assessment of the effect of localized magnetic-loop hyperthermia on blood flow was performed on 12 patients (19 tumor studies) using the Xenon-133 clearance method. After it was discovered that blood flow in most of the tumors increased in response to needle injection, a physiologically based, one compartment model was developed that included both a hyperemic (transient) and a steady state component. In the tumors of six patients, increases in blood flow induced by heat were also observed. The same model was used to describe the measured clearance data for both types of hyperemic response. The ability of tumor vessels to respond dynamically to stress and the degree of response may be predictive of tumor heating efficiency and subsequent therapeutic response. Many tumors treated by hyperthermia, therefore, do not reach therapeutic temperatures (42 0 C). One explanation for this may be that some tumors react to thermal stress in a manner similar to normal tissues; i.e., they increase blood flow during hyperthermia in order to dissipate heat. Higher temperatures might be achieved in these heat-resistant tumors by administering vasoconstrictive agents in an effort to reduce blood flow. In the second part of this research study, the extent to which pharmacologic inhibition of local blood flow might allow higher temperatures to develop in normal muscles exposed to localized radiofrequency hyperthermia was determined. It was found that the local muscle temperature rise could be increased by at least 90% in dogs and rabbits with the use of a local vasoconstrictive drug

  8. Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

    Science.gov (United States)

    Khan, Meraj A.; Philip, Lijy M.; Cheung, Guillaume; Vadakepeedika, Shawn; Grasemann, Hartmut; Sweezey, Neil; Palaniyar, Nades

    2018-01-01

    Neutrophils migrating from the blood (pH 7.35–7.45) into the surrounding tissues encounter changes in extracellular pH (pHe) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units) increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements). Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging) during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs). In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots) and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative)-, and Staphylococcus aureus (Gram-positive)-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM) increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

  9. Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

    Directory of Open Access Journals (Sweden)

    Meraj A. Khan

    2018-02-01

    Full Text Available Neutrophils migrating from the blood (pH 7.35–7.45 into the surrounding tissues encounter changes in extracellular pH (pHe conditions. Upon activation of NADPH oxidase 2 (Nox, neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi. Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET formation (NETosis is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements. Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs. In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative-, and Staphylococcus aureus (Gram-positive-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

  10. Effects of Experimental High Flow Releases and Increased Fluctuations in Flow from Glen Canyon Dam on Abundance, Growth, and Survival Rates of Early Life Stages of Rainbow Trout in the Lee's Ferry Reach of the Colorado River

    Science.gov (United States)

    Korman, Josh

    2010-05-01

    The abundance of adult fish populations is controlled by the growth and survival rates of early life stages. Evaluating the effects of flow regimes on early life stages is therefore critical to determine how these regimes affect the abundance of adult populations. Experimental high flow releases from Glen Canyon Dam, primarily intended to conserve fine sediment and improve habitat conditions for native fish in the Colorado River in Grand Canyon, AZ, have been conducted in 1996, 2004, and 2008. These flows potentially affect the Lee's Ferry reach rainbow trout population, located immediately downstream of the dam, which supports a highly valued fishery and likely influences the abundance of rainbow trout in Grand Canyon. Due to concerns about negative effects of high trout abundance on endangered native fish, hourly variation in flow from Glen Canyon Dam was experimentally increased between 2003 and 2005 to reduce trout abundance. This study reports on the effects of experimental high flow releases and fluctuating flows on early life stages of rainbow trout in the Lee's Ferry reach based on monthly sampling of redds (egg nests) and the abundance and growth of age-0 trout between 2003 and 2009. Data on spawn timing, spawning elevations, and intergravel temperatures were integrated in a model to estimate the magnitude and seasonal trend in incubation mortality resulting from redd dewatering due to fluctuations in flow. Experimental fluctuations from January through March promoted spawning at higher elevations where the duration of dewatering was longer and intergravel temperatures exceeded lethal thresholds. Flow-dependent incubation mortality rates were 24% (2003) and 50% (2004) in years with higher flow fluctuations, compared to 5-11% under normal operations (2006-2009). Spatial and temporal predictions of mortality were consistent with direct observations of egg mortality determined from the excavation of 125 redds. The amount of variation in backcalculated hatch

