Biokinetics of /sup 237/Np in mussels and shrimp

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

Guary, J.C.; Fowler, S.W.

1977-01-01

Neptunium-237 kinetics were studied in marine shrimp and mussels using a thick source alpha counting technique. Bioaccumulation of /sup 237/Np from water was relatively slow in both species, reaching whole body concentration factors of only 15 to 20 after three months. Surface adsorption was implicated in the initial uptake. Both uptake and loss of the radioisotope were not significantly affected by temperature; this may be a reflection of the physical nature of the uptake. By virtue of the large amounts of accumulated /sup 237/Np associated with the exoskeleton of shrimp, molting will play an important role in the biogeochemical cyclingmore » of this transuranic in the marine environment. Rapid growth of organisms like mussels acts to reduce the /sup 237/Np concentration in tissues during a period of decontamination.« less

Plant uptake of pentachlorophenol from sludge-amended soils

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

Bellin, C.A.; O'Connor, G.A.

A greenhouse study was conducted to determine the effects of sludge on plant uptake of {sup 14}C-pentachlorophenol (PCP). Plants included tall fescue (Festuca arundinacea Schreb.), lettuce (Latuca sativa L.), carrot (Daucus carota L.), and chile pepper (Capsicum annum L.). Minimal intact PCP was detected in the fescue and lettuce by gas chromatography/mass spectrometry (GC/MS) analysis. No intact PCP was detected in the carrot tissue extracts. Chile pepper was not analyzed for intact PCP because methylene chloride extracts contained minimal {sup 14}C. The GC/MS analysis of soil extracts at harvest suggests a half-life of PCP of about 10 d independent ofmore » sludge rate or PCP loading rate. Rapid degradation of PCP in the soil apparently limited PCP availability to the plant. Bioconcentration factors (dry plant wt./initial soil PCP concentration) based on intact PCP were <0.01 for all crops, suggesting little PCP uptake. Thus, food-chain crop PCP uptake in these alkaline soils should not limit land application of sludge.« less

Plant uptake of pentachlorophenol from sludge-amended soils

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

Bellin, C.A.; O'Connor, G.A.

A greenhouse study was conducted to determine the effects of sludge on plant uptake of {sup 14}C-pentachlorophenol (PCP). Plants included tall fescue (Festuca arundinacea Schreb.), lettuce (Latuca sativa L.), carrot (Daucus carota L.), and chile pepper (Capsicum annum L.). Minimal intact PCP was detected in the fescue and lettuce by gas chromatography/mass spectrometry (GC/MS) analysis. No intact PCP was detected in the carrot tissue extracts. Chile pepper was not analyzed for intact PCP because methylene chloride extracts contained minimal {sup 14}C. The GC/MS analysis of soil extracts at harvest suggests a half-life of PCP of about 10 d independent ofmore » sludge rate or PCP loading rate. Rapid degradation of PCP in the soil apparently limited PCP availability to the plant. Bioconcentration factors (dry plant wt./initial soil PCP concentration) based on intact PCP were < 0.01 for all crops, suggesting little PCP uptake. Thus, food-chain crop PCP uptake in these alkaline soils should not limit land application of sludge.« less

Alternative initial proton acceptors for the D pathway of Rhodobacter sphaeroides cytochrome c oxidase

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan

2011-01-01

In order to characterize protein structures that control proton uptake, forms of cytochrome c oxidase (CcO) containing a carboxyl or a thiol group in line with the initial, internal waters of the D pathway for proton transfer have been assayed in the presence and absence of subunit III. Subunit III provides approximately half of the protein surrounding the entry region of the D pathway. The mutant N139D-D132N contains a carboxyl group 6Å within the D pathway and lacks the normal, surface-exposed proton acceptor, Asp-132. With subunit III, the steady-state activity of this mutant is slow but once subunit III is removed its activity is the same as wild-type CcO lacking subunit III (∼1800 H+ s-1). Thus, a carboxyl group ∼25% within the pathway enhances proton uptake even though the carboxyl has no direct contact with bulk solvent. Protons from solvent apparently move to internal Asp-139 through a short file of waters, normally blocked by subunit III. Cysteine-139 also supports rapid steady-state proton uptake, demonstrating that an anion other than a carboxyl can attract and transfer protons into the D pathway. When both Asp-132 and Asp/Cys-139 are present, the removal of subunit III increases CcO activity to rates greater than that of normal CcO due to simultaneous proton uptake by two initial acceptors. The results show how the environment of the initial proton acceptor for the D pathway in these CcO forms dictates the pH range of CcO activity, with implications for the function of Asp-132, the normal proton acceptor. PMID:21344856

Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

PubMed

Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

2012-04-15

A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in <1 min and initial rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together, these results suggest that L-FABP, particularly in the absence of SCP-2, plays a significant role in HDL-mediated cholesterol uptake in cultured primary hepatocytes.

Everolimus induces rapid plasma glucose normalization in insulinoma patients by effects on tumor as well as normal tissues.

PubMed

Fiebrich, Helle-Brit; Siemerink, Ester J M; Brouwers, Adrienne H; Links, Thera P; Remkes, Wouter S; Hospers, Geke A P; de Vries, Elisabeth G E

2011-01-01

Mammalian target of rapamycin inhibitor everolimus administered to four insulinoma patients rapidly controlled hypoglycemia (Kulke et al., N Engl J Med 2009;360:195-197). We wanted to identify the kinetics of everolimus effects on controlling hypoglycemia and understand underlying mechanisms. Three consecutive patients with a metastasized symptomatic insulinoma were started on 100 μg of octreotide subcutaneously three times daily. Because of persisting hypoglycemias, treatment with daily 10 mg of oral everolimus was initiated. Serial plasma glucose levels and serum insulin levels were measured. Computer tomography (CT) scans were performed before and after 2 and 5 months of treatment. [¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) scans, to visualize glucose metabolism, were made before and after 2 weeks, 5 weeks, and 5 months of treatment. The ¹⁸F-FDG uptake was quantified as the maximum standardized uptake value. All patients achieved control of hypoglycemia on everolimus within 14 days. Insulin levels were 2.5- to 6.3-fold elevated before start of treatment and declined 14%-64% after 4 weeks of treatment. CT scans showed stable disease at 2 months in all patients, with progressive disease after 5 months in one. Before treatment, both the tumor lesions and the muscles and myocardium showed high ¹⁸F-FDG uptake. Everolimus reduced tumor and muscle ¹⁸F-FDG uptake after 2 weeks by 26% ± 14% and 19% ± 41%, and after 5 months by 31% ± 13% and 27% ± 41%. Everolimus normalizes plasma glucose levels in metastatic insulinoma within 14 days, coinciding with a lower glucose uptake in tumor and muscles and declining (pro)insulin levels. This effect on tumor as well as normal tissues explains the rapid controlling of hypoglycemia.

The contribution of water soluble and water insoluble organic fractions to oxygen uptake rate during high rate composting.

PubMed

Giuliana, D'Imporzano; Fabrizio, Adani

2007-02-01

This study aims to establish the contribution of the water soluble and water insoluble organic fractions to total oxygen uptake rate during high rate composting process of a mixture of organic fraction of municipal solid waste and lignocellulosic material. This mixture was composted using a 20 l self-heating pilot scale composter for 250 h. The composter was fully equipped to record both the biomass-temperature and oxygen uptake rate. Representative compost samples were taken at 0, 70, 100, 110, 160, and 250 h from starting time. Compost samples were fractionated in water soluble and water insoluble fractions. The water soluble fraction was then fractionated in hydrophilic, hydrophobic, and neutral hydrophobic fractions. Each fraction was then studied using quantitative (total organic carbon) and qualitative analysis (diffuse reflectance infrared spectroscopy and biodegradability test). Oxygen uptake rates were high during the initial stages of the process due to rapid degradation of the soluble degradable organic fraction (hydrophilic plus hydrophobic fractions). Once this fraction was depleted, polymer hydrolysis accounted for most of the oxygen uptake rate. Finally, oxygen uptake rate could be modeled using a two term kinetic. The first term provides the oxygen uptake rate resulting from the microbial growth kinetic type on easily available, no-limiting substrate (soluble fraction), while the second term considers the oxygen uptake rate caused by the degradation of substrate produced by polymer hydrolysis.

Identifying metastatic breast tumors using textural kinetic features of a contrast based habitat in DCE-MRI

NASA Astrophysics Data System (ADS)

Chaudhury, Baishali; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Drukteinis, Jennifer S.

2015-03-01

The ability to identify aggressive tumors from indolent tumors using quantitative analysis on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) would dramatically change the breast cancer treatment paradigm. With this prognostic information, patients with aggressive tumors that have the ability to spread to distant sites outside of the breast could be selected for more aggressive treatment and surveillance regimens. Conversely, patients with tumors that do not have the propensity to metastasize could be treated less aggressively, avoiding some of the morbidity associated with surgery, radiation and chemotherapy. We propose a computer aided detection framework to determine which breast cancers will metastasize to the loco-regional lymph nodes as well as which tumors will eventually go on to develop distant metastses using quantitative image analysis and radiomics. We defined a new contrast based tumor habitat and analyzed textural kinetic features from this habitat for classification purposes. The proposed tumor habitat, which we call combined-habitat, is derived from the intersection of two individual tumor sub-regions: one that exhibits rapid initial contrast uptake and the other that exhibits rapid delayed contrast washout. Hence the combined-habitat represents the tumor sub-region within which the pixels undergo both rapid initial uptake and rapid delayed washout. We analyzed a dataset of twenty-seven representative two dimensional (2D) images from volumetric DCE-MRI of breast tumors, for classification of tumors with no lymph nodes from tumors with positive number of axillary lymph nodes. For this classification an accuracy of 88.9% was achieved. Twenty of the twenty-seven patients were analyzed for classification of distant metastatic tumors from indolent cancers (tumors with no lymph nodes), for which the accuracy was 84.3%.

Uptake of perfluorinated compounds by plants grown in nutrient solution.

PubMed

García-Valcárcel, A I; Molero, E; Escorial, M C; Chueca, M C; Tadeo, J L

2014-02-15

The uptake rates of three perfluorinated carboxylates and three perfluorinated sufonates by a grass (B diandrus) grown in nutrient solution at two different perfluorinated compounds (PFCs) concentrations were assessed. Grass can be ingested by grazing animals causing the PFCs to enter the food chain, which is a pathway of human exposure to these compounds. A rapid and miniaturized method was developed to determine PFCs in plants, based on a matrix solid-phase dispersion (MSPD) extraction procedure followed by quantitation by HPLC-MS/MS with an MQL in the range from 1 to 9 ng/g. An increase of PFCs levels in plant was observed along the exposure time. Differences in uptake for studied perfluorinated carboxylates were found, showing a decrease with carbon chain length (from 3027 to 1,167 ng/g at the end of assay), whereas no significant differences in absorption were obtained between perfluorinated sulfonates (about 1,700 ng/g). Initially, higher PFC transfer factors (ratio between concentration in plant and concentration in initial nutrient solution) were obtained for plants growing in the nutrient solution at the highest PFC concentration, but these factors became similar with time to plants exposed to the lowest concentration. © 2013 Elsevier B.V. All rights reserved.

Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.

PubMed

Aubert, Agnès; Costalat, Robert; Magistretti, Pierre J; Pellerin, Luc

2005-11-08

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans.

Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation

PubMed Central

Aubert, Agnès; Costalat, Robert; Magistretti, Pierre J.; Pellerin, Luc

2005-01-01

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans. PMID:16260743

Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

PubMed

Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

2016-05-05

High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Oncogene pathway activation in mammary tumors dictates [18F]-FDG-PET uptake

PubMed Central

Alvarez, James V.; Belka, George K.; Pan, Tien-chi; Chen, Chien-Chung; Blankemeyer, Eric; Alavi, Abass; Karp, Joel; Chodosh, Lewis A.

2015-01-01

Increased glucose utilization is a hallmark of human cancer that is used to image tumors clinically. In this widely used application, glucose uptake by tumors is monitored by positron emission tomography (PET) of the labeled glucose analog F-18-2-fluoro-2-deoxyglucose (18F-FDG). Despite its widespread clinical use, the cellular and molecular mechanisms that determine FDG uptake - a tool that can monitor tumor heterogeneity - remain poorly understood. In this study, we compared FDG uptake in mammary tumors driven by the Akt1, c-MYC, HER2/neu, Wnt1 or H-Ras oncogenes in genetically engineered mice, correlating it to tumor growth, cell proliferation and levels of gene expression involved in key steps of glycolytic metabolism. We found that FDG uptake by tumors was dictated principally by the driver oncogene and was not independently associated with tumor growth or cellular proliferation. Oncogene downregulation resulted in a rapid decrease in FDG uptake, preceding effects on tumor regression, irrespective of the baseline level of uptake. FDG uptake correlated positively with expression of hexokinase-2 (HK2) and HIF-1α and associated negatively with PFK-2b expression and p-AMPK. The correlation of HK2 and FDG uptake was independent of all variables tested, including the initiating oncogene, suggesting that HK2 is an independent predictor of FDG uptake. In contrast, expression of Glut1 was correlated with FDG uptake only in tumors driven by Akt or HER2/neu. Together, these results showed that the oncogenic pathway activated within a tumor is a primary determinant of its FDG uptake, mediated by key glycolytic enzymes that provide a framework to interpret effects on this key parameter in clinical imaging. PMID:25239452

A policy framework for accelerating adoption of new vaccines

PubMed Central

Hajjeh, Rana; Wecker, John; Cherian, Thomas; O'Brien, Katherine L; Knoll, Maria Deloria; Privor-Dumm, Lois; Kvist, Hans; Nanni, Angeline; Bear, Allyson P; Santosham, Mathuram

2010-01-01

Rapid uptake of new vaccines can improve health and wealth and contribute to meeting Millennium Development Goals. In the past, however, the introduction and use of new vaccines has been characterized by delayed uptake in the countries where the need is greatest. Based on experience with accelerating the adoption of Hib, pneumococcal and rotavirus vaccines, we propose here a framework for new vaccine adoption that may be useful for future efforts. The framework organizes the major steps in the process into a continuum from evidence to policy, implementation and finally access. It highlights the important roles of different actors at various times in the process and may allow new vaccine initiatives to save time and improve their efficiency by anticipating key steps and actions. PMID:21150269

A policy framework for accelerating adoption of new vaccines.

PubMed

Levine, Orin S; Hajjeh, Rana; Wecker, John; Cherian, Thomas; O'Brien, Katherine L; Knoll, Maria Deloria; Privor-Dumm, Lois; Kvist, Hans; Nanni, Angeline; Bear, Allyson P; Santosham, Mathuram

2010-12-01

Rapid uptake of new vaccines can improve health and wealth and contribute to meeting Millennium Development Goals. In the past, however, the introduction and use of new vaccines has been characterized by delayed uptake in the countries where the need is greatest. Based on experience with accelerating the adoption of Hib, pneumococcal and rotavirus vaccines, we propose here a framework for new vaccine adoption that may be useful for future efforts. The framework organizes the major steps in the process into a continuum from evidence to policy, implementation and finally access. It highlights the important roles of different actors at various times in the process and may allow new vaccine initiatives to save time and improve their efficiency by anticipating key steps and actions.

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals*

PubMed Central

Daniels, Isadora Susan; Zhang, Jianfa; O'Brien, William G.; Tao, Zhenyin; Miki, Tomoko; Zhao, Zhaoyang; Blackburn, Michael R.; Lee, Cheng Chi

2010-01-01

Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5′-AMP uptake by erythrocytes. Wild type, ecto-5′-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5′-AMP-induced hypometabolism in a similar fashion. Injection of 5′-AMP leads to two distinct declining phases of oxygen consumption (VO2). The phase I response displays a rapid and steep decline in VO2 that is independent of body temperature (Tb) and ambient temperature (Ta). It is followed by a phase II decline that is linked to Tb and moderated by Ta. Altering the dosages of 5′-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a Ta of 15 °C is effective for induction of DH with the appropriate dose of 5′-AMP. Erythrocyte uptake of 5′-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5′-AMP administration and is in parallel with the phase I decline in VO2. In summary, our investigations reveal that 5′-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5′-AMP. PMID:20430891

A role of erythrocytes in adenosine monophosphate initiation of hypometabolism in mammals.

PubMed

Daniels, Isadora Susan; Zhang, Jianfa; O'Brien, William G; Tao, Zhenyin; Miki, Tomoko; Zhao, Zhaoyang; Blackburn, Michael R; Lee, Cheng Chi

2010-07-02

Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5'-AMP uptake by erythrocytes. Wild type, ecto-5'-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5'-AMP-induced hypometabolism in a similar fashion. Injection of 5'-AMP leads to two distinct declining phases of oxygen consumption (VO(2)). The phase I response displays a rapid and steep decline in VO(2) that is independent of body temperature (T(b)) and ambient temperature (T(a)). It is followed by a phase II decline that is linked to T(b) and moderated by T(a). Altering the dosages of 5'-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a T(a) of 15 degrees C is effective for induction of DH with the appropriate dose of 5'-AMP. Erythrocyte uptake of 5'-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5'-AMP administration and is in parallel with the phase I decline in VO(2). In summary, our investigations reveal that 5'-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5'-AMP.

Comparative Studies on the Toxicokinetics of Benzo[a]pyrene in Pinctada martensii and Perna viridis.

PubMed

Wang, Haihua; Cui, Lili; Cheng, Huamin; Zhang, Yu; Diao, Xiaoping; Wang, Jun

2017-05-01

Research on the kinetics of Benzo[a]pyrene (B[a]P) bioaccumulation in the clam Pinctada martensii and mussel Perna viridis showed that the initial rate of uptake was directly related to the PAH concentrations in the ambient environment. The uptake and depuration rate constants were different at the four B[a]P exposure levels, which indicated that the toxicokinetic rate constants mainly depended on the exposure levels of pollutants to the environment. In addition, the uptake rate constants of B[a]P were higher than the depuration rate constants in the entire experiment. The comparison demonstrated that mussels release B[a]P more rapidly than clams. The bioconcentration factors (BCFs) of B[a]P varied from 3335 to 12892 in the clam and 2373-6235 in the mussel. These findings on the bioaccumulation kinetics for petroleum hydrocarbons, in association with the critical body residue, will be valuable when choosing sensitive organisms to assess the potential ecotoxicological risk to the marine environment.

Rapid Review Summit: an overview and initiation of a research agenda.

PubMed

Polisena, Julie; Garritty, Chantelle; Umscheid, Craig A; Kamel, Chris; Samra, Kevin; Smith, Jeannette; Vosilla, Ann

2015-09-26

The demand for accelerated forms of evidence synthesis is on the rise, largely in response to requests by health care decision makers for expeditious assessment and up-to-date information about health care technologies and health services and programs. As a field, rapid review evidence synthesis is marked by a tension between the strategic priority to inform health care decision-making and the scientific imperative to produce robust, high-quality research that soundly supports health policy and practice. In early 2015, the Canadian Agency for Drugs and Technologies in Health convened a forum in partnership with the British Columbia Ministry of Health, the British Columbia Centre for Clinical Epidemiology and Evaluation, the Ottawa Hospital Research Institute, and the University of Pennsylvania. More than 150 evidence synthesis producers and end users attended the Rapid Review Summit: Then, Now and in the Future. The Summit program focused on the evolving role and practices of rapid reviews to support informed health care policy and clinical decision-making, including the uptake and use of health technology assessment. Our discussion paper highlights the important discussions that occurred during the Rapid Review Summit. It focuses on the initial development of a research agenda that resulted from the Summit presentations and discussions. The research topics centered on three key areas of interest: (1) how to conduct a rapid review; (2) investigating the validity and utility of rapid reviews; and (3) how to improve access to rapid reviews.

Pharmacy-based interventions for initiating effective contraception following the use of emergency contraception: a pilot study.

PubMed

Michie, L; Cameron, S T; Glasier, A; Larke, N; Muir, A; Lorimer, A

2014-10-01

In Scotland most women get emergency contraception (EC) from pharmacies. Pharmacists currently cannot provide effective ongoing contraception after EC. In this pilot study, we aimed to determine the feasibility of a larger study designed to ascertain if pharmacy-based interventions can increase the uptake of effective contraception after EC. This is a pilot study of women presenting for levonorgestrel EC to community pharmacies in Edinburgh, UK, in 2012. Pharmacies were cluster randomized to provide either standard care or one of two interventions: (a) one packet of progestogen-only pills (POPs), giving women 1 month to arrange ongoing contraception; (b) invitation to present the empty EC packet to a family planning clinic (FPC) for contraceptive advice (rapid access). One hundred sixty-eight women were recruited from 11 pharmacies to POP (n=56), rapid access (n=58) and standard care (N=54) groups, respectively. Telephone follow-up was conducted successfully in 102 women (61%) 6-8 weeks later to determine current contraceptive use. In the POP arm, 35/39 (90%) women used the pills provided, and 9/28 women (32%) in the rapid access arm attended the FPC. The proportion of women using effective contraception at follow-up was significantly greater in both POP [56% (22/39), p=<0.001] and rapid access [52% (13/25), p=0.006] groups compared to standard care [16% (5/31)]. The relative probability of a woman using an effective method of contraception versus barrier/no method, after use of EC, was 3.13 [95% confidence interval (CI), 1.90-5.13] in the POP group and 2.57 (95% CI, 1.55-4.27) in the rapid access group. This promising pilot study suggests that simple pharmacy-based interventions may increase the uptake of effective contraception after EC. A larger study is required to provide further validation of these findings. For women obtaining EC from a pharmacy, simple interventions such as supplying 1 month of a POP, or offering rapid access to a FPC, hold promise as strategies to increase the uptake of effective contraception after EC. Copyright © 2014 Elsevier Inc. All rights reserved.

Trends in ART Initiation among Men and Non-Pregnant/Non-Breastfeeding Women before and after Option B+ in Southern Malawi

PubMed Central

Yeatman, Sara; van Oosterhout, Joep J.; Chan, Adrienne; Mantengeni, Alfred; Landes, Megan; Bedell, Richard; Kawalazira, Gift; Sodhi, Sumeet

2016-01-01

Background Option B+ is promoted as a key component to eliminating vertical transmission of HIV; however, little is known about the policy’s impact on non-targeted populations, such as men and non-pregnant/non-breastfeeding women. We compare ART uptake among non-targeted populations during pre/post Option B+ periods in Zomba District, Malawi. Methods Individual-level ART registry data from 27 health facilities were digitized and new ART initiates were disaggregated by sex and type of initiate (Option B+ or not). Data were analyzed over the pre- (January 2009-June 2011) and post- (July 2011- December 2013) Option B+ periods. Results After the implementation of Option B+, the total number of new female initiates increased significantly (quarterly median: 547 vs. 816; P = 0.001) and their median age decreased from 34 to 31 years (P = <0.001). Both changes were the result of the rapid and sustained uptake of ART among Option B+ clients. Post-policy, Option B+ clients represented 48% of all new female initiates while the number of females who initiated through CD4 or WHO staging criteria significantly decreased (quarterly median: 547 vs. 419; P = 0.005). The number and age of male initiates remained stable; however, the proportion of men among new initiates decreased (36% vs. 31%; P = <0.001). Conclusions Option B+ shifted the profile of first-time initiates towards younger and fertile women. Declines among non-Option B+ women most likely reflect earlier initiation during pregnancies before deteriorations in health. The decreased proportion of men among first-time initiates represents a growing gender disparity in HIV services that deserves immediate attention. PMID:28002413

Trends in ART Initiation among Men and Non-Pregnant/Non-Breastfeeding Women before and after Option B+ in Southern Malawi.

PubMed

Dovel, Kathryn; Yeatman, Sara; van Oosterhout, Joep J; Chan, Adrienne; Mantengeni, Alfred; Landes, Megan; Bedell, Richard; Kawalazira, Gift; Sodhi, Sumeet

2016-01-01

Option B+ is promoted as a key component to eliminating vertical transmission of HIV; however, little is known about the policy's impact on non-targeted populations, such as men and non-pregnant/non-breastfeeding women. We compare ART uptake among non-targeted populations during pre/post Option B+ periods in Zomba District, Malawi. Individual-level ART registry data from 27 health facilities were digitized and new ART initiates were disaggregated by sex and type of initiate (Option B+ or not). Data were analyzed over the pre- (January 2009-June 2011) and post- (July 2011- December 2013) Option B+ periods. After the implementation of Option B+, the total number of new female initiates increased significantly (quarterly median: 547 vs. 816; P = 0.001) and their median age decreased from 34 to 31 years (P = <0.001). Both changes were the result of the rapid and sustained uptake of ART among Option B+ clients. Post-policy, Option B+ clients represented 48% of all new female initiates while the number of females who initiated through CD4 or WHO staging criteria significantly decreased (quarterly median: 547 vs. 419; P = 0.005). The number and age of male initiates remained stable; however, the proportion of men among new initiates decreased (36% vs. 31%; P = <0.001). Option B+ shifted the profile of first-time initiates towards younger and fertile women. Declines among non-Option B+ women most likely reflect earlier initiation during pregnancies before deteriorations in health. The decreased proportion of men among first-time initiates represents a growing gender disparity in HIV services that deserves immediate attention.

Enhancement of Cell Membrane Invaginations, Vesiculation and Uptake of Macromolecules by Protonation of the Cell Surface

PubMed Central

Ben-Dov, Nadav; Korenstein, Rafi

2012-01-01

The different pathways of endocytosis share an initial step involving local inward curvature of the cell’s lipid bilayer. It has been shown that to generate membrane curvature, proteins or lipids enforce transversal asymmetry of the plasma membrane. Thus it emerges as a general phenomenon that transversal membrane asymmetry is the common required element for the formation of membrane curvature. The present study demonstrates that elevating proton concentration at the cell surface stimulates the formation of membrane invaginations and vesiculation accompanied by efficient uptake of macromolecules (Dextran-FITC, 70 kD), relative to the constitutive one. The insensitivity of proton induced uptake to inhibiting treatments and agents of the known endocytic pathways suggests the entry of macromolecules to proceeds via a yet undefined route. This is in line with the fact that neither ATP depletion, nor the lowering of temperature, abolishes the uptake process. In addition, fusion mechanism such as associated with low pH uptake of toxins and viral proteins can be disregarded by employing the polysaccharide dextran as the uptake molecule. The proton induced uptake increases linearly in the extracellular pH range of 6.5 to 4.5, and possesses a steep increase at the range of 4> pH>3, reaching a plateau at pH≤3. The kinetics of the uptake implies that the induced vesicles release their content to the cytosol and undergo rapid recycling to the plasma membrane. We suggest that protonation of the cell’s surface induces local charge asymmetries across the cell membrane bilayer, inducing inward curvature of the cell membrane and consequent vesiculation and uptake. PMID:22558127

RAPID NITRATE UPTAKE RATES AND LARGE SHORT-TERM STORAGE CAPACITIES MAY EXPLAIN WHY OPPORTUNISTIC GREEN MACROALGAE DOMINATE SHALLOW EUTROPHIC ESTUARIES1.

PubMed

Kennison, Rachel L; Kamer, Krista; Fong, Peggy

2011-06-01

We quantified the effects of initial macroalgal tissue nitrogen (N) status (depleted and enriched) and varying pulses of nitrate (NO 3 - ) concentration on uptake and storage of nitrogen in Ulva intestinalis L. and Ulva expansa (Setch.) Setch. et N. L. Gardner using mesocosms modeling shallow coastal estuaries in Mediterranean climates. Uptake of NO 3 - (μmol · g dry weight [dwt] -1  · h -1 ) was measured as loss from the water after 1, 2, 4, 8, 12, and 24 h and storage as total tissue nitrogen (% dwt) and nitrate (ppm). Both species of algae exhibited a high affinity for NO 3 - across all N pulses and initial tissue contents. There was greater NO 3 - removal from the water for depleted than enriched algae across all time intervals. In the low-N-pulse treatment, U. intestinalis and U. expansa removed all measurable NO 3 - within 8 and 12 h, respectively, and in the medium and high treatments, removal was high and then decreased over time. Maximum mean uptake rates of nitrate were greater for U. expansa (∼300 μmol · g dwt -1  · h -1 ) than U. intestinalis (∼100 μmol · g dwt -1  · h -1 ); however, uptake rates were highly variable over time. Overall, U. expansa uptake rates were double those of U. intestinalis. Maximum tissue NO 3 - for U. expansa was >1,000 ppm, five times that of U. intestinalis, suggesting that U. expansa has a greater storage capacity in this cellular pool. These results showed that opportunistic green algae with differing tissue nutrient histories were able to efficiently remove nitrate from the water across a wide range of N pulses; thus, both are highly adapted to proliferate in estuarine environments with pulsed nutrient supplies. © 2011 Phycological Society of America.

Surface chemistry of ferrihydrite: Part 2. Kinetics of arsenate adsorption and coprecipitation

USGS Publications Warehouse

Fuller, C.C.; Dadis, J.A.; Waychunas, G.A.

1993-01-01

The kinetics of As(V) adsorption by ferrihydrite was investigated in coprecipitation and postsynthesis adsorption experiments conducted in the pH range 7.5-9.0. In coprecipitation experiments, As(V) was present in solution during the hydrolysis and precipitation of iron. In adsorption experiments, a period of rapid (<5 min) As(V) uptake from solution was followed by continued uptake for at least eight days, as As(V) diffused to adsorption sites on ferrihydrite surfaces within aggregates of colloidal particles. The time dependence of As(V) adsorption is well described by a general model for diffusion into a sphere if a subset of surface sites located near the exterior of aggregates is assumed to attain adsorptive equilibrium rapidly. The kinetics of As(V) desorption after an increase in pH were also consistent with diffusion as a rate-limiting process. Aging of pure ferrihydrite prior to As(V) adsorption caused a decrease in adsorption sites on the precipitate owing to crystallite growth. In coprecipitation experiments, the initial As(V) uptake was significantly greater than in post-synthesis adsorption experiments, and the rate of uptake was not diffusion limited because As(V) was coordinated by surface sites before crystallite growth and coagulation processes could proceed. After the initial adsorption, As(V) was slowly released from coprecipitates for at least one month, as crystallite growth caused desorption of As(V). Adsorption densities as high as 0.7 mole As(V) per mole of Fe were measured in coprecipitates, in comparison to 0.25 mole As(V) per mole of Fe in post-synthesis adsorption experiments. Despite the high Concentration of As(V) in the precipitates, EXAFS spectroscopy (Waychunas et al., 1993) showed that neither ferric arsenate nor any other As-bearing surface precipitate or solid solution was formed. The high adsorption densities are possible because the ferrihydrite particles are extremely small, approaching the size of small dioctahedral chains at the highest As(V) adsorption density. The results suggest that the solid solution model proposed by Fox (1989, 1992) for control of arsenate and phosphate concentrations in natural waters may be invalid. ?? 1993.

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

Šefl, Martin, E-mail: martin.sefl@gmail.com; Kyriakou, Ioanna; Emfietzoglou, Dimitris, E-mail: demfietz@cc.uoi.gr

Purpose: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. Methods: The instantaneous-uptake model of O’Donoghue [“The impact of tumor cell proliferation in radioimmunotherapy,” Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). Results: Surviving fractions aremore » calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h{sup −1}, and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy{sup −1}. It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. Conclusions: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.« less

Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

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

Hand, W.L.; King-Thompson, N.L.

Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat lessmore » than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes.« less

Nano modification of NZVI with an aquatic plant Azolla filiculoides to remove Pb(II) and Hg(II) from water: Aging time and mechanism study.

PubMed

Arshadi, M; Abdolmaleki, M K; Mousavinia, F; Foroughifard, S; Karimzadeh, A

2017-01-15

This paper reports the preparation and stabilization of nano zero valent iron (NZVI) on a modified aquatic plant, Azolla filiculoides, and investigates its potential for the adsorption/reduction of Pb(II) and Hg(II) ions from aqueous media even after six months of storage in the lab condition. XRD, TEM and zeta potential results demonstrated that the Azolla-NaOH could be a good stabilizer of aged NZVI (six months) and the green support suppressed the oxidation and aggregation of immobilized NZVI. Kinetic and equilibrium models for lead and mercury ions uptake were developed by considering the effect of the initial Pb(II) and Hg(II) concentrations, contact time, adsorbent dosage, initial pH and effect of temperature. The contact time to obtain equilibrium for maximum uptake by Azolla-OH-NZVI was 20min. The removal of toxic metal ions has been monitored in terms of pseudo-first- and -second-order kinetics, and the Freundlich and Langmuir isotherms models have also been utilized to the equilibrium uptake results. The uptake kinetics followed the mechanism of the pseudo-second-order equation for all systems studied, confirming chemical sorption as the rate-limiting step of adsorption mechanisms and not involving a mass transfer in solution. The thermodynamic results confirmed that the uptake of Pb(II) and Hg(II) ions were feasible, spontaneous and endothermic at 25-80°C. XRD and zeta potential data displayed the existence of Pb(0) and Hg(0) on the Azolla-OH-NZVI surface. The nanobioadsorbent revealed high recyclability due to its reasonable uptake efficiency after 7th adsorption-desorption cycles. The proposed nano biocomposite could also be utilized to uptake Pb(II) and Hg(II) ions from the real water (Anzali lagoon water). However, coated NZVI with Azolla filiculoides as a green and environmentally friendly support suppressed rapid oxidation and aggregation of the immobilized NZVI, therefore vastly enhancing the probability of environmental transport and reducing the sedimentation and potential for toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Uptake, biotransformation, and elimination of benzo[a]pyrene by the gammarid amphipod, Leptocheirus plumulosus

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

Dickbut, R.M.; Huszai, C.M.; Lay, P.W.

1995-12-31

The uptake, biotransformation, and elimination of {sup 3}H-benzo[a]pyrene (B[a]P) by the gammarid amphipod Leptocheirus plumulosus was evaluated in laboratory exposures. Rapid uptake (i.e. within 2.5 h) of sediment-associated B[a]P was observed, and during the exposures organism body burdens were dominated by organic extractable (e.g. parent compound) components, with aqueous soluble and bound metabolites constituting a much smaller fraction of the total body burden. However, upon discontinuation of exposure of the organisms to B[a]P, organic extractable compounds were more rapidly eliminated by L. plumulosus than the aqueous extractable and bound contaminant pools. Uptake and elimination of B[a]P were adequately modeled assumingmore » first order kinetics, with the exception of the early stages of exposure. The rapid uptake during the first few hours of exposure of Leptocheirus to sediment-associated B[a]P may be due to sorption of B[a]P to the exoskeleton of the organism. This hypothesis is under further investigation. Uptake and elimination of B[a]P metabolite pools by L. plumulosus was best modeled assuming a fraction of the metabolite pool was irreversibly bound or slowly eliminated.« less

Studies on the uptake of fatty acids by brush border membranes of the rabbit intestine.

PubMed

Proulx, P; Aubry, H; Brglez, I; Williamson, D G

1985-04-01

Initial studies revealed that the uptake of palmitic acid and oleic acid into brush border membranes was similar when these were isolated from either whole small intestine, jejunum, or ileum. The uptake of these fatty acids was somewhat lower with membranes obtained from duodenum. Subsequent studies, all with membranes obtained from whole intestine, indicated an increase in binding with chain length of fatty acid of up to 16 carbons. Unsaturation decreased this uptake somewhat. Taurocholate and 1-palmitoyl lysolecithin had a moderate stimulatory effect on the binding of oleic acid and palmitic acid at concentrations of 10 and 0.5 mM, respectively, and inhibited at higher concentrations. Addition of 1.4 mM egg lecithin to the fatty acid - bile salt micelles, such that the lecithin - bile salt ratio was 0.2, decreased the uptake of fatty acids generally, but did not significantly affect the pattern of binding by membrane fractions isolated from different segments nor did it change the pattern of labelling when fatty acid chain length and unsaturation were varied. At lower concentrations, egg lecithin had little effect on the uptake of oleic acid, whereas dipalmitoyl phosphatidylcholine stimulated binding of both palmitic acid and oleic acid over the entire range of concentrations tested. Preincubation of the membranes with this saturated phospholipid stimulated the uptake of oleic acid, and addition of this choline lipid to the oleic acid - bile salt containing micelles did not substantially enhance fatty acid uptake in lipid-treated membranes. The binding of fatty acid was very rapid either in the presence or the absence of Ca2+, such that even in zero-time controls essentially equilibrium bindings were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a zinc/proton antiporter in rat brain.

PubMed

Colvin, R A; Davis, N; Nipper, R W; Carter, P A

2000-05-01

The data presented in this paper are consistent with the existence of a plasma membrane zinc/proton antiport activity in rat brain. Experiments were performed using purified plasma membrane vesicles isolated from whole rat brain. Incubating vesicles in the presence of various concentrations of 65Zn2+ resulted in a rapid accumulation of 65Zn2+. Hill plot analysis demonstrated a lack of cooperativity in zinc activation of 65Zn2+ uptake. Zinc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or CO2+. Calcium (1 mM) was less effective at inhibiting 65Zn2+ uptake and Mg2+ and Mn2+ had no effect. The initial rate of vesicular 65Zn2+ uptake was inhibited by increasing extravesicular H+ concentration. Vesicles preloaded with 65Zn2+ could be induced to release 65Zn2+ by increasing extravesicular H+ or addition of 1 mM nonradioactive Zn2+. Hill plot analysis showed a lack of cooperativity in H+ activation of 65Zn2+ release. Based on the Hill analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange and Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribute to the reuptake of zinc to replenish presynaptic vesicle stores after stimulation.

Development of a Hydrogen Uptake-Release Mg-Based Alloy by Adding a Polymer CMC (Carboxymethylcellulose, Sodium Salt) via Reaction-Accompanying Milling

NASA Astrophysics Data System (ADS)

Kwak, Young Jun; Choi, Eunho; Song, Myoung Youp

2018-03-01

The addition of carboxymethylcellulose, sodium salt (CMC) might improve the hydrogen uptake and release properties of Mg since it has a relatively low melting point and the melting of CMC during milling in hydrogen (reaction-accompanying milling) may make the milled samples be in good states to absorb and release hydrogen rapidly and to have a large hydrogen-storage capacity. Samples with compositions of 95 w/o Mg + 5 w/o CMC (named Mg-5CMC) and 90 w/o Mg + 10 w/o CMC (named Mg-10CMC) were prepared by adding CMC via reaction-accompanying milling. Activation of Mg-10CMC was completed after about 3 hydrogen uptake-release cycles. Mg-10CMC had a higher initial hydrogen uptake rate and a larger amount of hydrogen absorbed in 60 min, U (60 min), than Mg-5CMC before and after activation. At the cycle number of three (CN = 3), Mg-10CMC had a very high initial hydrogen uptake rate (1.56 w/o H/min) and a large U (60 min) (5.57 w/o H) at 593 K in hydrogen of 12 bar, showing that the activated Mg-10CMC has an effective hydrogen-storage capacity of about 5.6 w/o at 593 K in hydrogen of 12 bar at CN = 3. At CN = 2, Mg-10CMC released 1.00 w/o H in 2.5 min, 4.67 w/o H in 10 min, and 4.76 w/o H in 60 min at 648 K in hydrogen of 1.0 bar. The milling in hydrogen of Mg with CMC is believed to generate imperfections and cracks and reduce the particle size. The addition of 10 w/o CMC was more effective on the initial hydrogen uptake rate and U (60 min) compared with the 10 w/o additions of NbF5, TaF5, Fe2O3, and MnO, and the 10 w/o simultaneous addition of Ni, Fe, and Ti. To the best of our knowledge, this study is the first in which a polymer CMC is added to Mg by reaction-accompanying milling to improve the hydrogen storage properties of Mg.

Biosorption of inorganic tin and methyltin compounds by estuarine macroalgae

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

Wright, P.J.; Weber, J.H.

1991-02-01

Biosorption kinetics of total recoverable inorganic tin (TRISn), MeSn{sup 3+}, Me{sub 2}Sn{sup 2+}, and Me{sub 3}Sn{sup +} compounds onto tissue from the macroalga Fucus vesiculosus and onto a mixed community of Enteromorpha spp. (a filamentous genus) showed that after 48-h accumulation of tin compounds followed the trend TRISn {approximately} MeSn{sup 3+} > Me{sub 2}Sn{sup 2+} > Me{sub 3}Sn{sup +}. Uptake of tin compounds onto F. vesiculosus consisted of three phases: rapid phase 1, intermediate phase 2 (modeled by first-order kinetics). Uptake of tin compounds by Enteromorpha spp. occurred in rapid phase 1 and intermediate, saturating phase 2, which was completemore » in 3 h for TRISn and MeSn{sup 3+} and in 18 h for Me{sub 2}Sn{sup 2+} and Me{sub 2}Sn{sup 2+} and Me{sub 3}Sn{sup +}. After 24 h, (TRISn) and (MeSn{sup 3+}) in dark-incubated plants, suggesting active uptake processes during phase 3. Enteromorpha spp. incubated in the dark for 1 h contained significantly less TRISn and MeSn{sup 3+}, but not less Me{sub 2}Sn{sup 2+} and Me{sub 3}Sn{sup +}, than light-incubated plants. Interactions with different compartments of the algal thallus account for differences in amounts of biosorbed tin compounds. Initial phase 1 biosorption by both algae was probably adsorption onto the thallus surface.« less

Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart.

PubMed Central

Mann, G E; Yudilevich, D L

1984-01-01

Capillary permeability and cellular uptake of noradrenaline by the isolated artificially perfused rabbit heart was measured using rapid (less than 30 s) single-circulation tracer-dilution techniques. In a single coronary circulation capillary extractions of L-[14C]noradrenaline and D-[3H]mannitol (extracellular reference) relative to an intravascular marker, 125I-labelled albumin, were similar and above 60%. The 'apparent' volume of distribution for tracer noradrenaline was 2.5-fold larger than that measured for D-mannitol (0.32 ml g-1) suggesting cellular uptake of the amine. Unidirectional noradrenaline uptake was estimated by directly comparing coronary sinus dilution profiles of L-[3H]noradrenaline and D-[14C]mannitol. Michaelis-Menten saturation kinetics based on a single-entry system were determined (Km = 2.8 +/- 1.5 microM, Vmax = 2.1 +/- 0.5 nmol min-1 g-1, n = 4) by perfusing hearts with varying concentrations of L-noradrenaline (1-10 microM). Various known inhibitors of noradrenaline uptake were investigated to determine whether uptake was mediated by neuronal (uptake1) and/or extraneuronal (uptake2) mechanisms. Desipramine (5 microM), imipramine (5 microM) and metaraminol (2 microM) resulted in a 66-94% inhibition of noradrenaline influx. In comparison, the steroids, 17 beta-oestradiol (1 microM) and corticosterone (10 microM), and the noradrenaline metabolite normetanephrine (5 microM) caused virtually no inhibitory effects. The beta-adrenergic antagonist propranolol (5 microM) was also relatively ineffective. These results together with the kinetic constants estimated suggest that the rapid noradrenaline uptake reflects transport into adrenergic neurones lying in the coronary interstitium. The high resolution of this paired-tracer dilution technique has permitted a 'non-invasive' study of neuronal uptake mechanisms and its application may be of clinical value. PMID:6425496

Pentachlorophenol: Uptake/elimination kinetics and metabolism in an aquatic plant, Eichhornia crassipes

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

Roy, S.; Haenninen, O.

1994-05-01

Eichhornia crassipes [(Mart) Solms], an aquatic plant widely used for the treatment of wastewaters, was used to study uptake/elimination kinetics and metabolism of pentachlorophenol (PCP). PCP is a well-known industrial by-product and a major pollutant of the aquatic environment. The initial phase of PCP uptake by the plant was rapid and reached a nearly steady state between 24 and 48 h of exposure to PCP. The major by-products of PCP metabolisms in Eichhornia crassipes were identified as ortho- and para- substituted chlorohydroxyphenols (chlorocatechols and -hydroquiones), -anisoles, and -veratroles. Partially dechlorinated products of PCP were also detected. A major portion ofmore » the absorbed PCP and metabolites was found in bound/conjugated form. The response of the enzyme systems involved in the xenobiotic metabolism and antioxidative system were also studied following PCP exposure. A significant increase was observed in the activity of glutathione S-transferase (GST), a major conjugating enzyme, and in the activities of superoxide dismutase and ascorbate peroxidase of PCP exposed plants. Such responses of plant enzymes may be implemented as useful markers of aquatic pollution. The result related to the uptake and metabolism of PCP obtained from the present study suggests a crucial role of aquatic plants in determining the fate of environmental chemicals.« less

Stabilization of metal(loid)s in two contaminated agricultural soils: Comparing biochar to its non-pyrolysed source material.

PubMed

Trakal, Lukáš; Raya-Moreno, Irene; Mitchell, Kerry; Beesley, Luke

2017-08-01

Two metal(loid) contaminated agricultural soils were amended with grape stalk (wine production by-product)-derived biochar as well as its pre-pyrolysed origin material, to investigate their geochemical impacts on As, Cr, Cu and Zn. Detailed physico-chemical evaluation combined with a column leaching test determined the retention of metal(loid)s from soil solution by each amendments. A pot experiment measured metal(loid)s in soil pore water and their uptake to ryegrass when the amendments were mixed into soils at 1 and 5% (w/w). Total Cr and Zn concentrations were reduced furthest in column leachates by the addition of raw material and biochar respectively, compared to the untreated soil; Cr(III) was the predominant specie initially due to rapid acidification of leachates and organic complexation resulting from raw material addition. Loadings of metal(loid)s to the amendments recovered from the post-leached columns were in the order Cu » Zn > Cr ≈ As. In the pot test ryegrass Cr uptake was initiated by the addition of both amendments, compared to the untreated soil, whereas only biochar addition resulted in significant increases in Zn uptake, explained by its significant enhancement of ryegrass biomass yield, especially at 5% dosage; raw material addition significantly decreased biomass yields. Inconsistent relationships between pore water parameters and ryegrass uptake were common to both soils investigated. Therefore, whilst both amendments modified soil metal(loid) geochemistry, their effects differed fundamentally; in environmental risk management terms these results highlight the need to investigate the detailed geochemical response of contaminated soils to diverse organic amendment additions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maximal Oxygen Uptake, Sweating and Tolerance to Exercise in the Heat

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Castle, B. L.; Ruff, W. K.