  11. Autogenic dynamics of debris-flow fans

    Science.gov (United States)

    van den Berg, Wilco; de Haas, Tjalling; Braat, Lisanne; Kleinhans, Maarten

    2015-04-01

    Alluvial fans develop their semi-conical shape by cyclic avulsion of their geomorphologically active sector from a fixed fan apex. These cyclic avulsions have been attributed to both allogenic and autogenic forcings and processes. Autogenic dynamics have been extensively studied on fluvial fans through physical scale experiments, and are governed by cyclic alternations of aggradation by unconfined sheet flow, fanhead incision leading to channelized flow, channel backfilling and avulsion. On debris-flow fans, however, autogenic dynamics have not yet been directly observed. We experimentally created debris-flow fans under constant extrinsic forcings, and show that autogenic dynamics are a fundamental intrinsic process on debris-flow fans. We found that autogenic cycles on debris-flow fans are driven by sequences of backfilling, avulsion and channelization, similar to the cycles on fluvial fans. However, the processes that govern these sequences are unique for debris-flow fans, and differ fundamentally from the processes that govern autogenic dynamics on fluvial fans. We experimentally observed that backfilling commenced after the debris flows reached their maximum possible extent. The next debris flows then progressively became shorter, driven by feedbacks on fan morphology and flow-dynamics. The progressively decreasing debris-flow length caused in-channel sedimentation, which led to increasing channel overflow and wider debris flows. This reduced the impulse of the liquefied flow body to the flow front, which then further reduced flow velocity and runout length, and induced further in-channel sedimentation. This commenced a positive feedback wherein debris flows became increasingly short and wide, until the channel was completely filled and the apex cross-profile was plano-convex. At this point, there was no preferential transport direction by channelization, and the debris flows progressively avulsed towards the steepest, preferential, flow path. Simultaneously

  12. Light mediators in dark matter direct detections

    International Nuclear Information System (INIS)

    Li, Tai; Miao, Sen; Zhou, Yu-Feng

    2015-01-01

    In an extended effective operator framework, we investigate in detail the effects of light mediators on the event spectra of dark matter (DM)-nucleus scatterings. The presence of light mediators changes the interpretation of the current experimental data, especially the determination of DM particle mass. We show by analytic and numerical illustrations that in general for all the operators relevant to spin-independent scatterings, the DM particle mass allowed by a given set of experimental data increases significantly when the mediator particle becomes lighter. For instance, in the case of CDMS-II-Si experiment, the allowed DM particle mass can reach ∼50 (100) GeV at 68% (90%) confidence level, which is much larger than ∼10 GeV in the case with contact interactions. The increase of DM particle mass saturates when the mediator mass is below O(10) MeV. The upper limits from other experiments such as SuperCDMS, CDMSlite, CDEX, XENON10/100, LUX, PandaX etc. all tend to be weaker toward high DM mass regions. In a combined analysis, we show that the presence of light mediators can partially relax the tension in the current results of CDMS-II-Si, SuperCDMS and LUX

  13. What carries a mediation process? Configural analysis of mediation.

    Science.gov (United States)

    von Eye, Alexander; Mun, Eun Young; Mair, Patrick

    2009-09-01

    Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

  14. Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala.

    Science.gov (United States)

    Krishnan, Balaji; Scott, Michael T; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia

    2016-02-01

    Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. Published by Elsevier Inc.

  15. Experimental study on flow pattern transitions for inclined two-phase flow

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Nam Yee; Lee, Jae Young [Handong Univ., Pohang (Korea, Republic of); Kim, Man Woong [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2007-07-01

    In this paper, experimental data on flow pattern transition of inclination angles from 0-90 are presented. A test section is constructed 2 mm long and I.D 1inch using transparent material. The test section is supported by aluminum frame that can be placed with any arbitrary inclined angles. The air-water two-phase flow is observed at room temperature and atmospheric condition using both high speed camera and void impedance meter. The signal is sampled with sampling rate 1kHz and is analyzed under fully-developed condition. Based on experimental data, flow pattern maps are made for various inclination angles. As increasing the inclination angels from 0 to 90, the flow pattern transitions on the plane jg-jf are changed, such as stratified flow to plug flow or slug flow or plug flow to bubbly flow. The transition lines between pattern regimes are moved or sometimes disappeared due to its inclined angle.