1972-01-01

The physiological mechanisms that facilitate acute acclimation to heat have not been fully elucidated, but the result is the establishment of a more efficient cardiovascular system to increase heat dissipation via increased sweating that allows the acclimated man to function with a cooler internal environment and to extend his performance. Men in good physical condition with high maximal oxygen uptakes generally acclimate to heat more rapidly and retain it longer than men in poorer condition. Also, upon first exposure trained men tolerate exercise in the heat better than untrained men. Both resting in heat and physical training in a cool environment confer only partial acclimation when first exposed to work in the heat. These observations suggest separate additive stimuli of metabolic heat from exercise and environmental heat to increase sweating during the acclimation process. However, the necessity of utilizing physical exercise during acclimation has been questioned. Bradbury et al. (1964) have concluded exercise has no effect on the course of heat acclimation since increased sweating can be induced by merely heating resting subjects. Preliminary evidence suggests there is a direct relationship between the maximal oxygen uptake and the capacity to maintain thermal regulation, particularly through the control of sweating. Since increased sweating is an important mechanism for the development of heat acclimation, and fit men have high sweat rates, it follows that upon initial exposure to exercise in the heat, men with high maximal oxygen uptakes should exhibit less strain than men with lower maximal oxygen uptakes. The purpose of this study was: (1) to determine if men with higher maximal oxygen uptakes exhibit greater tolerance than men with lower oxygen uptakes during early exposure to exercise in the heat, and (2) to investigate further the mechanism of the relationship between sweating and maximal work capacity.

The foliar uptake and downward translocation of trichloroethylene and 1,2,3-trichlorobenzene in air-plant-water systems.

PubMed

Su, Yuhong; Liang, Yongchao

2013-05-15

The foliar uptake and downward translocation of trichloroethylene (TCE) and 1,2,3-trichlorobenzene (TCB) in wheat, corn, and tomato seedlings were investigated following 2-48-h exposure of the plant shoots to vapor-contaminated air. The results showed that both TCE and TCB could be rapidly transported from air to plant rhizosphere solution through the foliar uptake and downward transport; the TCE and TCB concentrations in rhizosphere solutions increased with exposure time and external contaminant concentration. Among the three plant species studied, the TCE and TCB downward transport followed the order of wheat>tomato>corn. The transport efficiency of TCE by the three plants was far greater than that of TCB. With a 24-h uptake time, the amounts of TCE transported into the rhizosphere solution by wheat, tomato, and corn seedlings were 2.39 ± 0.42, 1.50 ± 0.22 and 1.45 ± 0.08 μg TCE per gram of fresh weight biomass, respectively, when the initial external TCE concentration was set at 12 mg l(-1). In a 48-h uptake experiment with corn seedlings, the TCE concentration in the rhizosphere solutions was lower in the TCE-TCB mixture system than in the single TCE system, whereas there was no significant difference in TCB concentration between the single TCB and TCE-TCB mixture systems at 48 h. The downward transport processes of TCE were inhibited, while those of TCB were enhanced in the mixed contaminant system within a 48-h uptake time. Copyright © 2013 Elsevier B.V. All rights reserved.

Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

PubMed

Nottage, Kerri A; Ware, Russell E; Winter, Bryan; Smeltzer, Matthew; Wang, Winfred C; Hankins, Jane S; Dertinger, Stephen D; Shulkin, Barry; Aygun, Banu

2014-11-01

More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function. Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc(99) m liver-spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, <10% uptake, decreased but ≥10% uptake, and normal. Mean age (N = 40) was 9.1 yrs, range 2.3-17.0. After 3 yrs of treatment, 13 (33%) had uptake on LS scan. These 13 children were younger (median age 6.0 vs. 10.6 yrs, P = 0.008), had a higher HbF at baseline (mean 10.2% vs. 5.8%, P = 0.004) and after 3 yrs (22.9% vs. 13.9%, P < 0.001), achieved MTD more rapidly (median 288 vs. 358 d, P = 0.021), and were more likely to have baseline splenic uptake (P < 0.001). Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability.

PubMed

Stiles, Mitchell F; Campbell, Leanne R; Graff, Donald W; Jones, Bobbette A; Fant, Reginald V; Henningfield, Jack E

2017-09-01

Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability. The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers. Enrolled subjects' ratings of subjective effects and nicotine uptake over 6 h were used to measure abuse liability and pharmacokinetics following in-clinic use of each EC. Use of Vuse Solo resulted in subjective measures and nicotine uptake that were between those of combustible cigarettes and nicotine gum, although generally closer to nicotine gum. Compared to combustible cigarettes, use of Vuse Solo resulted in significantly lower scores in measures of product liking, positive effects, and intent to use again. These pharmacodynamic findings were consistent with the pharmacokinetic data, showing that cigarettes produced substantially faster and higher levels of nicotine uptake as compared to Vuse Solo and nicotine gum. Vuse Solo resulted in more rapid initial uptake of nicotine compared to nicotine gum, but peak concentration and long-term extent of uptake were not different or were lower with Vuse. Collectively, these findings suggest that Vuse Solo likely has an abuse liability that is somewhat greater than nicotine gum but lower than cigarettes. ClinicalTrials.gov identifier: NCT02269514.

Evidence for rapid uptake of D-galacturonic acid in the yeast Saccharomyces cerevisiae by a channel-type transport system.

PubMed

Souffriau, Ben; den Abt, Tom; Thevelein, Johan M

2012-07-30

D-Galacturonic acid is a major component of pectins but cannot be metabolized by Saccharomyces cerevisiae. It is assumed not to be taken up. We show that yeast displays surprisingly rapid low-affinity uptake of D-galacturonic acid, strongly increasing with decreasing extracellular pH and without saturation up to 1.5 M. There was no intracellular concentration above the extracellular level and transport was reversible. Among more than 160 single and multiple deletion mutants in channels and transporters, no strain was affected in D-galacturonic acid uptake. The uptake was not inhibited by any compound tested as candidate competitive inhibitor, including D-glucuronic acid, which was also transported. The characteristics of D-galacturonic acid uptake are consistent with involvement of a channel-type system, probably encoded by multiple genes. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Immobilization rapidly induces thioredoxin-interacting protein (TXNIP) gene expression together with insulin resistance in rat skeletal muscle.

PubMed

Kawamoto, Emi; Tamakoshi, Keigo; Ra, Song-Gyu; Masuda, Hiroyuki; Kawanaka, Kentaro

2018-05-24

Acute short-duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Since thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-hr hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral non-immobilized hindlimbs were excised and examined. The 6-hr immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats sacrificed 6 hr after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions (pretreatment with transcription inhibitor actinomycin D or AMPK activator AICAR) also suppressed the increase in TXNIP protein expression in 6-hr-immobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue.

Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

PubMed

Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

2014-06-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells

PubMed Central

Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.

2014-01-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine. PMID:24706984

Architecture and Initial Development of a Knowledge-as-a-Service Activator for Computable Knowledge Objects for Health.

PubMed

Flynn, Allen J; Boisvert, Peter; Gittlen, Nate; Gross, Colin; Iott, Brad; Lagoze, Carl; Meng, George; Friedman, Charles P

2018-01-01

The Knowledge Grid (KGrid) is a research and development program toward infrastructure capable of greatly decreasing latency between the publication of new biomedical knowledge and its widespread uptake into practice. KGrid comprises digital knowledge objects, an online Library to store them, and an Activator that uses them to provide Knowledge-as-a-Service (KaaS). KGrid's Activator enables computable biomedical knowledge, held in knowledge objects, to be rapidly deployed at Internet-scale in cloud computing environments for improved health. Here we present the Activator, its system architecture and primary functions.

Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles.

PubMed

Dufes, Christine; Muller, Jean-Marc; Couet, William; Olivier, Jean-Christophe; Uchegbu, Ijeoma F; Schätzlein, Andreas G

2004-01-01

The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug.

Subunit III-depleted cytochrome c oxidase provides insight into the process of proton uptake by proteins

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan P.

2011-01-01

We review studies of subunit III-depleted cytochrome c oxidase (CcO III (−)) that elucidate the structural basis of steady-state proton uptake from solvent into an internal proton transfer pathway. The removal of subunit III from R. sphaeroides CcO makes proton uptake into the D pathway a rate-determining step, such that measurements of the pH dependence of steady-state O2 consumption can be used to compare the rate and functional pKa of proton uptake by D pathways containing different initial proton acceptors. The removal of subunit III also promotes spontaneous suicide inactivation by CcO, greatly shortening its catalytic lifespan. Because the probability of suicide inactivation is controlled by the rate at which the D pathway delivers protons to the active site, measurements of catalytic lifespan provide a second method to compare the relative efficacy of proton uptake by engineered CcO III (−) forms. These simple experimental systems have been used to explore general questions of proton uptake by proteins, such as the functional value of an initial proton acceptor, whether an initial acceptor must be surface-exposed, which side chains will function as initial proton acceptors and whether multiple acceptors can speed proton uptake. PMID:22023935

A Radiochemical Biotechnological Approach: Preliminary Study of Lactose Uptake Rate by Kefir Cells, Using 14C-labeled Lactose, in Anaerobic Fermentation

NASA Astrophysics Data System (ADS)

Golfinopoulos, A.; Soupioni, M.; Kanellaki, M.; Koutinas, A. A.

2008-08-01

The effect of initial lactose concentration on lactose uptake rate by kefir free cells, during the lactose fermentation, was studied in this work. For the investigation 14C-labelled lactose was used due to the fact that labeled and unlabeled molecules are fermented in the same way. The results illustrated lactose uptake rates are about up to two fold higher at lower initial ∘Bé densities as compared with higher initial ∘Bé densities.

Vacuolar biogenesis and aquaporin expression at early germination of broad bean seeds.

PubMed

Novikova, Galina V; Tournaire-Roux, Colette; Sinkevich, Irina A; Lityagina, Snejana V; Maurel, Christophe; Obroucheva, Natalie

2014-09-01

A key event in seed germination is water uptake-mediated growth initiation in embryonic axes. Vicia faba var. minor (broad bean) seeds were used for studying cell growth, vacuolar biogenesis, expression and function of tonoplast water channel proteins (aquaporins) in embryonic axes during seed imbibition, radicle emergence and growth. Hypocotyl and radicle basal cells showed vacuole restoration from protein storage vacuoles, whereas de novo vacuole formation from provacuoles was observed in cells newly produced by root meristem. cDNA fragments of seven novel aquaporin isoforms including five Tonoplast Intrinsic Proteins (TIP) from three sub-types were amplified by PCR. The expression was probed using q-RT-PCR and when possible with isoform-specific antibodies. Decreased expression of TIP3s was associated to the transformation of protein storage vacuoles to vacuoles, whereas enhanced expression of a TIP2 homologue was closely linked to the fast cell elongation. Water channel functioning checked by inhibitory test with mercuric chloride showed closed water channels prior to growth initiation and active water transport into elongating cells. The data point to a crucial role of tonoplast aquaporins during germination, especially during growth of embryonic axes, due to accelerated water uptake and vacuole enlargement resulting in rapid cell elongation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Metal ion removal from aqueous solution using physic seed hull.

PubMed

Mohammad, Masita; Maitra, Saikat; Ahmad, Naveed; Bustam, Azmi; Sen, T K; Dutta, Binay K

2010-07-15

The potential of physic seed hull (PSH), Jantropha curcas L. as an adsorbent for the removal of Cd(2+) and Zn(2+) metal ions from aqueous solution has been investigated. It has been found that the amount of adsorption for both Cd(2+) and Zn(2+) increased with the increase in initial metal ions concentration, contact time, temperature, adsorbent dosage and the solution pH (in acidic range), but decreased with the increase in the particle size of the adsorbent. The adsorption process for both metal ions on PSH consists of three stages-a rapid initial adsorption followed by a period of slower uptake of metal ions and virtually no uptake at the final stage. The kinetics of metal ions adsorption on PSH followed a pseudo-second-order model. The adsorption equilibrium data were fitted in the three adsorption isotherms-Freundlich, Langmuir and Dubinin-Radushkevich isotherms. The data best fit in the Langmuir isotherm indication monolayer chemisorption of the metal ions. The adsorption capacity of PSH for both Zn(2+) and Cd(2+) was found to be comparable with other available adsorbents. About 36-47% of the adsorbed metal could be leached out of the loaded PSH using 0.1M HCl as the eluting medium. 2010 Elsevier B.V. All rights reserved.

Mechanism of uptake of nitrosoureas by L5178Y lymphoblasts in vitro.

PubMed

Begleiter, A; Lam, H P; Goldenberg, G J

1977-04-01

The mechanism of uptake of nitrosoureas by L5178Y cells in vitro was investigated. A time course of the uptake of radioactivity on incubation of L5178Y lymphoblast with [14C]-1,3-bis(2-chloroethyl)-1-nitrosourea was linear for 30 min and then entered a plateau phase; it was markedly temperature dependent. A similar time course for cells incubated with [14C]ethylene-labeled 1-(2-chlorethyl)-3-cyclohexyl-1-nitrosourea reached equilibrium rapidly, was temperature independent, and resulted in a relatively low level of uptake of radioactivity. However, cells treated with 3-[cyclohexyl-14C]-1-(2-chlorethyl)-1-nitrosourea had a time course that was linear for 30 min, resulted in much higher levels of uptake of radioactivity, and was strongly temperature dependent. These findings, at least for 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, suggest that some drug decomposition precedes uptake. The percentage of radioactivity found in the cell sap fraction was at least 85% of total cell activity when cells were incubated with any of the three 14C-labeled nitrosoureas. Furthermore, thin-layer chromatography of the cell sap fraction revealed the presence of free intact drug. These findings indicate that intracellular uptake of intact nitrosoureas occurred. A time course of uptake of intact 1,3-bis(2-chloroethyl)-1-nitrosourea reached equilibrium rapidly with cell/medium distribution ratios of 0.2 to 0.6 and was temperature independent. The addition of excess unlabeled 1,3-bis(2-chlorethyl)-1-nitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea had no effect on uptake of [14C]-1,3-bis(2-chloroethyl)-1-nitrosourea, These findings suggest that uptake of intact 1,3-bis(2-chloroethyl)-1-nitrosourea was by passive diffusion. A time course of the uptake of intact 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea with either [14C]ethylene- or ring-labeled drug rapidly reached equilibrium, was temperature independent, and attained a cell/medium ratio greater than unity. Uptake of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was sodium independent and was unaffected by the metabolic inhibitors (sodium fluoride, sodium cyanide, or 2,4-dinitrophenol) or by urea, a potential physiological competitor. Furthermore, addition of unlabeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea or 1,3-bis(2-chlorethyl)-1-nitrosourea had no effect on uptake of labeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. These findings suggest that uptake of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea also occurs by passive diffusion.

Differential uptake of recent Papanicolaou testing by HPV vaccination status among young women in the United States, 2008-2013.

PubMed

Sauer, Ann Goding; Jemal, Ahmedin; Simard, Edgar P; Fedewa, Stacey A

2015-08-01

A positive association between recent Papanicolaou (Pap) test uptake and initiation of HPV vaccination among U.S. women has been reported. However, it is unknown whether recent Pap testing by HPV vaccination status varies by race/ethnicity. Discerning racial/ethnic variations is important given the higher prevalence of HPV types other than 16 and 18 in some racial/ethnic groups. We assessed whether uptake of recent Pap testing differed among women aged 21-30 years who had not initiated the HPV vaccination series versus those who had and whether this pattern differed by sociodemographic factors. 2008, 2010, and 2013 National Health Interview Survey data were used to generate weighted prevalence estimates and 95% confidence intervals (CIs) (n=7095). Adjusted predicted marginal models were used to generate adjusted prevalence ratios (aPRs) to assess the relationship between recent Pap test uptake and HPV vaccination series initiation by race/ethnicity. The uptake of recent Pap testing among those who had not initiated the HPV vaccination series was significantly lower (81.0%) compared to those who had initiated vaccination (90.5%) (aPR=0.93, 95% CI: 0.90-0.96). This finding was consistent across most sociodemographic factors, though not statistically significant for Blacks, Hispanics, those with lower levels of education, or those with higher levels of income. Young women who had not initiated HPV vaccination were less likely to have had a recent Pap test compared to women who had initiated vaccination. Concerted efforts are needed to increase uptake of recommended cervical cancer screening and HPV vaccination among young women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uptake of Workplace HIV Counselling and Testing: A Cluster-Randomised Trial in Zimbabwe

PubMed Central

Corbett, Elizabeth L; Dauya, Ethel; Matambo, Ronnie; Cheung, Yin Bun; Makamure, Beauty; Bassett, Mary T; Chandiwana, Steven; Munyati, Shungu; Mason, Peter R; Butterworth, Anthony E; Godfrey-Faussett, Peter; Hayes, Richard J

2006-01-01

Background HIV counselling and testing is a key component of both HIV care and HIV prevention, but uptake is currently low. We investigated the impact of rapid HIV testing at the workplace on uptake of voluntary counselling and testing (VCT). Methods and Findings The study was a cluster-randomised trial of two VCT strategies, with business occupational health clinics as the unit of randomisation. VCT was directly offered to all employees, followed by 2 y of open access to VCT and basic HIV care. Businesses were randomised to either on-site rapid HIV testing at their occupational clinic (11 businesses) or to vouchers for off-site VCT at a chain of free-standing centres also using rapid tests (11 businesses). Baseline anonymised HIV serology was requested from all employees. HIV prevalence was 19.8% and 18.4%, respectively, at businesses randomised to on-site and off-site VCT. In total, 1,957 of 3,950 employees at clinics randomised to on-site testing had VCT (mean uptake by site 51.1%) compared to 586 of 3,532 employees taking vouchers at clinics randomised to off-site testing (mean uptake by site 19.2%). The risk ratio for on-site VCT compared to voucher uptake was 2.8 (95% confidence interval 1.8 to 3.8) after adjustment for potential confounders. Only 125 employees (mean uptake by site 4.3%) reported using their voucher, so that the true adjusted risk ratio for on-site compared to off-site VCT may have been as high as 12.5 (95% confidence interval 8.2 to 16.8). Conclusions High-impact VCT strategies are urgently needed to maximise HIV prevention and access to care in Africa. VCT at the workplace offers the potential for high uptake when offered on-site and linked to basic HIV care. Convenience and accessibility appear to have critical roles in the acceptability of community-based VCT. PMID:16796402

Rapid Consumption of Low Concentrations of Methyl Bromide by Soil Bacteria

PubMed Central

Hines, Mark E.; Crill, Patrick M.; Varner, Ruth K.; Talbot, Robert W.; Shorter, Joanne H.; Kolb, Charles E.; Harriss, Robert C.

1998-01-01

A dynamic dilution system for producing low mixing ratios of methyl bromide (MeBr) and a sensitive analytical technique were used to study the uptake of MeBr by various soils. MeBr was removed within minutes from vials incubated with soils and ∼10 parts per billion by volume of MeBr. Killed controls did not consume MeBr, and a mixture of the broad-spectrum antibiotics chloramphenicol and tetracycline inhibited MeBr uptake by 98%, indicating that all of the uptake of MeBr was biological and by bacteria. Temperature optima for MeBr uptake suggested a biological sink, yet soil moisture and temperature optima varied for different soils, implying that MeBr consumption activity by soil bacteria is diverse. The eucaryotic antibiotic cycloheximide had no effect on MeBr uptake, indicating that soil fungi were not involved in MeBr removal. MeBr consumption did not occur anaerobically. A dynamic flowthrough vial system was used to incubate soils at MeBr mixing ratios as low as those found in the remote atmosphere (5 to 15 parts per trillion by volume [pptv]). Soils consumed MeBr at all mixing ratios tested. Temperate forest and grassy lawn soils consumed MeBr most rapidly (rate constant [k] = 0.5 min−1), yet sandy temperate, boreal, and tropical forest soils also readily consumed MeBr. Amendments of CH4 up to 5% had no effect on MeBr uptake even at CH4:MeBr ratios of 107, and depth profiles of MeBr and CH4 consumption exhibited very different vertical rate optima, suggesting that methanotrophic bacteria, like those presently in culture, do not utilize MeBr when it is at atmospheric mixing ratios. Data acquired with gas flux chambers in the field demonstrated the very rapid in situ consumption of MeBr by soils. Uptake of MeBr at mixing ratios found in the remote atmosphere occurs via aerobic bacterial activity, displays first-order kinetics at mixing ratios from 5 pptv to ∼1 part per million per volume, and is rapid enough to account for 25% of the global annual loss of atmospheric MeBr. PMID:9572964

Metabolism of pharmaceutical and personal care products by carrot cell cultures.

PubMed

Wu, Xiaoqin; Fu, Qiuguo; Gan, Jay

2016-04-01

With the increasing use of treated wastewater and biosolids in agriculture, residues of pharmaceutical and personal care products (PPCPs) in these reused resources may contaminate food produce via plant uptake, constituting a route for human exposure. Although various PPCPs have been reported to be taken up by plants in laboratories or under field conditions, at present little information is available on their metabolism in plants. In this study, we applied carrot cell cultures to investigate the plant metabolism of PPCPs. Five phase I metabolites of carbamazepine were identified and the potential metabolism pathways of carbamazepine were proposed. We also used the carrot cell cultures as a rapid screening tool to initially assess the metabolism potentials of 18 PPCPs. Eleven PPCPs, including acetaminophen, caffeine, meprobamate, primidone, atenolol, trimethoprim, DEET, carbamazepine, dilantin, diazepam, and triclocarban, were found to be recalcitrant to metabolism. The other 7 PPCPs, including triclosan, naproxen, diclofenac, ibuprofen, gemfibrozil, sulfamethoxazole, and atorvastatin, displayed rapid metabolism, with 0.4-47.3% remaining in the culture at the end of the experiment. Further investigation using glycosidase hydrolysis showed that 1.3-20.6% of initially spiked naproxen, diclofenac, ibuprofen, and gemfibrozil were transformed into glycoside conjugates. Results from this study showed that plant cell cultures may be a useful tool for initially exploring the potential metabolites of PPCPs in plants as well as for rapidly screening the metabolism potentials of a variety of PPCPs or other emerging contaminants, and therefore may be used for prioritizing compounds for further comprehensive evaluations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uptake, biotransformation, and elimination of rotenone by bluegills (Lepomis macrochirus )

USGS Publications Warehouse

Gingerich, W.H.; Rach, J.J.

1985-01-01

Yearling bluegills (Lepomis macrochirus) were exposed to sublethal concentrations of [14C]rotenone (5.2 μg/l) for 30 days in a continuous flow exposure system and then transferred to clean, flowing water for an additional 21-day depuration period. Rates of uptake and elimination and profile of the rotenoid metabolites in head, viscera, and carcass components were evaluated by 14C counting and by high performance liquid chromatography. Total [14C]rotenone derived activity was relatively uniform in all body components within 3 days after initial exposure and remained constant during the ensuing 27 days of exposure. Initial uptake rate coefficients were highest in viscera (Ku = 80· h -1) and were nearly identical for head (Ku = 14 · h) and carcass (Ku = 10 · h-1). Analyses of tissue extracts by high performance liquid chromatography confirmed the presence of at least six biotransformation products of rotenone. More than 60% of the activity extracted from viscera was present as a single peak which represented a compound that was extremely soluble in water. Rotenone composed only 0.3% of the extractable activity in viscera taken from fish exposed to rotenone for 30 days; however, rotenone accounted for 15.4% of extractable activity in the head and 20.1% in the carcass components. Rotenolone and 6',7'-dihydro-6'-,7'--dihydroxyrotenolone were tentatively identified as oxidation products in all tissue extracts. Elimination of 14C activity from all body components was biphasic; both phases followed first-order kinetics. The rate of elimination was nearly equal for all body components during the initial phase but was most rapid from viscera during the second phase of elimination. Bioconcentration factors for the head, viscera, and carcass were 165, 3,550, and 125, respectively, when calculated on the basis of total 14C activity but only 25.4, 11, and 26 when calculated as the concentration of parent material.

EVALUATION OF CHLORPYRIFOS UPTAKE IN STERILIZED AND NON-STERILIZED SEDIMENT

EPA Science Inventory

In order to evaluate chemical interactions in sediment, initial experiments were designed to assess the role of microbial activitiy on chemical fate of chlorpyrifos. In these initial experiments, sediment uptake of chlorpyrifos was evaluated using Enzyme Linked Immunosorbent Assa...

Removal and recovery of p-phenylenediamines developing compounds from photofinishing lab-washwater using clinoptilolite tuffs from Greece.

PubMed

Vlessidis, A G; Triantafillidis, C S; Evmiridis, N P

2001-04-01

Clinoptilolite tuffs from areas in Thrace region of Greece are compared with synthetic zeolites NaY and NH4Y for the uptake of N4-ethyl-N4-(2-methansulphonamidoethyl)-2-methyl-1,4-phenylenediamin (sesquisulphate, monohydrate) with the trade name CD-3 for the purpose to be used for clean-up and recycling photo-finishing and photo-developing washwaters. The cation-exchange capacity is found to be 6.15-11.1 mg/g for zeoliferous tuffs at equilibrium concentration of 50 ppm CD-3 in aqueous solution compared to 65.0 mg/g of NaY and 48.2 mg/g for NH4Y synthetic zeolites corresponding to the removal of CD-3 from 120 to 2001 of 50 ppm aqueous solution per kg of natural zeoliferous tuff; this capacity is only 6-10 times lower than type-Y synthetic zeolite. Initial rates of uptake are 20.8 mg/l/min for natural and 38.5 mg/l/min for synthetic zeolites. Regeneration levels of 55, 23, 35, and 33% are obtained for MCH, SF, NaY, and NH4Y, respectively. The rapid and almost complete uptake of CD-3 from its aqueous solutions at low CD-3 concentrations by the natural zeolites is promising for such an application.

Rapid adsorption of 2,4-dichlorophenoxyacetic acid by iron oxide nanoparticles-doped carboxylic ordered mesoporous carbon.

PubMed

Tang, Lin; Zhang, Sheng; Zeng, Guang-Ming; Zhang, Yi; Yang, Gui-De; Chen, Jun; Wang, Jing-Jing; Wang, Jia-Jia; Zhou, Yao-Yu; Deng, Yao-Cheng

2015-05-01

The ordered mesoporous carbon composite functionalized with carboxylate groups and iron oxide nanoparticles (Fe/OMC) was successfully prepared and used to adsorb 2,4-dichlorophenoxyacetic acid (2,4-D) from wastewater. The resultant adsorbent possessed high degree of order, large specific surface area and pore volume, and good magnetic properties. The increase in initial pollutant concentration and contact time would make the adsorption capacity increase, but the pH and temperature are inversely proportional to 2,4-D uptake. The equilibrium of adsorption was reached within 120 min, and the equilibrated adsorption capacity increased from 99.38 to 310.78 mg/g with the increase of initial concentration of 2,4-D from 100 to 500 mg/L. Notablely, the adsorption capacity reached 97% of the maximum within the first 5 min. The kinetics and isotherm study showed that the pseudo-second-order kinetic and Langmuir isotherm models could well fit the adsorption data. These results indicate that Fe/OMC has a good potential for the rapid adsorption of 2,4-D and prevention of its further diffusion. Copyright © 2014 Elsevier Inc. All rights reserved.

Community nurse-led initiation of antiviral therapy for chronic hepatitis C in people who inject drugs does not increase uptake of or adherence to treatment.

PubMed

Lewis, Heather; Kunkel, Jan; Axten, David; Dalton, Jane; Gardner, Hayley; Tippett, Andrew; Wynne, Stephanie; Wilkinson, Mandie; Foster, Graham R

2016-11-01

Chronic hepatitis C is common in people who inject drugs (PWID) and this population serves as a reservoir for infection. Treatment levels are low among this group, ranging from 1 to 19%. We explored whether a nurse-initiated community treatment model increased uptake of and adherence to interferon-based therapies. This was a cluster randomized trial of nurse-initiated versus physician-initiated antiviral therapy with pegylated interferon and ribavirin for hepatitis C virus in community clinics (trial registration: ISRCTN07774040). The proportion of participants initiating treatment during follow-up was 10% with nurse-initiated (6/62) and 9% with physician-initiated (6/76) therapy. Adherence was similar in both groups, with only one patient in each arm not adhering to therapy. There were no serious adverse events, but interferon-related side effects were common. Drug and alcohol use did not change during therapy. Despite easy access to antiviral therapy, uptake of treatment was poor, with no significant difference between the groups. Nurse-led initiation of interferon-based antiviral therapy in PWID did not lead to increased uptake of, response to or adherence with treatment. Further service improvement is unlikely to increase the proportion of PWID undergoing antiviral therapy for hepatitis C virus and early adoption of interferon-free regimens may increase the proportion initiating and completing treatment.

From passive tool holders to microsurgeons: safer, smaller, smarter surgical robots.

PubMed

Bergeles, Christos; Yang, Guang-Zhong

2014-05-01

Within only a few decades from its initial introduction, the field of surgical robotics has evolved into a dynamic and rapidly growing research area with increasing clinical uptake worldwide. Initially introduced for stereotaxic neurosurgery, surgical robots are now involved in an increasing number of procedures, demonstrating their practical clinical potential while propelling further advances in surgical innovations. Emerging platforms are also able to perform complex interventions through only a single-entry incision, and navigate through natural anatomical pathways in a tethered or wireless fashion. New devices facilitate superhuman dexterity and enable the performance of surgical steps that are otherwise impossible. They also allow seamless integration of microimaging techniques at the cellular level, significantly expanding the capabilities of surgeons. This paper provides an overview of the significant achievements in surgical robotics and identifies the current trends and future research directions of the field in making surgical robots safer, smaller, and smarter.

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

Guha, A.; Prasad, G.C.; Udupa, K.N.

Scintillography and autoradiography were used to study the healing of humeral fractures in rats injected with Sr/sup 85/. Among various agents studied for an influence on the rate of fracture healing, the total extract of the herb Cissus quadrangularis was tested. In both controls and animals receiving C. quadrangularis extract there was demineralization of the fractured bone at the site of fracture. In the treated group, there was a somewhat earlier rise in Sr/ sup 85/ uptake just after the first injection. Thereafter, uptake again became high, similar to the control samples from the 6th day onward. The maximum uptakemore » of control bone was found to be around the 19th day after fracturing, while in the treated group, maximum uptake was on 15th day. Though there was a minor difference in the period of maximum uptake between treated and control bone, the rate of uptake in the treated sample was markedly higher than that of the control sample. The fall of Sr/sup 85/ uptake in the treated bone was very rapid, whereas in the untreated animals it was more gradual. All these findings on the uptake of Sr/sup 85/ as measured by a G-M counter, corroborated x-ray pictures and gross autoradiography at different stages of fracture healing. The radiological and autoradiographic findings also clearly showed that the healing in the treated group was quicker than in the controls. Furthermore, the callus in the treated animals underwent remodeling processes much earlier than in the nontreated ones. It is concluded that if the uptake of Sr in the treated andimals is greater thand in the control samples at the site of fracture, healing activity is more pronounced. However, studies on patients have shown that the uptake of Sr/sup 85/ alone in the fractured region may not give an accurate picture of the healing processes. Thus, at the end of first week after fractures, accretion rate of Ca reached a peak and thereafter remained higher than normal throughout the period of healing. But when these results were compared with x-ray pictures, it was observed that the accretion rate in poorly uniting fractures did not diifer from that of normally healing fractures, so that in interpreting the rate of healing by the uptake of Sr/sup 85/, radiography is also required to make the correct assessment of the status of fracture healing. The Sr/sup 85/ uptake curves show that the uptake pattern can be divided into three definite phases. ln the first phase, which lasts for six days, there is and enormous amount of decalcification from the broken fragments of bone possibly due to increased vascularity of the region, and also to the increased accumulation of mucopolysaccharides locally. In the second phase, which lasts for another 8 to 12 days, rapid increase in the accretion of Ca as evidenced by increase in the uptake of Sr/sup 85/ noted. During the 2nd phase, histologic studies indicated that large amounts of collagen fibers appear, which possibly combine with all the available Ca salts there. The third phase shows a rapid fall of Sr/sup 85/ uptake, indicating that the callus formed in the second phase is rapidly being remodeled. (BBB)« less

Rapid Recycling of Ca2+ between IP3-Sensitive Stores and Lysosomes

PubMed Central

López Sanjurjo, Cristina I.; Tovey, Stephen C.; Taylor, Colin W.

2014-01-01

Inositol 1,4,5-trisphosphate (IP3) evokes release of Ca2+ from the endoplasmic reticulum (ER), but the resulting Ca2+ signals are shaped by interactions with additional intracellular organelles. Bafilomycin A1, which prevents lysosomal Ca2+ uptake by inhibiting H+ pumping into lysosomes, increased the amplitude of the initial Ca2+ signals evoked by carbachol in human embryonic kidney (HEK) cells. Carbachol alone and carbachol in combination with parathyroid hormone (PTH) evoke Ca2+ release from distinct IP3-sensitive Ca2+ stores in HEK cells stably expressing human type 1 PTH receptors. Bafilomycin A1 similarly exaggerated the Ca2+ signals evoked by carbachol or carbachol with PTH, indicating that Ca2+ released from distinct IP3-sensitive Ca2+ stores is sequestered by lysosomes. The Ca2+ signals resulting from store-operated Ca2+ entry, whether evoked by thapsigargin or carbachol, were unaffected by bafilomycin A1. Using Gd3+ (1 mM) to inhibit both Ca2+ entry and Ca2+ extrusion, HEK cells were repetitively stimulated with carbachol to assess the effectiveness of Ca2+ recycling to the ER after IP3-evoked Ca2+ release. Blocking lysosomal Ca2+ uptake with bafilomycin A1 increased the amplitude of each carbachol-evoked Ca2+ signal without affecting the rate of Ca2+ recycling to the ER. This suggests that Ca2+ accumulated by lysosomes is rapidly returned to the ER. We conclude that lysosomes rapidly, reversibly and selectively accumulate the Ca2+ released by IP3 receptors residing within distinct Ca2+ stores, but not the Ca2+ entering cells via receptor-regulated, store-operated Ca2+ entry pathways. PMID:25337829

Rapid recycling of Ca2+ between IP3-sensitive stores and lysosomes.

PubMed

López Sanjurjo, Cristina I; Tovey, Stephen C; Taylor, Colin W

2014-01-01

Inositol 1,4,5-trisphosphate (IP3) evokes release of Ca2+ from the endoplasmic reticulum (ER), but the resulting Ca2+ signals are shaped by interactions with additional intracellular organelles. Bafilomycin A1, which prevents lysosomal Ca2+ uptake by inhibiting H+ pumping into lysosomes, increased the amplitude of the initial Ca2+ signals evoked by carbachol in human embryonic kidney (HEK) cells. Carbachol alone and carbachol in combination with parathyroid hormone (PTH) evoke Ca2+ release from distinct IP3-sensitive Ca2+ stores in HEK cells stably expressing human type 1 PTH receptors. Bafilomycin A1 similarly exaggerated the Ca2+ signals evoked by carbachol or carbachol with PTH, indicating that Ca2+ released from distinct IP3-sensitive Ca2+ stores is sequestered by lysosomes. The Ca2+ signals resulting from store-operated Ca2+ entry, whether evoked by thapsigargin or carbachol, were unaffected by bafilomycin A1. Using Gd3+ (1 mM) to inhibit both Ca2+ entry and Ca2+ extrusion, HEK cells were repetitively stimulated with carbachol to assess the effectiveness of Ca2+ recycling to the ER after IP3-evoked Ca2+ release. Blocking lysosomal Ca2+ uptake with bafilomycin A1 increased the amplitude of each carbachol-evoked Ca2+ signal without affecting the rate of Ca2+ recycling to the ER. This suggests that Ca2+ accumulated by lysosomes is rapidly returned to the ER. We conclude that lysosomes rapidly, reversibly and selectively accumulate the Ca2+ released by IP3 receptors residing within distinct Ca2+ stores, but not the Ca2+ entering cells via receptor-regulated, store-operated Ca2+ entry pathways.

Rapid adaptation of activated sludge bacteria into a glycogen accumulating biofilm enabling anaerobic BOD uptake.

PubMed

Hossain, Md Iqbal; Paparini, Andrea; Cord-Ruwisch, Ralf

2017-03-01

Glycogen accumulating organisms (GAO) are known to allow anaerobic uptake of biological oxygen demand (BOD) in activated sludge wastewater treatment systems. In this study, we report a rapid transition of suspended activated sludge biomass to a GAO dominated biofilm by selective enrichment using sequences of anaerobic loading followed by aerobic exposure of the biofilm to air. The study showed that within eight weeks, a fully operational, GAO dominated biofilm had developed, enabling complete anaerobic BOD uptake at a rate of 256mg/L/h. The oxygen uptake by the biofilm directly from the atmosphere had been calculated to provide significant energy savings. This study suggests that wastewater treatment plant operators can convert activated sludge systems readily into a "passive aeration" biofilm that avoids costly oxygen transfer to bulk wastewater solution. The described energy efficient BOD removal system provides an opportunity to be coupled with novel nitrogen removal processes such as anammox. Copyright © 2016. Published by Elsevier Ltd.

Renewable Electricity Use by the U.S. Information and Communication Technology (ICT) Industry

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

Miller, John; Bird, Lori; Heeter, Jenny

The information and communication technology (ICT) sector continues to witness rapid growth and uptake of ICT equipment and services at both the national and global levels. The electricity consumption associated with this expansion is substantial, although recent adoptions of cloudcomputing services, co-location data centers, and other less energy-intensive equipment and operations have likely reduced the rate of growth in this sector. This paper is intended to aggregate existing ICT industry data and research to provide an initial look at electricity use, current and future renewable electricity acquisition, as well as serve as a benchmark for future growth and trends inmore » ICT industry renewable electricity consumption.« less

Energy independent uptake and release of polystyrene nanoparticles in primary mammalian cell cultures.

PubMed

Fiorentino, Ilaria; Gualtieri, Roberto; Barbato, Vincenza; Mollo, Valentina; Braun, Sabrina; Angrisani, Alberto; Turano, Mimmo; Furia, Maria; Netti, Paolo A; Guarnieri, Daniela; Fusco, Sabato; Talevi, Riccardo

2015-01-15

Nanoparticle (NPs) delivery systems in vivo promises to overcome many obstacles associated with the administration of drugs, vaccines, plasmid DNA and RNA materials, making the study of their cellular uptake a central issue in nanomedicine. The uptake of NPs may be influenced by the cell culture stage and the NPs physical-chemical properties. So far, controversial data on NPs uptake have been derived owing to the heterogeneity of NPs and the general use of immortalized cancer cell lines that often behave differently from each other and from primary mammalian cell cultures. Main aims of the present study were to investigate the uptake, endocytosis pathways, intracellular fate and release of well standardized model particles, i.e. fluorescent 44 nm polystyrene NPs (PS-NPs), on two primary mammalian cell cultures, i.e. bovine oviductal epithelial cells (BOEC) and human colon fibroblasts (HCF) by confocal microscopy and spectrofluorimetric analysis. Different drugs and conditions that inhibit specific internalization routes were used to understand the mechanisms that mediate PS-NP uptake. Our data showed that PS-NPs are rapidly internalized by both cell types 1) with similar saturation kinetics; 2) through ATP-independent processes, and 3) quickly released in the culture medium. Our results suggest that PS-NPs are able to rapidly cross the cell membrane through passive translocation during both uptake and release, and emphasize the need to carefully design NPs for drug delivery, to ensure their selective uptake and to optimize their retainment in the targeted cells. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Golfinopoulos, A.; Soupioni, M.; Kanellaki, M.

The effect of initial lactose concentration on lactose uptake rate by kefir free cells, during the lactose fermentation, was studied in this work. For the investigation {sup 14}C-labelled lactose was used due to the fact that labeled and unlabeled molecules are fermented in the same way. The results illustrated lactose uptake rates are about up to two fold higher at lower initial (convolution sign)Be densities as compared with higher initial (convolution sign)Be densities.

Maple sap uptake, exudation, and pressure changes correlated with freezing exotherms and thawing endotherms.

PubMed

Tyree, M T

1983-10-01

Sap flow rates and sap pressure changes were measured in dormant sugar maple trees (Acer saccharum Marsh.). In the forest, sap flow rates and pressure changes were measured from tap holes drilled into tree trunks in mature trees and sap flow rates were measured from the base of excised branches. Excised branches were also brought into the laboratory where air temperature could be carefully controlled in a refrigerated box and sap flow rates and sap pressures were measured from the cut base of the branches.Under both forest and laboratory conditions, sap uptake occurred as the wood temperature declined but much more rapid sap uptake correlated with the onset of the freezing exotherm. When sap pressures were measured under conditions of negligible volume displacement, the sap pressure rapidly fell to -60 to -80 kilopascals at the start of the freezing exotherm. The volume of water uptake and the rate of uptake depended on the rate of freezing. A slow freezing rate correlated with a large volume of water uptake, a fast freezing rate induced a smaller volume of water uptake. The volume of water uptake ranged from 0.02 to 0.055 grams water per gram dry weight of sapwood. The volume of water exuded after thawing was usually less than the volume of uptake so that after several freezing and thawing cycles the sapwood water content increased from 0.7 to 0.8 grams water per gram dry weight.These results are discussed in terms of a physical model of the mechanism of maple sap uptake and exudation first proposed by P. E. R. O'Malley. The proposed mechanism of sap uptake is by vapor distillation in air filled wood fiber lumina during the freezing of minor branches. Gravity and pressurized air bubbles (compressed during freezing) cause sap flow from the canopy down the tree after the thaw.

Maple Sap Uptake, Exudation, and Pressure Changes Correlated with Freezing Exotherms and Thawing Endotherms 1

PubMed Central

Tyree, Melvin T.

1983-01-01

Sap flow rates and sap pressure changes were measured in dormant sugar maple trees (Acer saccharum Marsh.). In the forest, sap flow rates and pressure changes were measured from tap holes drilled into tree trunks in mature trees and sap flow rates were measured from the base of excised branches. Excised branches were also brought into the laboratory where air temperature could be carefully controlled in a refrigerated box and sap flow rates and sap pressures were measured from the cut base of the branches. Under both forest and laboratory conditions, sap uptake occurred as the wood temperature declined but much more rapid sap uptake correlated with the onset of the freezing exotherm. When sap pressures were measured under conditions of negligible volume displacement, the sap pressure rapidly fell to −60 to −80 kilopascals at the start of the freezing exotherm. The volume of water uptake and the rate of uptake depended on the rate of freezing. A slow freezing rate correlated with a large volume of water uptake, a fast freezing rate induced a smaller volume of water uptake. The volume of water uptake ranged from 0.02 to 0.055 grams water per gram dry weight of sapwood. The volume of water exuded after thawing was usually less than the volume of uptake so that after several freezing and thawing cycles the sapwood water content increased from 0.7 to 0.8 grams water per gram dry weight. These results are discussed in terms of a physical model of the mechanism of maple sap uptake and exudation first proposed by P. E. R. O'Malley. The proposed mechanism of sap uptake is by vapor distillation in air filled wood fiber lumina during the freezing of minor branches. Gravity and pressurized air bubbles (compressed during freezing) cause sap flow from the canopy down the tree after the thaw. PMID:16663208

Aridity and plant uptake interact to make dryland soils hotspots for nitric oxide (NO) emissions

PubMed Central

Blankinship, Joseph C.; Marchus, Kenneth; Lucero, Delores M.; Sickman, James O.; Schimel, Joshua P.

2016-01-01

Nitric oxide (NO) is an important trace gas and regulator of atmospheric photochemistry. Theory suggests moist soils optimize NO emissions, whereas wet or dry soils constrain them. In drylands, however, NO emissions can be greatest in dry soils and when dry soils are rewet. To understand how aridity and vegetation interact to generate this pattern, we measured NO fluxes in a California grassland, where we manipulated vegetation cover and the length of the dry season and measured [δ15-N]NO and [δ18-O]NO following rewetting with 15N-labeled substrates. Plant N uptake reduced NO emissions by limiting N availability. In the absence of plants, soil N pools increased and NO emissions more than doubled. In dry soils, NO-producing substrates concentrated in hydrologically disconnected microsites. Upon rewetting, these concentrated N pools underwent rapid abiotic reaction, producing large NO pulses. Biological processes did not substantially contribute to the initial NO pulse but governed NO emissions within 24 h postwetting. Plants acted as an N sink, limiting NO emissions under optimal soil moisture. When soils were dry, however, the shutdown in plant N uptake, along with the activation of chemical mechanisms and the resuscitation of soil microbial processes upon rewetting, governed N loss. Aridity and vegetation interact to maintain a leaky N cycle during periods when plant N uptake is low, and hydrologically disconnected soils favor both microbial and abiotic NO-producing mechanisms. Under increasing rates of atmospheric N deposition and intensifying droughts, NO gas evasion may become an increasingly important pathway for ecosystem N loss in drylands. PMID:27114523

Exchange of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) between air and a mixed pasture sward.