  16. A development of multiphase flow facility

    International Nuclear Information System (INIS)

    Ismail Mustapha; Jaafar Abdullah

    2004-01-01

    Multiphase liquid flow facility shall be enabling to transport of oil/gas/water in pipelines. In horizontal pipelines, the different flow patterns that could be observed. The flow pattern will depend mainly on the gas and liquid velocities, and gas liquid ratio. For very high liquid velocities and low gas liquid ratios, the dispersed bubble flow is observed. For low flow rates of liquid and gas, a smooth or wavy stratified flow is expected. For intermediate liquid velocities, rolling waves of liquids are formed. The rolling waves increase to the point of forming a plug flow and a slug flow. For very high gas velocities, the annular flow is observed Also include a tillable test section allowing for testing at any angle between 0 0 degree from horizontal, lowering the measurement uncertainties and increased capabilities with respect to flow rates and gas fractions. (Author)

  17. A computational description of simple mediation analysis

    Directory of Open Access Journals (Sweden)

    Caron, Pier-Olivier

    2018-04-01

    Full Text Available Simple mediation analysis is an increasingly popular statistical analysis in psychology and in other social sciences. However, there is very few detailed account of the computations within the model. Articles are more often focusing on explaining mediation analysis conceptually rather than mathematically. Thus, the purpose of the current paper is to introduce the computational modelling within simple mediation analysis accompanied with examples with R. Firstly, mediation analysis will be described. Then, the method to simulate data in R (with standardized coefficients will be presented. Finally, the bootstrap method, the Sobel test and the Baron and Kenny test all used to evaluate mediation (i.e., indirect effect will be developed. The R code to implement the computation presented is offered as well as a script to carry a power analysis and a complete example.

  18. Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway.

    Science.gov (United States)

    Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

    2016-02-16

    Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function.

  19. GNMT Expression Increases Hepatic Folate Contents and Folate-Dependent Methionine Synthase-Mediated Homocysteine Remethylation

    OpenAIRE

    Wang, Yi-Cheng; Chen, Yi-Ming; Lin, Yan-Jun; Liu, Shih-Ping; Chiang, En-Pei Isabel

    2011-01-01

    Glycine N-methyltransferase (GNMT) is a major hepatic enzyme that converts S-adenosylmethionine to S-adenosylhomocysteine while generating sarcosine from glycine, hence it can regulate mediating methyl group availability in mammalian cells. GNMT is also a major hepatic folate binding protein that binds to, and, subsequently, may be inhibited by 5-methyltetrafolate. GNMT is commonly diminished in human hepatoma; yet its role in cellular folate metabolism, in tumorigenesis and antifolate therap...

  20. CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Nicolas Espagnolle

    2017-04-01

    Full Text Available Summary: Mesenchymal stromal cells (MSCs sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy. : Mesenchymal stromal cells (MSCs are promising for cell-based therapy in inflammatory disorders by switching off the immune response. Varin and colleagues demonstrate that MSCs and inflammatory macrophages communicate via an unconventional but functional interaction that strongly increases the immunosuppressive capacities of MSCs. This new communication between the innate immune system and MSCs opens new perspectives for MSC-based cell therapy. Keywords: macrophages, bone marrow mesenchymal stromal cells, functional interaction, CD54, immunosuppression, indoleamine 2,3-dioxygenase, cell therapy

  1. Groundwater dynamics mediate low-flow response to global warming in snow-dominated alpine regions

    Science.gov (United States)

    Christina Tague; Gordon E. Grant

    2009-01-01

    In mountain environments, spatial and temporal patterns of snow accumulation and melt are dominant controls on hydrologic responses to climate change. In this paper, we develop a simple conceptual model that links the timing of peak snowmelt with geologically mediated differences in rate of streamflow recession. This model demonstrates that within the western United...

  2. The new numerology of immunity mediated by virus-specific CD8(+) T cells.

    Science.gov (United States)

    Doherty, P C

    1998-08-01

    Our understanding of virus-specific CD8(+) T cell responses is currently being revolutionized by peptide-based assay systems that allow flow cytometric analysis of effector and memory cytotoxic T lymphocyte populations. These techniques are, for the first time, putting the analysis of T-cell-mediated immunity on a quantitative basis.

  3. Intercontinental gene flow among western arctic populations of Lesser Snow Geese

    Science.gov (United States)

    Shorey, Rainy I.; Scribner, Kim T.; Kanefsky, Jeannette; Samuel, Michael D.; Libants, Scot V.

    2011-01-01

    Quantifying the spatial genetic structure of highly vagile species of birds is important in predicting their degree of population demographic and genetic independence during changing environmental conditions, and in assessing their abundance and distribution. In the western Arctic, Lesser Snow G