PubMed

Barber, Jonathan L; Thomas, Gareth O; Bailey, Rebekah; Kerstiens, Gerhard; Jones, Kevin C

2004-07-15

To improve understanding of air-to-vegetation transfer of persistent organic pollutants (POPs), uptake and depuration of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) between grass sward and air was investigated. Pasture swards were placed in fanned (2 m s(-1) wind speed) and unfanned conditions for a period of 20 days and sampled at intervals. Depuration was carried out after a short (4 days) and a long (14 days) exposure period. Prior to contamination, a mixed pasture sward at a semi-rural location contained sigmaPCN concentrations 15-20% of the sigmaPCB concentration. Uptake of both PCBs and PCNs was broadly linear in fanned and unfanned conditions over the 20-day period, i.e., the pasture did not reach equilibrium with the air. Uptake rates (fluxes) were greater under the fanned conditions. The difference in uptake rates between fanned and unfanned conditions increased with degree of chlorination for both PCBs and PCNs, ranging between a factor of 2 for tri-chlorinated PCBs and PCNs and a factor 5 for octa-chlorinated PCBs. Depuration results over the first hours were very scattered, showing an initial period of loss, followed by an increase in concentrations, possibly as a result of re-volatilization of PCBs from the soil in the trays, with consequent recapture by the overlying sward. Rapid clearance was observed over the following days, but depuration of PCBs and PCNs was still incomplete after 14 days, with 20% of the initial concentration of the sigmaPCBs and 10% of the sigmaPCNs retained by the sward. There was no difference in the proportion of POPs retained in the sward between the 4- and 14-day contamination treatments. POP-specific differences in the amount of compound "trapped" in leaves after contamination were observed. The results show that, although changes in the rate of air movement around a pasture have an effect on the uptake rate of POPs into the vegetation, plant-side resistance controls both the air-to-pasture and pasture-to-air exchange of gas-phase PCBs and PCNs; i.e., differences between plant species in cuticle composition and/or structure affecting the permeability of the cuticle are of greater importance than differences in leaf morphology affecting aerodynamic roughness.

[C-11]{beta}CNT: A new monoamine uptake ligand for studying serotonin and dopamine transporter sites in the living brain with PET

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

Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C.

1996-05-01

There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically puremore » {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.« less

Monosaccharide transport into hemocytes of a sipunculan worm Themiste dyscrita

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

Ingermann, R.L.; Hall, R.E.; Bissonnette, J.M.

1985-07-01

The hemerythrin-containing blood cells, or hemocytes, of the sipunculan worm Themiste dyscrita were found to have a stereospecific and nonconcentrative monosaccharide transport system. The transport system transferred both D-glucose and 3-O-methyl-D-glucose (3-OMG), and transport into cells by this system was rapid, reaching 50% equilibrium in approximately 20 s at 10 degrees C with an initial concentration gradient of 0.1 mM; the contribution to total uptake by simple diffusion was very small. 3-OMG uptake showed saturation kinetics with a low half-saturation constant (Km less than or equal to 0.1 mM). The uptake of labeled 3-OMG by the hemocytes was strongly inhibitedmore » by unlabeled 3-OMG, 2-deoxy-D-glucose, alpha- and beta-D-glucose, D-galactose, and D-mannose. It was moderately inhibited by D-xylose, only slightly by alpha-methyl-D-glucoside and D-fructose, and uninhibited by sucrose, L-glucose, or D-sorbitol. Phloretin was more potent than phloridzin in blocking entry of 3-OMG. Cytochalasin B did not bind tightly to the T. dyscrita transporter and was not a potent inhibitor of transport; it half-maximally inhibited 3-OMG transport at 0.1 mM. Therefore, despite some differences the data suggest functional similarities in the mechanism of monosaccharide transport into blood cells of mammals and this invertebrate.« less

Stability and nuclear dynamics of the Bicoid morphogen gradient

PubMed Central

Gregor, Thomas; Wieschaus, Eric F.; McGregor, Alistair P.; Bialek, William; Tank, David W.

2008-01-01

Patterning in multicellular organisms results from spatial gradients in morphogen concentration, but the dynamics of these gradients remains largely unexplored. We characterize, through in vivo optical imaging, the development and stability of the Bicoid morphogen gradient in Drosophila embryos that express a Bicoid-eGFP fusion protein. The gradient is established rapidly (~1 hour after fertilization) with nuclear Bicoid concentration rising and falling during mitosis. Interphase levels result from a rapid equilibrium between Bicoid uptake and removal. Initial interphase concentration in nuclei in successive cycles is constant (±10%), demonstrating a form of gradient stability, but subsequently decays by approximately 30%. Both direct photobleaching measurements and indirect estimates of Bicoid-eGFP diffusion constants (D ≤ 1 μm2/s), provide a consistent picture of Bicoid transport on short (~min) time scales, but challenge traditional models of long range gradient formation. A new model is presented emphasizing the possible role of nuclear dynamics in shaping and scaling the gradient. PMID:17632061

Genetic identification of a gene involved in constitutive, high-affinity nitrate transport in higher plants.

PubMed Central

Wang, R; Crawford, N M

1996-01-01

Two mutations have been found in a gene (NRT2) of Arabidopsis thaliana that specifically impair constitutive, high-affinity nitrate uptake. These mutants were selected for resistance to 0.1 mM chlorate in the absence of nitrate. Progency from one of the backcrossed mutants showed no constitutive uptake of nitrate below 0.5 mM at pH 7.0 in liquid culture (that is, within 30 min of initial exposure to nitrate). All other uptake activities measured (high-affinity phosphate and sulfate uptake, inducible high-affinity nitrate uptake, and constitutive low-affinity nitrate uptake) were present or nearly normal in the backcrossed mutant. Electrophysiological analysis of individual root cells showed that the nrt2 mutant showed little response to 0.25 mM of nitrate, whereas NRT2 wild-type cells showed an initial depolarization followed by recovery. At 10 mM of nitrate both the mutant and wild-type cells displayed similar, strong electrical responses. These results indicate that NRT2 is a critical and perhaps necessary gene for constitutive, high-affinity nitrate uptake in Arabidopsis, but not for inducible, high-affinity nor constitutive, low-affinity nitrate uptake. Thus, these systems are genetically distinct. PMID:8799195

Rapid multislice T1 mapping of mouse myocardium: Application to quantification of manganese uptake in α-Dystrobrevin knockout mice.

PubMed

Jiang, Kai; Li, Wen; Li, Wei; Jiao, Sen; Castel, Laurie; Van Wagoner, David R; Yu, Xin

2015-11-01

The aim of this study was to develop a rapid, multislice cardiac T1 mapping method in mice and to apply the method to quantify manganese (Mn(2+)) uptake in a mouse model with altered Ca(2+) channel activity. An electrocardiography-triggered multislice saturation-recovery Look-Locker method was developed and validated both in vitro and in vivo. A two-dose study was performed to investigate the kinetics of T1 shortening, Mn(2+) relaxivity in myocardium, and the impact of Mn(2+) on cardiac function. The sensitivity of Mn(2+)-enhanced MRI in detecting subtle changes in altered Ca(2+) channel activity was evaluated in a mouse model with α-dystrobrevin knockout. Validation studies showed strong agreement between the current method and an established method. High Mn(2+) dose led to significantly accelerated T1 shortening. Heart rate decreased during Mn(2+) infusion, while ejection ratio increased slightly at the end of imaging protocol. No statistical difference in cardiac function was detected between the two dose groups. Mice with α-dystrobrevin knockout showed enhanced Mn(2+) uptake in vivo. In vitro patch-clamp study showed increased Ca(2+) channel activity. The saturation recovery method provides rapid T1 mapping in mouse hearts, which allowed sensitive detection of subtle changes in Mn(2+) uptake in α-dystrobrevin knockout mice. © 2014 Wiley Periodicals, Inc.

Ehrlichia chaffeensis Proliferation Begins with NtrY/NtrX and PutA/GlnA Upregulation and CtrA Degradation Induced by Proline and Glutamine Uptake

PubMed Central

Cheng, Zhihui; Lin, Mingqun

2014-01-01

ABSTRACT How the obligatory intracellular bacterium Ehrlichia chaffeensis begins to replicate upon entry into human monocytes is poorly understood. Here, we examined the potential role of amino acids in initiating intracellular replication. PutA converts proline to glutamate, and GlnA converts glutamate to glutamine. E. chaffeensis PutA and GlnA complemented Escherichia coli putA and glnA mutants. Methionine sulfoximine, a glutamine synthetase inhibitor, inhibited E. chaffeensis GlnA activity and E. chaffeensis infection of human cells. Incubation of E. chaffeensis with human cells rapidly induced putA and glnA expression that peaked at 24 h postincubation. E. chaffeensis took up proline and glutamine but not glutamate. Pretreatment of E. chaffeensis with a proline transporter inhibitor (protamine), a glutamine transporter inhibitor (histidine), or proline analogs inhibited E. chaffeensis infection, whereas pretreatment with proline or glutamine enhanced infection and upregulated putA and glnA faster than no treatment or glutamate pretreatment. The temporal response of putA and glnA expression was similar to that of NtrY and NtrX, a two-component system, and electrophoretic mobility shift assays showed specific binding of recombinant E. chaffeensis NtrX (rNtrX) to the promoter regions of E. chaffeensis putA and glnA. Furthermore, rNtrX transactivated E. chaffeensis putA and glnA promoter-lacZ fusions in E. coli. Growth-promoting activities of proline and glutamine were also accompanied by rapid degradation of the DNA-binding protein CtrA. Our results suggest that proline and glutamine uptake regulates putA and glnA expression through NtrY/NtrX and facilitates degradation of CtrA to initiate a new cycle of E. chaffeensis growth. PMID:25425236

Uptake and elimination of poliovirus by West Coast oysters.

PubMed

Di Girolamo, R; Liston, J; Matches, J

1975-02-01

Accumulation of poliovirus Lsc-2ab by West Coast oysters was determined by using a stationary seawater system, and depuration was determined by using both stationary and free-flow systems. Results indicate that these shellfish have the same pattern of accumulation and localization of viruses as do East Coast species. However, uptake appeared to occur more rapidly than described for East Coast shellfish. There appeared to be a gradual diffusion of virus from the digestive area into the body. Depuration was found to occur more rapidly and completely under free-flow conditions than in a stationary system.

Uptake and Elimination of Poliovirus by West Coast Oysters

PubMed Central

Girolamo, Rudolph Di; Liston, John; Matches, J.

1975-01-01

Accumulation of poliovirus Lsc-2ab by West Coast oysters was determined by using a stationary seawater system, and depuration was determined by using both stationary and free-flow systems. Results indicate that these shellfish have the same pattern of accumulation and localization of viruses as do East Coast species. However, uptake appeared to occur more rapidly than described for East Coast shellfish. There appeared to be a gradual diffusion of virus from the digestive area into the body. Depuration was found to occur more rapidly and completely under free-flow conditions than in a stationary system. PMID:163615

Comparative analysis of nitrite uptake and hemoglobin-nitrite reactions in erythrocytes: sorting out uptake mechanisms and oxygenation dependencies.

PubMed

Jensen, Frank B; Rohde, Sabina

2010-04-01

Nitrite uptake into red blood cells (RBCs) precedes its intracellular reactions with hemoglobin (Hb) that forms nitric oxide (NO) during hypoxia. We investigated the uptake of nitrite and its reactions with Hb at different oxygen saturations (So(2)), using RBCs with (carp and rabbit) and without (hagfish and lamprey) anion exchanger-1 (AE1) in the membrane, with the aim to unravel the mechanisms and oxygenation dependencies of nitrite transport. Added nitrite rapidly diffused into the RBCs until equilibrium. The distribution ratio of nitrite across the membrane agreed with that expected from HNO(2) diffusion and AE1-mediated facilitated NO(2)(-) diffusion. Participation of HNO(2) diffusion was emphasized by rapid transmembrane nitrite equilibration also in the natural AE1 knockouts. Following the equilibration, nitrite was consumed by reacting with Hb, which created a continued inward diffusion controlled by intracellular reaction rates. Changes in nitrite uptake with So(2), pH, or species were accordingly explained by corresponding changes in reaction rates. In carp, nitrite uptake rates increased linearly with decreasing So(2) over the entire So(2) range. In rabbit, nitrite uptake rates were highest at intermediate So(2), producing a bell-shaped relationship with So(2). Nitrite consumption increased approximately 10-fold with a 1 unit decrease in pH, as expected from the involvement of protons in the reactions with Hb. The reaction of nitrite with deoxyhemoglobin was favored over that with oxyhemoglobin at intermediate So(2). We propose a model for RBC nitrite uptake that involves both HNO(2) diffusion and AE1-mediated transport and that explains both the present and previous (sometimes puzzling) results.

Methylcellulose-Directed Synthesis of Nanocrystalline Zeolite NaA with High CO₂ Uptake.

PubMed

Shakarova, Dilshod; Ojuva, Arto; Bergström, Lennart; Akhtar, Farid

2014-07-28

Zeolite NaA nanocrystals with a narrow particle size distribution were prepared by template-free hydrothermal synthesis in thermo-reversible methylcellulose gels. The effects of the amount of methylcellulose, crystallization time and hydrothermal treatment temperature on the crystallinity and particle size distribution of the zeolite NaA nanocrystals were investigated. We found that the thermogelation of methylcellulose in the alkaline Na₂O-SiO₂-Al₂O₃-H₂O system played an important role in controlling the particle size. The synthesized zeolite nanocrystals are highly crystalline, as demonstrated by X-ray diffraction (XRD), and scanning electron microscopy (SEM) shows that the nanocrystals can also display a well-defined facetted morphology. Gas adsorption studies on the synthesized nanocrystalline zeolite NaA showed that nanocrystals with a size of 100 nm displayed a high CO₂ uptake capacity (4.9 mmol/g at 293 K at 100 kPa) and a relatively rapid uptake rate compared to commercially available, micron-sized particles. Low-cost nanosized zeolite adsorbents with a high and rapid uptake are important for large scale gas separation processes, e.g., carbon capture from flue gas.

Decadal predictions of the North Atlantic CO2 uptake.

PubMed

Li, Hongmei; Ilyina, Tatiana; Müller, Wolfgang A; Sienz, Frank

2016-03-30

As a major CO2 sink, the North Atlantic, especially its subpolar gyre region, is essential for the global carbon cycle. Decadal fluctuations of CO2 uptake in the North Atlantic subpolar gyre region are associated with the evolution of the North Atlantic Oscillation, the Atlantic meridional overturning circulation, ocean mixing and sea surface temperature anomalies. While variations in the physical state of the ocean can be predicted several years in advance by initialization of Earth system models, predictability of CO2 uptake has remained unexplored. Here we investigate the predictability of CO2 uptake variations by initialization of the MPI-ESM decadal prediction system. We find large multi-year variability in oceanic CO2 uptake and demonstrate that its potential predictive skill in the western subpolar gyre region is up to 4-7 years. The predictive skill is mainly maintained in winter and is attributed to the improved physical state of the ocean.

Hepatitis A and B vaccination--the rate of uptake and course completion in patients with hepatitis C.

PubMed

Fredericks, Trinity; Kwan, Kellie; Mak, Donna

2010-10-01

Western Australian general practitioners may order Department of Health funded hepatitis A and B vaccines for patients newly notified with hepatitis C to prevent complications associated with co-infections. The aim of this study was to determine vaccination uptake of hepatitis C patients through this program. We reviewed hepatitis C notifications and hepatitis A and B vaccine orders received in 2007 and 2008 to determine the rate of vaccine uptake and course completion. Vaccination orders for initial doses were received for 37% (448/1209) of patients. Vaccination uptake was positively associated with age and non- Aboriginality. Final vaccination doses were ordered for 30% of patients for whom an initial order had been received. Uptake of hepatitis A and B vaccination was higher than that of similar populations. However, vaccination course completion was low. General practitioners need to emphasise to their patients the importance of completing a vaccine course.

Sucrose uptake by pinocytosis in Amoeba proteus and the influence of external calcium

PubMed Central

1979-01-01

The relationship between Ca++ and pinocytosis was investigated in Amoeba proteus. Pinocytosis was induced with 0.01% alcian blue, a large molecular weight dye which binds irreversibly to the cell surface. The time-course and intensity of pinocytosis was monitored by following the uptake of [3H]SUCROSE. When the cells are exposed to 0.01% alcian blue, there is an immediate uptake of sucrose. The cells take up integral of 10% of their initial volume during the time-course of pinocytosis. The duration of pinocytosis in the amoeba is integral of 50 min, with maximum sucrose uptake occurring 15 min after the induction of pinocytosis. The pinocytotic uptake of sucrose is reversibly blocked at 3 degrees C and a decrease in pH increases the uptake of sucrose by pinocytosis. The process of pinocytosis is also dependent upon the concentration of the inducer in the external medium. The association between Ca++ and pinocytosis in A. proteus was investigated initially by determining the effect of the external Ca++ concentration on sucrose uptake induced by alcian blue. In Ca++-free medium, no sucrose uptake is observed in the presence of 0.01% alcian blue. As the Ca++ concentration is increased, up to a maximum of 0.1 mM, pinocytotic sucrose uptake is also increased. Increases in the external Ca++ concentration above 0.1 mM brings about a decrease in sucrose uptake. Further investigations into the association between Ca++ and pinocytosis demonstrated that the inducer of pinocytosis displaces surface calcium in the amoeba. It is suggested that Ca++ is involved in two separate stages in the process of pinocytosis; an initial displacement of surface calcium by the inducer which may increase the permeability of the membrane to solutes and a subsequent Ca++ influx bringing about localized increases in cytoplasmic Ca++ ion activity. PMID:512629

Increasing Healthy Start food and vitamin voucher uptake for low income pregnant women (Early Years Collaborative Leith Pioneer Site).

PubMed

Mackenzie, Graham; Dougall, Angela

2016-01-01

Poverty has a detrimental impact on health and wellbeing. Healthy Start food and vitamin vouchers provide support for low income families across the UK, but at least 25% of eligible women and children miss out. We set out to increase uptake, with an aim of 90% of eligible women and children (n~540 eligible, varying over time) receiving vouchers in the initial team's catchment area by December 2015. Starting with one midwife and one pregnant woman in March 2014 we used the model for improvement to identify ways to improve documentation, sign up, and referral. Weekly data on process measures and monthly data on voucher receipt were plotted on run charts. Comparing medians for January-June 2014 and March-August 2015 there was a 13.3% rise in voucher receipt in Lothian (increase from 313 to 355 women), versus an 8.4% decline for the rest of Scotland (fall from 1688 to 1546 women). Figures varied by team, influenced by staff, family, and area factors. The initial aim proved unrealistic, as signing up a woman for vouchers increases both the numerator and denominator. Accordingly, the percentage uptake has not increased at a regional level (remains at 75%), though the figure for the initiating team ("team 3" in graphs) has increased from 73.0% (January 2014) to 79.0% (November 2015). We have continued testing, achieving recent increases in the number of women referred for welfare rights advice on benefits, tax credits, employment rights, childcare, and debt, securing on average £4,500 per client during 2015/16 (£404k for 89 clients by mid September 2015). This improvement project, part of the Early Years Collaborative in Scotland, has had a measureable impact on pregnant women across Lothian. Success has relied on testing, an electronic maternity record, rapid dissemination of findings through direct engagement with clinical teams, and persistence. Our findings have relevance across the UK, particularly at a time of worsening finances for many families.

Hepatic uptake and biliary excretion of manganese in the little skate, Leucoraja erinacea.

PubMed

Madejczyk, Michael S; Boyer, James L; Ballatori, Nazzareno

2009-05-01

The liver is a major organ involved in regulating whole body manganese (Mn) homeostasis; however, the mechanisms of Mn transport across the hepatocyte basolateral and canalicular membranes remain poorly defined. To gain insight into these transport steps, the present study measured hepatic uptake and biliary excretion of Mn in an evolutionarily primitive marine vertebrate, the elasmobranch Leucoraja erinacea, the little skate. Mn was rapidly removed from the recirculating perfusate of isolated perfused skate livers in a dose-dependent fashion; however, only a small fraction was released into bile (<2% in 6 h). Mn was also rapidly taken up by freshly isolated skate hepatocytes in culture. Mn uptake was inhibited by a variety of divalent metals, but not by cesium. Analysis of the concentration-dependence of Mn uptake revealed of two components, with apparent K(m) values 1.1+/-0.1 microM and 112+/-29 microM. The K(m) value for the high-affinity component was similar to the measured skate blood Mn concentration, 1.9+/-0.5 microM. Mn uptake was reduced by nearly half when bicarbonate was removed from the culture medium, but was unaffected by a change in pH from 6.5 to 8.5, or by substitution of Na with Li or K. Mn efflux from the hepatocytes was also rapid, and was inhibited when cells were treated with 0.5 mM 2,4-dinitrophenol to deplete ATP levels. These data indicate that skate liver has efficient mechanisms for removing Mn from the sinusoidal circulation, whereas overall biliary excretion is low and appears to be mediated in part by an ATP-sensitive mechanism.

Hepatic uptake and biliary excretion of manganese in the little skate, Leucoraja erinacea

PubMed Central

Madejczyk, Michael S.; Boyer, James L.; Ballatori, Nazzareno

2008-01-01

The liver is a major organ involved in regulating whole body manganese (Mn) homeostasis; however, the mechanisms of Mn transport across the hepatocyte basolateral and canalicular membranes remain poorly defined. To gain insight into these transport steps, the present study measured hepatic uptake and biliary excretion of Mn in an evolutionarily primitive marine vertebrate, the elasmobranch Leucoraja erinacea, the little skate. Mn was rapidly removed from the recirculating perfusate of isolated perfused skate livers in a dose-dependent fashion; however, only a small fraction was released into bile (<2% in 7h). Mn was also rapidly taken up by freshly isolated skate hepatocytes in culture. Mn uptake was inhibited by a variety of divalent metals, but not by cesium. Analysis of the concentration-dependence of Mn uptake revealed of two components, with apparent Km values 1.1 ± 0.1 μM and 112 ± 29 μM. The Km value for the high-affinity component was similar to the measured skate blood Mn concentration, 1.9 ± 0.5 μM. Mn uptake was reduced by nearly half when bicarbonate was removed from the culture medium, but was unaffected by a change in pH from 6.5 to 8.5, or by substitution of Na with Li or K. Mn efflux from the hepatocytes was also rapid, and was inhibited when cells were treated with 0.5 mM 2,4-dinitrophenol to deplete ATP levels. These data indicate that skate liver has efficient mechanisms for removing Mn from the sinusoidal circulation, whereas overall biliary excretion is low and appears to be mediated in part by an ATP-sensitive mechanism. PMID:19141331

One-to-One Laptop Programs: Is Transformation Occurring in Mathematics Teaching?

ERIC Educational Resources Information Center

Blackley, Susan; Walker, Rebecca

2015-01-01

There is a body of research around the uptake of digital technologies in secondary schools, and a growing body of research specifically designed to investigate the use of one-to-one laptop programs. However this research focused on the initial uptake of the digital technology or initial implementation of a one-to-one (1:1) laptop policy. Given the…

Preparation and biologic evaluation of a novel radioiodinated benzylpiperazine, 123I-MEL037, for malignant melanoma.

PubMed

Pham, Tien Q; Berghofer, Paula; Liu, Xiang; Greguric, Ivan; Dikic, Branko; Ballantyne, Patrice; Mattner, Filomena; Nguyen, Vu; Loc'h, Christian; Katsifis, Andrew

2007-08-01

Radiopharmaceuticals that can target the random metastatic dissemination of melanoma tumors may present opportunities for imaging and staging the disease as well as potential radiotherapeutic applications. A novel molecule, 2-(2-(4-(4-(123)I-iodobenzyl)piperazin-1-yl)-2-oxoethyl)isoindoline-1,3-dione (MEL037), was synthesized, labeled with 123I, and evaluated for application in melanoma tumor scintigraphy and radiotherapy. The tumor imaging potential of 123I-MEL037 was studied in vivo in C57BL/6J female mice bearing the B16F0 murine melanoma tumor and in BALB/c nude mice bearing the A375 human amelanotic melanoma tumor by biodistribution, competition studies, and SPECT. 123I-MEL037 exhibited high and rapid uptake in the B16F0 melanoma tumor at 1 h (13 %ID/g [percentage injected dose per gram]), increasing with time to reach 25 %ID/g at 6 h. A significant uptake was also observed in the eyes (2 %ID, at 3-6 h after injection) of black mice. No uptake was observed in the tumor or in the eyes of nude mice bearing the A375 tumor. Because of high uptake and long retention in the tumor and rapid body clearance, the mean contrast ratios (MCR) of 123I-MEL037 were 30 and 60, at 24 and 48 h after injection, respectively. At 24 h after injection of mice bearing the B16 melanoma, SPECT indicated that the radioactivity was located predominately in the tumor followed by the eyes, whereas no specific localization of the radioactivity was noted in mice bearing the A375 human amelanotic tumor. In competition experiments, uptake of 123I-MEL037 in brain, lung, heart, and kidney--organs known to contain sigma-receptors--was not significantly different in haloperidol-treated animals compared with control animals. Therefore, reduction of uptake in tumor and eyes of the pigmented mice bearing the B16F0 tumor suggested that the mechanism of tumor uptake was likely due to an interaction with melanin. These findings suggested that 123I-MEL037, which displays a rapid and very high tumor uptake, appeared to be a promising imaging agent for detection of most melanoma tumors with the potential for development as a therapeutic agent in melanoma tumor proliferation.

[Kinetics of uptake of phosphates and nitrates by marine multicellular algae Gelidium latifolium (Grev.) Born. et Thur].

PubMed

Silkin, V A; Chubchikova, I N

2007-01-01

We studied nonstationary kinetics of the uptake of phosphates and nitrates by the red marine algae Gelidium latifolium (Grev.) Born et Thur. and calculated constants of the Michaelis-Menten equation for these elements. In the area of 0-3 microM, the kinetics of phosphate consumption had the following coefficients: maximum rate of uptake 0.8 micromol/(g x h), constant of half-saturation 1.745 microM. For nitrate nitrogen at 0-30 microM, an adaptive strategy of uptake kinetics was noted with change of the equation parameters with time: after 1 h, the maximum rate of uptake was 5.1 micromol/(g x h) and constant of half-saturation 19 gM, while within 2 h, the maximum rate of uptake significantly increased. This could be related to the synthesis of nitrate reductase. Coupled with the uptake of nitrates, nonstationary kinetics of the release of nitrates in the surrounding medium had a one-peak pattern: the maximum concentration of nitrites in the medium and the time of its achievement increased with the initial concentration of nitrates. The maximum concentration of nitrites was 6 to 14% of the initial concentration in the medium.

A fluorescence method for determination of glucose transport by intestinal BBMV of common carp.

PubMed

Yang, Li-Ping; Yan, Xiao; Zheng, Wen-Jia; Hu, Jun-Yi; Zhang, Yu-Ru; Qin, Chao-Bin; Meng, Xiao-Lin; Lu, Rong-Hua; Chen, Fang; Xie, Di-Zhi; Nie, Guo-Xing

2017-11-15

Epithelial brush-border membrane vesicles (BBMVs) were isolated from the intestine of common carp and studied systematically by enzyme activity, transmission electron microscopy and immunoblotting. The uptake time course and the substrate concentration effect were assessed, and then, the ability of phlorizin and cytochalasin B to inhibit uptake was analyzed. The results show that sucrase, alkaline phosphatase and Na + -K + -ATPase activities in these vesicles were enriched 7.94-, 6.74- and 0.42-fold, respectively, indicating a relatively pure preparation of apical membrane with little basolateral contamination. The vesicular structure was in complete closure, as confirmed by electron microscopy. The presence of SGLT1 on the BBMVs was confirmed by Western blot analysis. In the time course experiment, the glucose uptake by BBMVs in Na + medium displayed an initial accumulation (overshoot) at 5 min followed by a rapid return to equilibrium values at 60 min. Over the 2-NBDG concentration range selected, the external 2-NBDG concentration in NaSCN medium graphed as a curved line. Phlorizin and cytochalasin B had an obvious inhibitory effect on 2-NBDG transport in carp BBMVs, and the detected fluorescence intensity decreased. The inhibition rate in the 1000 μM group was the strongest at 64.18% and 63.61% of phlorizin and cytochalasin B, respectively, indicating the presence of carriers other than SGLT1. This study is the first to demonstrate that 2-NBDG can be used as a convenient and sensitive probe to detect glucose uptake in fish BBMVs. This technology will provide a convenient method to discover new effects and factors in glucose metabolism. Copyright © 2017. Published by Elsevier Inc.

99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours.

PubMed

von Guggenberg, E; Dietrich, H; Skvortsova, I; Gabriel, M; Virgolini, I J; Decristoforo, C

2007-08-01

Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA(0),D: Glu(1)]minigastrin (DTPA-MG0) radiolabelled with (111)In and (90)Y, our group developed a (99m)Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC(0),D: Glu(1),desGlu(2-6)]minigastrin (HYNIC-MG11). (99m)Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. (99m)Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of (99m)Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. (99m)Tc-EDDA-HYNIC-MG11 shows advantages over (99m)Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement.

Assessing patients' attitudes to opt-out HIV rapid screening in community dental clinics: a cross-sectional Canadian experience.

PubMed

Brondani, Mario; Chang, Steve; Donnelly, Leeann

2016-05-10

As a public health initiative, provided-initiated HIV screening test in dental settings has long been available in the U.S.; it was only in 2011 that such setting was used in Canada. The objective of this paper was to assess patients' response to, and attitudes towards, an opt-out rapid HIV screening test in a dental setting in Vancouver, Canada. A cross-sectional evaluation design using a self-complete survey questionnaire on self-perceived values and benefits of an opt-out rapid HIV screening was employed. An anonymous 10-item questionnaire was developed to explore reasons for accepting or declining the HIV rapid screening test, and barriers and facilitators for the HIV screening in dental settings. Eligible participants were male and female older than 19 years attending community dental clinics and who were offered the HIV screening test between June 2010 and February 2015. From the 1552 age-eligible patients, 519 completed the survey and 155 (10 %) accepted the HIV screening due to its convenience, and/or free cost, and/or instant results. From the 458 respondents who did not accept the screening, 362 (79 %) were between the ages of 25 and 45 years; 246 (53.7 %) had identifiable risk factors for contracting HIV; and 189 (41.3 %) reported having been tested within the last 3 months. Those tested in less than 3 months had 3.5 times higher odds to decline the HIV screening compared to those who have been tested between 3 months and 1 year. Convenience, cost-free and readily available results are factors influencing rapid HIV screening uptake. Although dental settings remain an alternative venue for HIV screening from the patients' perspectives, dental hygiene settings might offer a better option.

Research Paper. Nutrient uptake and mineralization during leaf decay in streams-a model simulation.

Treesearch

J.R. Webster; J.D. Newbold; S.A. Thomas; H.M. Valett; P.J. Mulholland

2009-01-01

We developed a stoichiometrically explicit computer model to examine how heterotrophic uptake of nutrients and microbial mineralization occurring during the decay of leaves in streams may be important in modifying nutrient concentrations. The simulations showed that microbial uptake can substantially decrease stream nutrient concentrations during the initial phases of...

MTBE inhaled alone and in combination with gasoline vapor: uptake, distribution, metabolism, and excretion in rats.

PubMed

Benson, J M; Barr, E B; Krone, J R

2001-05-01

The purpose of these studies was to extend previous evaluation of methyl tert-butyl ether (MTBE)* tissue distribution, metabolism, and excretion in rats to include concentrations more relevant to human exposure (4 and 40 ppm) and to determine the effects of coinhalation of the volatile fraction of unleaded gasoline on the tissue distribution, metabolism, and excretion of MTBE. Groups of male F344 rats were exposed nose-only for 4 hours to 4, 40, or 400 ppm 14C-MTBE or to 20 or 200 ppm of the light fraction of unleaded gasoline (LFG) containing 4 or 40 ppm 14C-MTBE, respectively. To evaluate the effects of repeated inhalation of LFG on MTBE tissue distribution, metabolism, and excretion, rats were exposed for 4 hours on each of 7 consecutive days to 20 or 200 ppm LFG with MTBE (4 or 40 ppm) followed on the eighth day by a similar exposure to LFG containing 14C-MTBE. Subgroups of rats were evaluated for respiratory parameters, initial body burdens, rates and routes of excretion, and tissue distribution and elimination. The concentrations of MTBE and its chief metabolite, tert-butyl alcohol (TBA), were measured in blood and kidney immediately after exposure, and the major urinary metabolites-2-hydroxyisobutyric acid (IBA) and 2-methyl-1,2-propanediol (2MePD)-were measured in urine. Inhalation of MTBE alone or as a component of LFG had no concentration-dependent effect on respiratory minute volume. The initial body burdens of MTBE equivalents achieved after 4 hours of exposure to MTBE did not increase linearly with exposure concentration. MTBE equivalents rapidly distributed to all tissues examined, with the largest percentages distributed to liver. The observed initial body burden did not increase linearly between 4 and 400 ppm. At 400 ppm, elimination half-times of MTBE equivalents from liver increased and from lung, kidney, and testes decreased compared with the two smaller doses. Furthermore, at 400 ppm the elimination half-time for volatile organic compounds (VOCs) in breath was significantly shorter and the percentage of the initial body burden of MTBE equivalents eliminated as VOCs in breath increased significantly. These changes probably reflect a saturation of blood with MTBE at 400 ppm and strongly suggest that the uptake and fate of MTBE are notably different at exposure concentrations above and below 400 ppm. Single and repeated coexposure to 20 and 200 ppm LFG with MTBE had opposite effects on the total body burden of MTBE equivalents present at the end of exposures compared with those achieved after 4 and 40 ppm MTBE exposures: 20 ppm LFG increased and 200 ppm LFG significantly decreased the burdens of MTBE equivalents present. The effects of coexposure to LFG on blood levels of MTBE equivalents paralleled the effects on body burden. These differences in overall uptake of MTBE equivalents cannot be attributed to alterations of minute volume. The reason for the increase in overall uptake after 20-ppm LFG exposure is not clear. Decreased MTBE absorption (uptake) after single and repeated coexposure to 200 ppm LFG may be due to a decrease in solubility of MTBE in blood caused by inhalation of other hydrocarbons. Investigations on the blood/air partition coefficient of MTBE in the absence and presence of LFG would be needed to confirm this hypothesis. Single and repeated coexposure to either 20 or 200 ppm LFG significantly decreased the percentage of the initial body burden from MTBE equivalents in tissues, including liver, kidney, and testes, immediately and 72 hours after

Efficacy of superficial temporal artery-middle cerebral artery double anastomoses in a patient with rapidly progressive moyamoya disease: case report.

PubMed

Yokosawa, Michiko; Hayashi, Toshiaki; Shirane, Reizo; Tominaga, Teiji

2014-01-01

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction.

Efficacy of Superficial Temporal Artery-Middle Cerebral Artery Double Anastomoses in a Patient with Rapidly Progressive Moyamoya Disease: Case Report

PubMed Central

YOKOSAWA, Michiko; HAYASHI, Toshiaki; SHIRANE, Reizo; TOMINAGA, Teiji

2014-01-01

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction. PMID:24584280

Uptake of VOC by sunflower

NASA Astrophysics Data System (ADS)

Folkers, A.; Miebach, M.; Kleist, E.; Wildt, J.

2003-04-01

To study potential VOC uptake by plants we exposed sunflower (Helianthus annuus) to different VOC in continuously stirred tank reactors. For many VOC like methanol, ethanol, acetone, methylvinylketone, isoprene or limonene no uptake was detectable within the accuracy of our analytic set up. Other VOC like hexanal, octanal, (E)-3-hexenol and nopinone were taken up by sunflower. The uptake was related to stomatal aperture. Obviously, these VOC enter the plants through stomata. In case of hexanal, octanal, and (E)-3-hexenol the uptake was only limited by stomatal aperture implying that these VOC are rapidly metabolised. For nopinone the uptake seems to be limited by a slow metabolization. Estimations of deposition velocities showed that dry deposition of these compounds cannot be neglected as sink if diffusion through stomata is the limiting step for dry deposition. In such cases the lifetime with respect to dry deposiotion is comparable to the lifetime with respect to oxidation by hydroxyl radicals.

Characteristics of injury and recovery of net NO3- transport of barley seedlings from treatments of NaCl

NASA Technical Reports Server (NTRS)

Klobus, G.; Ward, M. R.; Huffaker, R. C.

1988-01-01

The nature of the injury and recovery of nitrate uptake (net uptake) from NaCl stress in young barley (Hordeum vulgare L, var CM 72) seedlings was investigated. Nitrate uptake was inhibited rapidly by NaCl, within 1 minute after exposure to 200 millimolar NaCl. The duration of exposure to saline conditions determined the time of recovery of NO3- uptake from NaCl stress. Recovery was dependent on the presence of NO3- and was inhibited by cycloheximide, 6-methylpurine, and cerulenin, respective inhibitors of protein, RNA, and sterol/fatty acid synthesis. These inhibitors also prevented the induction of the NO3- uptake system in uninduced seedlings. Uninduced seedlings exhibited endogenous NO3- transport activity that appeared to be constitutive. This constitutive activity was also inhibited by NaCl. Recovery of constitutive NO3- uptake did not require the presence of NO3-.

Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM.

PubMed

Burgman, Paul; O'Donoghue, Joseph A; Lewis, Jason S; Welch, Michael J; Humm, John L; Ling, C Clifton

2005-08-01

Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) [Cu-ATSM] is a potential marker for tumor hypoxia that has been under evaluation for clinical use. In this study, we examined the mechanisms underlying the uptake of (64)Cu in cells incubated with (64)Cu-ATSM. The in vitro uptake of (64)Cu was determined as a function of oxygenation conditions and incubation time with (64)Cu-ATSM using four and two tumor cell lines of human origin and rodent origin, respectively. Additionally, the rate of (64)Cu efflux and Cu-ATSM metabolism was determined. (64)Cu accumulation is rapid during the first 0.5-1 h of incubation. It is highest in anoxic cells but is also significant in normoxic cells. After this initial period, the level of intracellular (64)Cu varies depending on the cell line and the oxygenation conditions and, in some circumstances, may decrease. During the first 0.5-1 h, the ratio of (64)Cu levels between anoxic and normoxic cells is approximately 2:10 and that between hypoxic (0.5% O(2)) and normoxic cells is approximately 1:2.5, depending on the cell line. These ratios generally decrease at longer times. The (64)Cu-ATSM compound was found to be metabolized during incubation in a manner dependent on oxygenation conditions. Within 2 h under anoxic conditions, (64)Cu-ATSM could no longer be detected, although 60-90% of the amount of (64)Cu added as (64)Cu-ATSM was present in the medium. Non-ATSM (64)Cu was taken up by the cells, albeit at a much slower rate. Efflux rates of (64)Cu were found to be cell line dependent and appeared to be inversely correlated with the final (64)Cu uptake levels under anoxic conditions. The uptake and retention of (64)Cu and their relation to oxygenation conditions were found to be cell line dependent. Given the complexities in the oxygen dependence and cell line-dependent kinetics of uptake and retention of Cu following exposure to Cu-ATSM, the clinical utility of this compound may be disease site specific.

Biodistribution and radiation dosimetry of LMI1195: first-in-human study of a novel 18F-labeled tracer for imaging myocardial innervation.

PubMed

Sinusas, Albert J; Lazewatsky, Joel; Brunetti, Jacqueline; Heller, Gary; Srivastava, Ajay; Liu, Yi-Hwa; Sparks, Richard; Puretskiy, Andrey; Lin, Shu-fei; Crane, Paul; Carson, Richard E; Lee, L Veronica

2014-09-01

A novel (18)F-labeled ligand for the norepinephrine transporter (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine [LMI1195]) is in clinical development for mapping cardiac nerve terminals in vivo using PET. Human safety, whole-organ biodistribution, and radiation dosimetry of LMI1195 were evaluated in a phase 1 clinical trial. Twelve healthy subjects at 3 clinical sites were injected intravenously with 150-250 MBq of LMI1195. Dynamic PET images were obtained over the heart for 10 min, followed by sequential whole-body images for approximately 5 h. Blood samples were obtained, and heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. Residence times were determined from multiexponential regression of organ region-of-interest data normalized by administered activity (AA). Radiation dose estimates were calculated using OLINDA/EXM. Myocardial, lung, liver, and blood-pool standardized uptake values were determined at different time intervals. No adverse events due to LMI1195 were seen. Blood radioactivity cleared quickly, whereas myocardial uptake remained stable and uniform throughout the heart over 4 h. Liver and lung activity cleared relatively rapidly, providing favorable target-to-background ratios for cardiac imaging. The urinary bladder demonstrated the largest peak uptake (18.3% AA), followed by the liver (15.5% AA). The mean effective dose was 0.026 ± 0.0012 mSv/MBq. Approximately 1.6% AA was seen in the myocardium initially, remaining above 1.5% AA (decay-corrected) through 4 h after injection. The myocardium-to-liver ratio was approximately unity initially, increasing to more than 2 at 4 h. These preliminary data suggest that LMI1195 is well tolerated and yields a radiation dose comparable to that of other commonly used PET radiopharmaceuticals. The kinetics of myocardial and adjacent organ activity suggest that cardiac imaging should be possible with acceptable patient radiation dose. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles

PubMed Central

Cho, Eun Chul; Zhang, Qiang; Xia, Younan

2011-01-01

In vitro experiments typically measure the uptake of nanoparticles by exposing cells at the bottom of a culture plate to a suspension of nanoparticles, which is assumed to be well-dispersed. However, nanoparticles can sediment and this means the concentration of particles on the cell surface and those actually taken up by the cells may be higher than the initial bulk concentration. Here we use upright and inverted cell culture configurations to show that cellular uptake of gold nanoparticles depends on the sedimentation and diffusion velocities of the nanoparticles and is independent of size, shape, density, surface coating and initial concentration of the nanoparticles. Generally more nanoparticles are taken up in the upright configuration than the inverted one and nanoparticles that sediment faster showed greater differences in uptake between the two configurations. Our results suggest that cellular uptake of nanoparticles is sensitive to the way cells are positioned and sedimentation need to be considered when performing in vitro studies for large and heavy nanoparticles. PMID:21516092

Optimizing simulated fertilizer additions using a genetic algorithm with a nutrient uptake model

Treesearch

Wendell P. Cropper; N.B. Comerford

2005-01-01

Intensive management of pine plantations in the southeastern coastal plain typically involves weed and pest control, and the addition of fertilizer to meet the high nutrient demand of rapidly growing pines. In this study we coupled a mechanistic nutrient uptake model (SSAND, soil supply and nutrient demand) with a genetic algorithm (GA) in order to estimate the minimum...

Bioaccessibility and Cellular Uptake of β-Carotene Encapsulated in Model O/W Emulsions: Influence of Initial Droplet Size and Emulsifiers

PubMed Central

Kelly, Alan L.

2017-01-01

The effects of the initial emulsion structure (droplet size and emulsifier) on the properties of β-carotene-loaded emulsions and the bioavailability of β-carotene after passing through simulated gastrointestinal tract (GIT) digestion were investigated. Exposure to GIT significantly changed the droplet size, surface charge and composition of all emulsions, and these changes were dependent on their initial droplet size and the emulsifiers used. Whey protein isolate (WPI)-stabilized emulsion showed the highest β-carotene bioaccessibility, while sodium caseinate (SCN)-stabilized emulsion showed the highest cellular uptake of β-carotene. The bioavailability of emulsion-encapsulated β-carotene based on the results of bioaccessibility and cellular uptake showed the same order with the results of cellular uptake being SCN > TW80 > WPI. An inconsistency between the results of bioaccessibility and bioavailability was observed, indicating that the cellular uptake assay is necessary for a reliable evaluation of the bioavailability of emulsion-encapsulated compounds. The findings in this study contribute to a better understanding of the correlation between emulsion structure and the digestive fate of emulsion-encapsulated nutrients, which make it possible to achieve controlled or potential targeted delivery of nutrients by designing the structure of emulsion-based carriers. PMID:28930195

The spontaneous and evoked release of spermine from rat brain in vitro.

PubMed Central

Harman, R. J.; Shaw, G. G.

1981-01-01

1 The efflux of previously accumulated [3H]-spermine from brain slices was measured using a continuous perfusion system. The spontaneous efflux was biphasic, consisting of an initial rapid efflux followed by a much slower release. 2 The slices were depolarized by the addition to the medium of high potassium concentrations, ouabain or veratrine. 3 At concentrations greater than 30 mM, potassium evoked a striking increase in the release of [3H]-spermine. Following uptake in the presence of 5.7 x 10(-9)M [3H]-spermine, K+-evoked release was dependent on the presence of calcium ions. Release of spermine after uptake at 5.6 x 10(-8)M or 5.0 x 10(-7)M was not calcium-dependent. 4 The calcium-dependent, K+-stimulated release of spermine was inhibited in the presence of diphenylhydantoin (5 x 10(-5)M) or ruthenium red (10(-5)M). 5 Following uptake of 5.7 x 10(-9)M [3H]-spermine in a sodium-free medium, the calcium-dependent, K+-stimulated release was significantly inhibited. 5 Ouabain (10(-4)M) caused a large but calcium-independent increase in the efflux of [3H]-spermine. 7 Veratrine-induced release was less substantial but was increased in a calcium-free medium. Release evoked by veratrine was abolished in the absence of sodium. 8 These results are discussed with respect to a possible 'neurotransmitter' or 'neuromodulator' role for spermine. PMID:6169383

Effect of stopper processing conditions on moisture content and ramifications for lyophilized products: comparison of "low" and "high" moisture uptake stoppers.

PubMed

Donovan, P D; Corvari, V; Burton, M D; Rajagopalan, N

2007-01-01

The purpose of this study was to evaluate the effect of processing and storage on the moisture content of two commercially available, 13-mm lyophilization stoppers designated as low moisture (LM) and high moisture (HM) uptake stoppers. The stopper moisture studies included the effect of steam sterilization time, drying time and temperature, equilibrium moisture content, lyophilization and moisture transfer from stopper to a model-lactose lyophilized cake. Results indicated that both stoppers absorbed significant amounts of moisture during sterilization and that the HM stopper absorbed significantly more water than the LM stopper. LM and HM stoppers required approximately 2 and 8 h drying at 105 degrees C, respectively, to achieve final moisture content of not more than 0.5 mg/stopper. Following drying, stopper moisture levels equilibrated rapidly to ambient storage conditions. The apparent equilibrium moisture level was approximately 7 times higher in the HM versus LM stopper. Freeze-drying had minimal effect on the moisture content of dried stoppers. Finally, moisture transfer from the stopper to the lyophilized product is dependent on the initial stopper water content and storage temperature. To better quantify the ramifications of stopper moisture, projections of moisture uptake over the shelf life of a drug product were calculated based on the product-contact surface area of stoppers. Attention to stopper storage conditions prior to use, in addition to processing steps, are necessary to minimize stability issues especially in low-fill, mass lyophilized products.

Tests of bioaccumulation models for polychlorinated biphenyl compounds: a study of young-of-the-year bluefish in the Hudson River estuary, USA.

PubMed

Leblanc, Lawrence A; Buckel, Jeffrey A; Conover, David O; Brownawell, Bruce J

2006-08-01

A field-based study regarding uptake of polychlorinated biphenyl compounds (PCBs) by young-of-the-year (YOY) bluefish (Pomatomus saltatrix) was initiated to test a steady-state model of bioaccumulation and trophic transfer in a rapidly growing fish. Determination of prey composition as well as size-dependent growth and specific consumption rates for YOY bluefish from separate field and laboratory studies enabled the input of these species-specific parameters into the model. Furthermore, the time and duration of the exposure of YOY bluefish to dissolved PCBs from a well-characterized system (Hudson River, USA) was well known. Patterns of accumulation of individual PCB congeners differed relative to the accumulation of total PCBs, with the greatest net accumulation occurring for the higher-molecular-weight congeners. Comparison of lipid-normalized bioaccumulation factors (BAFs) with the octanol-water partition coefficients of individual PCB congeners revealed bluefish to be above the BAFs predicted by lipid-based equilibrium partitioning, suggesting that uptake from food is an important source of PCBs in YOY bluefish. Comparison of measured BAFs with values predicted by a steady-state, food-chain model showed good first-order agreement.

Influence of antigen on immune complex behavior in mice.

PubMed

Finbloom, D S; Magilavy, D B; Harford, J B; Rifai, A; Plotz, P H

1981-07-01

To explore the possibility that the behavior of immune complexes can, under some circumstances, be directed by the antigen, we have studied the behavior of complexes of identical size made with the glycoproteins, orosomucoid (OR), and ceruloplasmin: or with their desialylated derivatives, asialo-orosomucoid (ASOR) and asialo-ceruloplasmin. Such desialylated proteins are rapidly removed from the circulation by a hepatic cell receptor for galactose, the sugar exposed upon removal of sialic acid. Mixtures of 125I-goat anti-ASOR with either ASOR or OR and mixtures of 125I-rabbit anti-OR with either ASOR or OR form complexes identically. The complexes were separated by density gradient centrifugation and injected intravenously into C3H mice. Blood clearance and hepatic uptake of the OR complexes and ASOR complexes were markedly different. T 1/2 for the goat OR complexes exceeded 300 min, whereas that for the ASOR complexes was 15 min. More detailed studies using rabbit complexes of various sizes revealed that light rabbit complexes behaved similarly to the goat complexes. The light rabbit OR complexes were cleared slowly, with only 18% found in the liver at 60 min, whereas the light rabbit ASOR complexes were cleared much more rapidly, with 62% found within the liver by 30 min. This rapid clearance was completely suppressed by a prior injection of a blocking dose of ASOR, which implies uptake by a galactose-mediated mechanism on hepatocytes. As the size of the rabbit complexes increased, so did the rate of Fc receptor-mediated clearance. Heavy rabbit OR complexes were cleared more rapidly than light OR complexes but not so rapidly as heavy ASOR complexes. The clearance and hepatic uptake of the heavy OR complexes were markedly suppressed by a prior injection of heat-aggregated gamma globulin, a known Fc receptor-blocking agent (45% hepatic uptake without and 6% with aggregated gamma globulin). The heavy rabbit ASOR complexes exhibited inhibition of blood clearance and hepatic uptake by both galactose receptor-blocking and Fc receptor-blocking agents. A blocking dose of ASOR reduced the hepatic uptake at 30 min from 75 to 49%, and heat-aggregated gamma globulin reduced it from 75 to 39%, which suggests that these heavy complexes were removed from the circulation by receptors both for the immunoglobulin and for the antigen. Cell separation studies and autoradiographs confirmed that those complexes cleared primarily by galactose-mediated mechanism were within hepatocytes, and those cleared by Fc receptors were within the nonparenchymal cells of the liver. It seems probable, therefore, the some antigen-antibody complexes may be removed from the circulation via receptors not only for immunoglobulin but also for antigen.

STUDIES ON RESPIRATION, ANESTHESIA, AND RESUSCITATION.

DTIC Science & Technology

methoxyflurane were administered initially in vapor doses reported by others to meet anesthetic uptake requirements. Calculations of uptake...quantitative methoxyflurane anesthesia, blood concentrations were linearly correlated with intraocular pressure. The correlation of electro-encephalographic

Solute-specific scaling of inorganic nitrogen and phosphorus uptake in streams

NASA Astrophysics Data System (ADS)

Hall, R. O., Jr.; Baker, M. A.; Rosi-Marshall, E. J.; Tank, J. L.; Newbold, J. D.

2013-11-01

Stream ecosystem processes such as nutrient cycling may vary with stream position in the network. Using a scaling approach, we examined the relationship between stream size and nutrient uptake length, which represents the mean distance that a dissolved solute travels prior to removal from the water column. Ammonium (NH4+) uptake length increased proportionally with stream size measured as specific discharge (discharge/stream width) with a scaling exponent = 1.01. In contrast, uptake lengths for nitrate (NO3-) and soluble reactive phosphorus (SRP) increased more rapidly than increases in specific discharge (scaling exponents = 1.19 for NO3- and 1.35 for SRP). Additionally, the ratio of inorganic nitrogen (N) uptake length to SRP uptake length declined with stream size; there was relatively lower demand for SRP compared to N as stream size increased. Finally, we related the scaling of uptake length with specific discharge to that of stream length using Hack's law and downstream hydraulic geometry. Ammonium uptake length increased less than proportionally with distance from the headwaters, suggesting a strong role for larger streams and rivers in regulating nutrient transport.

Temperature shock, injury and transient sensitivity to nisin in Gram negatives.

PubMed

Boziaris, I S; Adams, M R

2001-10-01

The effect of thermal stresses on survival, injury and nisin sensitivity was investigated in Salmonella Enteritidis PT4, PT7 and Pseudomonas aeruginosa. Heating at 55 degrees C, rapid chilling to 0.5 degrees C or freezing at -20 degrees C produced transient sensitivity to nisin. Cells were only sensitive if nisin was present during stress. Resistance recovered rapidly afterwards, though some cells displayed residual injury. Injury was assessed by SDS sensitivity, hydrophobicity changes, lipopolysaccharide release and NPN uptake. LPS release and hydrophobicity were not always associated with transient nisin sensitivity. Uptake of NPN correlated better but persisted longer after treatment. Thermal shocks produce transient injury to the outer membrane, allowing nisin access. After treatment, the permeability barrier is rapidly restored by a process apparently involving reorganization rather than biosynthetic repair. Inclusion of nisin during food treatments that impose sub-lethal stress on Gram negatives could increase process lethality, enhancing microbiological safety and stability.

Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging.

PubMed

Onda, Nobuhiko; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

2016-08-01

Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. © 2016 UICC.

Uptake of Free HPV Vaccination among Young Women: A Comparison of Rural versus Urban Rates

ERIC Educational Resources Information Center

Crosby, Richard A.; Casey, Baretta R.; Vanderpool, Robin; Collins, Tom; Moore, Gregory R.

2011-01-01

Purpose: To contrast rates of initial HPV vaccine uptake, offered at no cost, between a rural clinic, a rural community college, and an urban college clinic and to identify rural versus urban differences in uptake of free booster doses. Methods: Young rural women attending rural clinics (n = 246), young women attending a rural community college (n…

Ascorbate oxidation is a prerequisite for its transport into rat liver microsomal vesicles.

PubMed Central

Csala, M; Mile, V; Benedetti, A; Mandl, J; Bánhegyi, G

2000-01-01

Oxidation and uptake of ascorbate show similar time courses in rat liver microsomal vesicles: a rapid burst phase is followed by a slower process. Inhibitors of ascorbate oxidation (proadifen, econazole or quercetin) also effectively decreased the uptake of ascorbate. The results show that dehydroascorbate is the transport form of ascorbate at the membrane of the endoplasmic reticulum. PMID:10880339

Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node

PubMed Central

Srinivasan, Swetha; Vannberg, Fredrik O.; Dixon, J. Brandon

2016-01-01

It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells’ functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response. PMID:27087234

Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

PubMed

Srinivasan, Swetha; Vannberg, Fredrik O; Dixon, J Brandon

2016-04-18

It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

Evaluation of neonicotinoid, organophosphate and avermectin trunk injections for the management of avocado thrips in California avocado groves.

PubMed

Byrne, Frank J; Urena, Anthony A; Robinson, Lindsay J; Krieger, Robert I; Doccola, Joe; Morse, Joseph G

2012-05-01

Trunk injections of systemic insecticides were evaluated for the management of avocado thrips. Insecticide residues were quantified in leaves to determine when after treatment, and for how long, toxic concentrations of the insecticides were present. Residues in fruit were quantified to determine whether trunk injection of insecticides might present a greater risk than traditional application methods for contaminating fruit. Residues of imidacloprid and dinotefuran were at least tenfold higher in leaves when trees were treated via trunk injection compared with soil application. Dinotefuran uptake was more rapid than imidacloprid, and no residues were detected within fruit. Acephate was also mobilized very rapidly and gave good control of thrips in bioassays; however, residues of acephate and its insecticidal metabolite methamidophos were detected in the fruit for up to 4 weeks after injection. Avermectin uptake was very slow, and it was ineffective against avocado thrips. Trunk injections of acephate and dinotefuran permitted rapid uptake into avocados, and they are strong candidates as control methods for avocado thrips. However, residues of organophosphates in fruit could necessitate increased preharvest intervals. Residues of neonicotinoids were below detection limits in fruit, suggesting that neonicotinoids may be the more suitable control option of the two chemical classes. Copyright © 2012 Society of Chemical Industry.

Opportunities for strengthening provider-initiated testing and counselling for HIV in Namibia

PubMed Central

Davyduke, Tracy; Pietersen, Ismelda; Lowrance, David; Amwaama, Selma; Taegtmeyer, Miriam

2015-01-01

This short report identifies enablers and barriers to the uptake of provider-initiated testing and counselling for HIV (PITC) in Namibia and identifies key opportunities for strengthening this vital aspect of the national HIV response. We explored this through facility mapping, register reviews and qualitative methods including focus group discussions and in-depth interviews. Four health facilities (clinics and hospitals) in two regions were included in the study. We identified that PITC in Namibia was largely delivered by lay counsellors operating in designated rapid testing rooms located in health facilities and found a large number of missed opportunities for HIV testing through this model. Nurses did not see it as an integral part of their role, were not aware of HIV testing and counselling policy, felt inadequately trained and supported, and experienced staffing shortages. Institutional issues also acted as barriers to nurses performing or initiating discussions about PITC. Wider dissemination and implementation of policy, increasing privacy of consultation spaces and community sensitisation are simple measures that represent opportunities for strengthening this response and ensuring that symptomatic individuals who are unaware of their HIV status do not fall through the net. PMID:25771903

Arsenic uptake by Lemna minor in hydroponic system.

PubMed

Goswami, Chandrima; Majumder, Arunabha; Misra, Amal Kanti; Bandyopadhyay, Kaushik

2014-01-01

Arsenic is hazardous and causes several ill effects on human beings. Phytoremediation is the use of aquatic plants for the removal of toxic pollutants from external media. In the present research work, the removal efficiency as well as the arsenic uptake capacity of duckweed Lemna minor has been studied. Arsenic concentration in water samples and plant biomass were determined by AAS. The relative growth factor of Lemna minor was determined. The duckweed had potential to remove as well as uptake arsenic from the aqueous medium. Maximum removal of more than 70% arsenic was achieved atinitial concentration of 0.5 mg/1 arsenic on 15th day of experimental period of 22 days. Removal percentage was found to decrease with the increase in initial concentration. From BCF value, Lemna minor was found to be a hyperaccumulator of arsenic at initial concentration of 0.5 mg/L, such that accumulation decreased with increase in initial arsenic concentration.

Assessing the Role of Dissolved Organic Phosphate on Rates of Microbial Phosphorus Cycling

NASA Astrophysics Data System (ADS)

Gonzalez, A. C.; Popendorf, K. J.; Duhamel, S.

2016-02-01

Phosphorus (P) is an element crucial to life, and it is limiting in many parts of the ocean. In oligotrophic environments, the dissolved P pool is cycled rapidly through the activity of microbes, with turnover times of several hours or less. The overarching aim of this study was to assess the flux of P from picoplankton to the dissolved pool and the role this plays in fueling rapid P cycling. To determine if specific microbial groups are responsible for significant return of P to the dissolved pool during cell lifetime, we compared the rate of cellular P turnover (cell-Pτ, the rate of cellular P uptake divided by cellular P content) to the rate of cellular biomass turnover (cellτ). High rates of P return to the dissolved pool during cell lifetime (high cell-Pτ/cellτ) indicate significant P regeneration, fueling more rapid turnover of the dissolved P pool. We hypothesized that cell-Pτ/cellτ varies widely across picoplankton groups. One factor influencing this variation may be each microbial group's relative uptake of dissolved organic phosphorus (DOP) versus dissolved inorganic phosphorus (DIP). As extracellular hydrolysis is necessary for P incorporation from DOP, this process may return more P to the dissolved pool than DIP incorporation. This leads to the question: does a picoplankton's relative uptake of DOP (versus DIP) affect the rate at which it returns phosphorus to the dissolved pool? To address this question, we compared the rate of cellular P turnover based on uptake of DOP and uptake DIP using cultured representatives of three environmentally significant picoplankton groups: Prochlorococcus, Synechococcus, and heterotrophic bacteria. These different picoplankton groups are known to take up different ratios of DOP to DIP, and may in turn make significantly different contributions to the regeneration and cycling phosphorus. These findings have implications towards our understanding of the timeframes of biogeochemical cycling of phosphorus in the ocean.

Quadrivalent human papillomavirus vaccine uptake in adolescent boys and maternal utilization of preventive care and history of sexually transmitted infections.

PubMed

Hechter, Rulin C; Chao, Chun; Sy, Lina S; Ackerson, Bradley K; Slezak, Jeff M; Sidell, Margo A; Jacobsen, Steven J

2013-09-01

We examined whether maternal utilization of preventive care and history of sexually transmitted infections (STIs) predicted quadrivalent human papillomavirus vaccine (HPV4) uptake among adolescent boys 1 year following the recommendation for permissive use of HPV4 for males. We linked maternal information with electronic health records of 254 489 boys aged 9 to 17 years who enrolled in Kaiser Permanente Southern California health plan from October 21, 2009, through December 21, 2010. We used multivariable Poisson regression with robust error variance to examine whether HPV4 initiation was associated with maternal uptake of influenza vaccine, Papanicolaou (Pap) screening, and history of STIs. We identified a modest but statistically significant association between initiation of HPV4 series and maternal receipt of influenza vaccine (rate ratio [RR] = 1.16; 95% confidence interval [CI] = 1.07, 1.26) and Pap screening (RR = 1.13; 95% CI = 1.01, 1.26). Boys whose mothers had a history of genital warts were more likely to initiate HPV4 (RR = 1.47; 95% CI = 0.93, 2.34), although the association did not reach statistical significance (P = .1). Maternal utilization of preventive care and history of genital warts may influence HPV4 uptake among adolescent boys. The important role of maternal health characteristics and health behaviors needs be considered in intervention efforts to increase vaccine uptake among boys.

Functional imaging in differentiating bronchial masses: an initial experience with a combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan.

PubMed

Kumar, Arvind; Jindal, Tarun; Dutta, Roman; Kumar, Rakesh

2009-10-01

To evaluate the role of combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in differentiating bronchial tumors observed in contrast enhanced computed tomography scan of chest. Prospective observational study. Place of study: All India Institute of Medical Sciences, New Delhi, India. 7 patients with bronchial mass detected in computed tomography scan of the chest were included in this study. All patients underwent (18)F-FDG PET-CT scan, (68)Ga DOTA-TOC PET-CT scan and fiberoptic bronchoscope guided biopsy followed by definitive surgical excision. The results of functional imaging studies were analyzed and the results are correlated with the final histopathology of the tumor. Histopathological examination of 7 bronchial masses revealed carcinoid tumors (2 typical, 1 atypical), inflammatory myofibroblastic tumor (1), mucoepidermoid carcinoma (1), hamartoma (1), and synovial cell sarcoma (1). The typical carcinoids had mild (18)F-FDG uptake and high (68)Ga DOTA-TOC uptake. Atypical carcinoid had moderate uptake of (18)F-FDG and high (68)Ga DOTA-TOC uptake. Inflammatory myofibroblastic tumor showed high uptake of (18)F-FDG and no uptake of (68)Ga DOTA-TOC. Mucoepidermoid carcinoma showed mild (18)F-FDG uptake and no (68)Ga DOTA-TOC uptake. Hamartoma showed no uptake on either scans. Synovial cell sarcoma showed moderate (18)F-FDG uptake and mild focal (68)Ga DOTA-TOC uptake. This initial experience with the combined use of (18)F-FDG and (68)Ga DOTA-TOC PET-CT scan reveals different uptake patterns in various bronchial tumors. Bronchoscopic biopsy will continue to be the gold standard; however, the interesting observations made in this study merits further evaluation of the utility of the combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in larger number of patients with bronchial masses.

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

PubMed

Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann

2003-12-01

There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.

Coupling of methylmercury uptake with respiration and water pumping in freshwater tilapia Oreochromis niloticus.

PubMed

Wang, Rui; Wong, Ming-Hung; Wang, Wen-Xiong

2011-09-01

The relationships among the uptake of toxic methylmercury (MeHg) and two important fish physiological processes-respiration and water pumping--in the Nile tilapia (Oreochromis niloticus) were explored in the present study. Coupled radiotracer and respirometric techniques were applied to measure simultaneously the uptake rates of MeHg, water, and oxygen under various environmental conditions (temperature, dissolved oxygen level, and water flow). A higher temperature enhanced MeHg influx and the oxygen consumption rate but had no effect on the water uptake, indicating the influence of metabolism on MeHg uptake. The fish showed a high tolerance to hypoxia, and the oxygen consumption rate was not affected until the dissolved oxygen concentration decreased to extremely low levels (below 1 mg/L). The MeHg and water uptake rates increased simultaneously as the dissolved oxygen level decreased, suggesting the coupling of water flux and MeHg uptake. The influence of fish swimming performance on MeHg uptake was also investigated for the first time. Rapidly swimming fish showed significantly higher uptake rates of MeHg, water, and oxygen, confirming the coupling relationships among respiration, water pumping, and metal uptake. Moreover, these results support that MeHg uptake is a rate-limiting process involving energy. Our study demonstrates the importance of physiological processes in understanding mercury bioaccumulation in fluctuating aquatic environments. Copyright © 2011 SETAC.

Formation and Release of Cobalt(II) Sorption and Precipitation Products in Aging Kaolinite-Water Slurries.

PubMed

Thompson; Parks; Brown

2000-02-15

The uptake and release behavior of cobalt(II) was studied over thousands of hours in CO(2)-free aqueous suspensions of kaolinite under three pairs of total cobalt concentration (Co(T)) and near-neutral pH (7.5-7.8) conditions. Dissolved cobalt, aluminum, and silicon concentrations were monitored by ICPMS, and cobalt-containing products were identified by EXAFS spectroscopy. In each uptake experiment, cobalt sorbed to kaolinite as a mixture of surface-adsorbed monomers or polymers and hydrotalcite-like precipitates of the approximate composition Co(x)Al(OH)(2x+2)(A(n-))(1/n), where 2

Chlorovirus-mediated membrane depolarization of Chlorella alters secondary active transport of solutes.

PubMed

Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L

2008-12-01

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake.

Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells.

PubMed

Seppänen, P; Alhonen-Hongisto, L; Jänne, J

1981-05-05

1. Putrescine and spermidine depletion produced by alpha-difluoromethylornithine, an irreversible inhibitor or ornithine decarboxylase (EC 4.1.1.17), resulted in a strikingly enhanced cellular uptake of methylglyoxal bis(guanylhydrazone) in cultured Ehrlich ascites carcinoma cells and human lymphocytic leukemia cells. 2. A prior priming of the cells with difluoromethylornithine followed by a short exposure of the cells to methylglyoxal bis(guanylhydrazone) rapidly established intracellular concentrations of the latter drug approaching 10 mM. 3. The enhanced transport of methylglyoxal bis(guanylhydrazone) into the tumor cells apparently required metabolic energy as the uptake of extracellular drug rapidly ceased and intracellular methylglyoxal bis(guanylhydrazone) was excreted into the medium when the glycolysis of the tumor cells was inhibited by iodoacetate. 4. A sequential treatment of cultured tumor cells with difluoromethylornithine until established polyamine depletion followed by an addition of low concentrations of methylglyoxal bis(guanylhydrazone) produced an antiproliferative action not achieved with either of the drugs alone. 5. A similar treatment schedule, i.e a priming of mice inoculated with Ehrlich ascites cells with difluoromethylornithine for a few days, likewise enhanced the uptake of methylglyoxal bis(guanylhydrazone) by the carcinoma cells, but only marginally increased the drug concentration in the liver and small intestine of the animals.

Chlorovirus-Mediated Membrane Depolarization of Chlorella Alters Secondary Active Transport of Solutes▿

PubMed Central

Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L.

2008-01-01

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake. PMID:18842725

Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation.

PubMed

Goji, Takeo; Takahara, Kazuhiko; Negishi, Manabu; Katoh, Hironori

2017-12-01

Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species. However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation ( i.e. in high glucose dependence), which rapidly induces cell death. However, the precise mechanism of this type of cell death remains unknown. Here, we report that glucose deprivation alone does not trigger glioblastoma cell death. We found that, for cell death to occur in glucose-deprived glioblastoma cells, cystine and glutamine also need to be present in culture media. We observed that cystine uptake through the cystine/glutamate antiporter xCT under glucose deprivation rapidly induces NADPH depletion, reactive oxygen species accumulation, and cell death. We conclude that although cystine uptake is crucial for production of antioxidant glutathione in cancer cells its transport through xCT also induces oxidative stress and cell death in glucose-deprived glioblastoma cells. Combining inhibitors targeting cancer-specific glucose metabolism with cystine and glutamine treatment may offer a therapeutic approach for glioblastoma tumors exhibiting high xCT expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Retrospective analysis of antiretroviral therapy uptake and retention of male clients receiving methadone maintenance therapy in two provinces in Vietnam: potential synergy of the two therapies.

PubMed

Pham, Linh Thi Thuy; Kitamura, Akiko; Do, Hoa Mai; Lai, Kim Anh; Le, Nhan Tuan; Nguyen, Van Thi Thuy; Kato, Masaya

2017-02-17

Vietnam has a concentrated HIV epidemic with injection drug use being the dominant mode of HIV transmission. Vietnam has rapidly expanded antiretroviral therapy (ART) and methadone maintenance therapy (MMT). This study aims to analyze ART uptake and retention among male clients receiving MMT in Vietnam in the early phase of the MMT program. The male clients (age ≥18) who were newly enrolled in care or started ART at two HIV clinics in Hanoi (2009 to 2011) and three HIV clinics in Can Tho (2010 to 2012) were included for the analysis. The CD4 lymphocyte count at HIV care enrollment and ART initiation and retention on ART were retrospectively analyzed. The values of those receiving MMT were compared with the values of two groups: those in whom injection drug use (IDU) status was documented, but were not receiving MMT, and all male clients not receiving MMT. To analyze retention, survival analysis with log rank test and Cox proportional hazard model was used. During the study period, 663 adult men were newly enrolled in HIV care (237 had IDU status documented) and 456 initiated ART (167 had IDU status documented). Among those who initiated ART, 28 were receiving MMT. At care enrolment, those receiving MMT had a median CD4 count of 230 (IQR 57-308) cells/mm 3 , while men self-reporting IDU and not receiving MMT and all men not receiving MMT had a median CD4 count of 158 (IQR 50-370) cells/mm 3 and 143 (IQR 35-366) cells/mm 3 , respectively. At ART initiation, men receiving MMT had significantly higher CD4 count with median at 203 (IQR 64-290) cells/mm 3 than men self-reporting IDU and not receiving MMT (80, IQR 40-220, cells/mm 3 , p = 0.038) and all men not receiving MMT (76, IQR 20-199, cells/mm 3 , p = 0.009). Those receiving MMT had a significantly higher retention rate than those self-reporting IDU but not receiving MMT (hazard ratio = 0.18, p = 0.019) and men not receiving MMT (hazard ratio = 0.20, p = 0.041). Our analysis suggests that men receiving MMT in Vietnam are achieving relatively early uptake and high retention rates on ART. The findings support potential benefits of integrating MMT and ART services in Vietnam.

Transport by the lactose permease of Escherichia coli as the basis of lactose killing.

PubMed Central

Dykhuizen, D; Hartl, D

1978-01-01

Lactose killing is a peculiar phenomenon in which 80 to 98% of the Escherichia coli cells taken from a lactose-limited chemostat die when plated on standard lactose minimal media. This unique form of suicide is caused by the action of the lactose permease. Since uptake of either lactose or galactose by the lactose permease caused death, the action of rapid transport across the membrane must be the cause of the phenomenon. Alternative causes of lactose killing, such as accumulation of toxic metabolic intermediates or action of the beta-galactosidase, have been eliminated. It is proposed that rapid uptake of sugars by the lactose permease disrupts membrane function, perhaps causing collapse of the membrane potential. PMID:99437

Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy.

PubMed

Nikolaidis, Lazaros A; Elahi, Dariush; Hentosz, Teresa; Doverspike, Aaron; Huerbin, Rhonda; Zourelias, Lee; Stolarski, Carol; Shen, You-tang; Shannon, Richard P

2004-08-24

The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake. Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol x kg(-1) x min(-1)). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant (P<0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group. rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.

Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688.

PubMed

Ametamey, Simon M; Treyer, Valerie; Streffer, Johannes; Wyss, Matthias T; Schmidt, Mark; Blagoev, Milen; Hintermann, Samuel; Auberson, Yves; Gasparini, Fabrizio; Fischer, Uta C; Buck, Alfred

2007-02-01

3-(6-Methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime (11C-ABP688), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET agent. Six healthy male volunteers (mean age, 25 y; range, 21-33 y) were studied. Brain perfusion (15O-H2O) was measured immediately before each 11C-ABP688 PET scan. For anatomic coregistration, T1-weighted MRI was performed on each subject. Arterial blood samples for the determination of the arterial input curve were obtained at predefined time points, and 11C-ABP688 uptake was assessed quantitatively using a 2-tissue-compartment model. An initial rapid uptake of radioactivity followed by a gradual clearance from all examined brain regions was observed. Relatively high radioactivity concentrations were observed in mGluR5-rich brain regions such as the anterior cingulate, medial temporal lobe, amygdala, caudate, and putamen, whereas radioactivity uptake in the cerebellum and white matter, regions known to contain low densities of mGluR5, was low. Specific distribution volume as an outcome measure of mGluR5 density in the various brain regions ranged from 5.45 +/- 1.47 (anterior cingulate) to 1.91 +/- 0.32 (cerebellum), and the rank order of the corresponding specific distribution volumes of 11C-ABP688 in cortical regions was temporal > frontal > occipital > parietal. The metabolism of 11C-ABP688 in plasma was rapid; at 60 min after injection, 25% +/- 0.03% of radioactivity measured in the plasma of healthy volunteers was intact parent compound. The results of these studies indicate that 11C-ABP688 has suitable characteristics and is a promising PET ligand for imaging mGluR5 distribution in humans. Furthermore, it could be of great value for the selection of appropriate doses of clinically relevant candidate drugs that bind to mGluR5 and for PET studies of patients with psychiatric and neurologic disorders.

Climate-related changes of soil characteristics affect bacterial community composition and function of high altitude and latitude lakes.

PubMed

Rofner, Carina; Peter, Hannes; Catalán, Núria; Drewes, Fabian; Sommaruga, Ruben; Pérez, María Teresa

2017-06-01

Lakes at high altitude and latitude are typically unproductive ecosystems where external factors outweigh the relative importance of in-lake processes, making them ideal sentinels of climate change. Climate change is inducing upward vegetation shifts at high altitude and latitude regions that translate into changes in the pools of soil organic matter. Upon mobilization, this allochthonous organic matter may rapidly alter the composition and function of lake bacterial communities. Here, we experimentally simulate this potential climate-change effect by exposing bacterioplankton of two lakes located above the treeline, one in the Alps and one in the subarctic region, to soil organic matter from below and above the treeline. Changes in bacterial community composition, diversity and function were followed for 72 h. In the subarctic lake, soil organic matter from below the treeline reduced bulk and taxon-specific phosphorus uptake, indicating that bacterial phosphorus limitation was alleviated compared to organic matter from above the treeline. These effects were less pronounced in the alpine lake, suggesting that soil properties (phosphorus and dissolved organic carbon availability) and water temperature further shaped the magnitude of response. The rapid bacterial succession observed in both lakes indicates that certain taxa directly benefited from soil sources. Accordingly, the substrate uptake profiles of initially rare bacteria (copiotrophs) indicated that they are one of the main actors cycling soil-derived carbon and phosphorus. Our work suggests that climate-induced changes in soil characteristics affect bacterioplankton community structure and function, and in turn, the cycling of carbon and phosphorus in high altitude and latitude aquatic ecosystems. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Astroglial Glutamate Signaling and Uptake in the Hippocampus

PubMed Central

Rose, Christine R.; Felix, Lisa; Zeug, Andre; Dietrich, Dirk; Reiner, Andreas; Henneberger, Christian

2018-01-01

Astrocytes have long been regarded as essentially unexcitable cells that do not contribute to active signaling and information processing in the brain. Contrary to this classical view, it is now firmly established that astrocytes can specifically respond to glutamate released from neurons. Astrocyte glutamate signaling is initiated upon binding of glutamate to ionotropic and/or metabotropic receptors, which can result in calcium signaling, a major form of glial excitability. Release of so-called gliotransmitters like glutamate, ATP and D-serine from astrocytes in response to activation of glutamate receptors has been demonstrated to modulate various aspects of neuronal function in the hippocampus. In addition to receptors, glutamate binds to high-affinity, sodium-dependent transporters, which results in rapid buffering of synaptically-released glutamate, followed by its removal from the synaptic cleft through uptake into astrocytes. The degree to which astrocytes modulate and control extracellular glutamate levels through glutamate transporters depends on their expression levels and on the ionic driving forces that decrease with ongoing activity. Another major determinant of astrocytic control of glutamate levels could be the precise morphological arrangement of fine perisynaptic processes close to synapses, defining the diffusional distance for glutamate, and the spatial proximity of transporters in relation to the synaptic cleft. In this review, we will present an overview of the mechanisms and physiological role of glutamate-induced ion signaling in astrocytes in the hippocampus as mediated by receptors and transporters. Moreover, we will discuss the relevance of astroglial glutamate uptake for extracellular glutamate homeostasis, focusing on how activity-induced dynamic changes of perisynaptic processes could shape synaptic transmission at glutamatergic synapses. PMID:29386994

Azadirachtin: an effective systemic insecticide for control of Agrilus planipennis (Coleoptera: Buprestidae).

PubMed

McKenzie, Nicole; Helson, Blair; Thompson, Dean; Otis, Gard; McFarlane, John; Buscarini, Teresa; Meating, Joe

2010-06-01

The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), an invasive pest discovered in North America in 2002, is now well established and threatens ash (Fraxinus spp.) trees throughout the continent. Experiments were conducted to 1) examine the efficacy of an alternative natural pesticide, azadirachtin, to control emerald ash borer, and 2) determine foliar uptake and dissipation patterns after systemic injections of azadirachtin into trunks of small (2.2 cm diameter at breast height [dbh]), uninfested green ash trees. We found no evidence of mortality of adult beetles. In contrast, fewer larvae completed their development at dose levels > or = 1.7 mg (AI)/cm dbh and development ceased beyond the second instar at dose levels > or = 13.6 mg (AI)/cm dbh. Substantial concentrations (11.2 microg/g dry mass [SD = 7.55]) of azadirachtin were present in leaves within 7 d of treatment. After rapid initial uptake, concentrations in leaves declined logarithmically during the 55 d after injection. A similar pattern was observed in a separate experiment that examined the uptake and translocation of azadirachtin in larger green ash trees (22 cm dbh) treated with 250 mg (AI) /cm dbh with the EcoJect injection system. In another experiment, recently infested plantation green ash trees treated with doses > or = 40 mg (AI)/cm dbh had significant reductions in adult emergence approximately 1 yr postinjection. Given the inhibition of larval development, reduction of adult emergence, and the occurrence of foliar residues at biologically active concentrations, we conclude that azadirachtin is effective in protecting ash trees from emerald ash borer.

Reasons for non-uptake and subsequent participation in the NHS Bowel Cancer Screening Programme: a qualitative study.

PubMed

Palmer, C K; Thomas, M C; von Wagner, C; Raine, R

2014-04-02

Screening for bowel cancer using the guaiac faecal occult blood test offered by the NHS Bowel Cancer Screening Programme (BCSP) is taken up by 54% of the eligible population. Uptake ranges from 35% in the most to 61% in the least deprived areas. This study explores reasons for non-uptake of bowel cancer screening, and examines reasons for subsequent uptake among participants who had initially not taken part in screening. Focus groups with a socio-economically diverse sample of participants were used to explore participants' experience of invitation to and non-uptake of bowel cancer screening. Participants described sampling faeces and storing faecal samples as broaching a cultural taboo, and causing shame. Completion of the test kit within the home rather than a formal health setting was considered unsettling and reduced perceived importance. Not knowing screening results was reported to be preferable to the implications of a positive screening result. Feeling well was associated with low perceived relevance of screening. Talking about bowel cancer screening with family and peers emerged as the key to subsequent participation in screening. Initiatives to normalise discussion about bowel cancer screening, to link the BCSP to general practice, and to simplify the test itself may lead to increased uptake across all social groups.

SU-E-I-14: Comparison of Iodine-Labeled and Indium-Labeled Antibody Biodistributions

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

Williams, L

2014-06-01

Purpose: It is often assumed that animal biodistributions of novel proteins are not dependent upon the radiolabel used in their determination. In units of percent injected dose per gram of tissue (%ID/g), organ uptake results (u) may be obtained using either iodine or metal as radioactive labels. Iodination is preferred as it is a one-step process whereas metal labeling requires two chemical procedures and therefore more protein material. It is important to test whether the radioactive tag leads to variation in the uptake value. Methods: Uptakes of 3antibodies to Carcinoembryonic Antigen (CEA) were evaluated in a nude mouse model bearingmore » 150 to 300 mg LS174T human colon cancer xenografts. Antibodies included diabody (56 kDa), minibody (80kDa) and intact M5A (150 kDa) anti-CEA cognates. Both radioiodine and indium-111 labels were used with uptakes evaluated at 7 time(t) points out to 96 h. Ratios (R) of u(iodine-label)/u(indium-label) were determined for liver, spleen, kidneys, lung and tumor. Results: Hepatic loss was rapid for diabody and minibody; by 24 h their R values were only 2%; i.e., uptake of iodine was 2% of that of indium for these 2 antibodies. By contrast, R for the intact cognate was 50% at that time point. Splenic results were similar. Tumor uptake ratios did not depend upon the antibody type and were 50% at 24 h. Conclusions: Relatively rapid loss of iodine relative to indium in liver and spleen was observed in lower mass antibodies. Tumor ratios were larger and independent of antibody type. Aside from tumor, the R ratio of uptakes depended on the antibody type. R values decreased monotonically with time in all tissues and for all cognates. Using this ratio, one can possibly correct iodine-based u (t) results so that they resemble radiometal-derived biodistributions.« less

Effect of Thiols, Zinc, and Redox Conditions on Hg Uptake in Shewanella oneidensis

DOE PAGES

Szczuka, Aleksandra; Morel, Francois M. M.; Schaefer, Jeffra K.

2015-05-18

Mercury uptake in bacteria represents a key first step in the production and accumulation Of methylmercury in biota. Previous experiments with mercury methylating bacteria have shown that Hg uptake is enhanced by some thiols, in particular cysteine, and that it is an energy-dependent process through heavy Metal TA transporters. In this study, we examine Hg uptake in the nonmethylating facultative aerobe, Shewanella oneidensis, under both anaerobic and aerobic conditions. Our results demonstrate similar characteristics of the Hg uptake system to those of the Hg methylating strains: uptake is enhanced in the presence of some thiols but not others; uptake ismore » energy dependent as evidenced by inhibition by a protonophore; and uptake is inhibited by high Zn(II) concentrations. Initial cellular uptake rates in S. oneidensis were remarkably similar under aerobic and fumarate-reducing conditions. In conclusion, these data support a similar Hg(II) uptake mechanism within the proteobacteria of accidental Hg(II) transport through heavy metal transporters with similar rates of uptake but differences in the ability to take up Hg bound to different thiols.« less

Adenosine uptake by the isolated epithelium of guine pig jejunum.

PubMed

Kolassa, N; Stengg, R; Turnheim, K

1977-10-01

The uptake of [8-14C]adenosine by the isolated epithelium of guinea pig jejunum was faster than that of inosine, hypoxanthine, or adenine. The initial velocity of adenosine uptake from both the luminal and the antiluminal side of the epithelium exhibited saturation kinetics. The apparent Km, V, and passive permeability of luminal adenosine uptake were all lower than the corresponding values of antiluminal uptake. p-Nitrobenzyl-thioguanosine inhibited adenosine uptake from both the luminal and the antiluminal side, whilst hexobendine decreased the uptake only from the antiluminal side of the epithelium. The results suggest that adenosine enters the intestinal epithelium by a carrier-mediated process in addition to passive diffusion. The antiluminal transport system for adenosine seems similar to that of other tissues with respect to hexobendine inhibition; the luminal transport mechanism, however, exhibits different properties, being insensitive to hexobendine.

Heart testing compound

DOEpatents

Knapp, Jr., Furn F.; Goodman, Mark M.

1985-01-01

The compound 15-(p-[.sup.125 I]-iodophenyl)-6-tellurapentadecanoic acid is disclosed as a myocardial imaging agent having rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination.

Heart testing compound

DOEpatents

Knapp, F.F. Jr.; Goodman, M.M.

1983-06-29

The compound 15-(p-(/sup 125/I)-iodophenyl)-6-tellurapentadecanoic acid is disclosed as a myocardial imaging agent having rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination.

How internal drainage affects evaporation dynamics from soil surfaces ?

NASA Astrophysics Data System (ADS)

Or, D.; Lehmann, P.; Sommer, M.

2017-12-01

Following rainfall, infiltrated water may be redistributed internally to larger depths or lost to the atmosphere by evaporation (and by plant uptake from depths at longer time scales). A large fraction of evaporative losses from terrestrial surfaces occurs during stage1 evaporation during which phase change occurs at the wet surface supplied by capillary flow from the soil. Recent studies have shown existence of a soil-dependent characteristic length below which capillary continuity is disrupted and a drastic shift to slower stage 2 evaporation ensues. Internal drainage hastens this transition and affect evaporative losses. To predict the transition to stage 2 and associated evaporative losses, we developed an analytical solution for evaporation dynamics with concurrent internal drainage. Expectedly, evaporative losses are suppressed when drainage is considered to different degrees depending on soil type and wetness. We observe that high initial water content supports rapid drainage and thus promotes the sheltering of soil water below the evaporation depth. The solution and laboratory experiments confirm nonlinear relationship between initial water content and total evaporative losses. The concept contributes to establishing bounds on regional surface evaporation considering rainfall characteristics and soil types.

Development and characterization of surface engineered PPI dendrimers for targeted drug delivery.

PubMed

Kaur, Avleen; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N K

2017-05-01

In this study, we reported folate-conjugated polypropylene imine dendrimers (FA-PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX-FA-PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX-FA-PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation.

Quadrivalent Human Papillomavirus Vaccine Uptake in Adolescent Boys and Maternal Utilization of Preventive Care and History of Sexually Transmitted Infections

PubMed Central

Chao, Chun; Sy, Lina S.; Ackerson, Bradley K.; Slezak, Jeff M.; Sidell, Margo A.; Jacobsen, Steven J.

2013-01-01

Objectives. We examined whether maternal utilization of preventive care and history of sexually transmitted infections (STIs) predicted quadrivalent human papillomavirus vaccine (HPV4) uptake among adolescent boys 1 year following the recommendation for permissive use of HPV4 for males. Methods. We linked maternal information with electronic health records of 254 489 boys aged 9 to 17 years who enrolled in Kaiser Permanente Southern California health plan from October 21, 2009, through December 21, 2010. We used multivariable Poisson regression with robust error variance to examine whether HPV4 initiation was associated with maternal uptake of influenza vaccine, Papanicolaou (Pap) screening, and history of STIs. Results. We identified a modest but statistically significant association between initiation of HPV4 series and maternal receipt of influenza vaccine (rate ratio [RR] = 1.16; 95% confidence interval [CI] = 1.07, 1.26) and Pap screening (RR = 1.13; 95% CI = 1.01, 1.26). Boys whose mothers had a history of genital warts were more likely to initiate HPV4 (RR = 1.47; 95% CI = 0.93, 2.34), although the association did not reach statistical significance (P = .1). Conclusions. Maternal utilization of preventive care and history of genital warts may influence HPV4 uptake among adolescent boys. The important role of maternal health characteristics and health behaviors needs be considered in intervention efforts to increase vaccine uptake among boys. PMID:23865707

Bacteria foraging in turbulent waters

NASA Astrophysics Data System (ADS)

Taylor, John; Tang, Wenbo; Stocker, Roman

2009-11-01

Marine bacteria are the Ocean's recyclers, contributing to as much as 50% of the productivity of the marine food web. Bacteria forage on patches of dissolved nutrients using chemotaxis, the ability to swim up chemical gradients. As turbulence is ubiquitous in the Ocean, it is important to understand how turbulent flow conditions affect bacterial foraging. We used three-dimensional, isotropic direct numerical simulations coupled with a bacterial transport equation to address this problem. After the flow is continuously forced until it reaches a steady state, microscale nutrient patches are injected into the turbulent flow, and stirring produces thin nutrient filaments. Two populations of bacteria compete against each other: one population is motile and chemotactic (`active'), the other is non-motile (`passive'). The distribution of both populations is initially uniform. Chemotaxis allows active bacteria to cluster near the center of the nutrient filaments, increasing their nutrient uptake relative to passive bacteria. Increasing the turbulence intensity increases the short-term chemotactic advantage by quickly producing large gradients in the nutrient concentration, but also leads to rapid mixing of the nutrient field, which makes the chemotactic advantage short-lived. The results suggest that the evolutionary advantage of chemotaxis, based on the increase in nutrient uptake relative to the energetic cost of swimming, strongly depends on the turbulence level.

Uptake and intracellular fate of [14C]sucrose-insulin in perfused rat livers.

PubMed

Surmacz, C A; Wert, J J; Ward, W F; Mortimore, G E

1988-07-01

Insulin was covalently linked to [14C]sucrose by means of cyanuric chloride to provide a label that would remain entrapped within the vacuolar system. The uptake of the conjugate by the perfused rat liver was rapid (half-life = 2.9 min), competitively inhibited by native insulin, and abolished by alkali denaturation. As assessed by its distribution on self-generating gradients of colloidal silica-povidone, label in lysosome-enriched samples of liver taken at different times after the addition of the conjugate moved progressively during 15 min from the plasma membrane into an intermediate peak and then to dense lysosomal fractions. After 30-60 min, the label had equilibrated throughout the lysosomal-vacuolar system. The initial movement from the plasma membrane to the intermediate peak occurred between 2 and 5 min. Because label in the peak could be physically separated from the lysosomal marker, beta-acetylglucosaminidase, by dispersing the sample through the gradient mixture before centrifugation rather than layering it, we concluded that the intermediate particles in question were not lysosomal in nature. On gel-filtration chromatography, label extracted from the intermediate peak did not move with insulin but rather as a broad band of lower molecular weight products, suggesting that insulin is subject to early proteolytic attack within a nonlysosomal compartment.

Surface engineered dendrimers as antiangiogenic agent and carrier for anticancer drug: dual attack on cancer.

PubMed

Jain, K; Jain, N K

2014-07-01

The present research work describes the formulation of arginine conjugated 3.0G Poly(propylene) imine (PPI) dendrimers, mimicking the surface structure of an endogenous angiogenesis-inhibitor endostatin; for tumor specific delivery of a model anticancer drug, doxorubicin hydrochloride (Dox). Synthesis of PPI dendrimers and conjugation of arginine to surface groups was confirmed by FTIR, NMR, TEM and mass spectrometry. Drug was loaded by equilibrium dialysis method and developed formulation was evaluated for entrapment efficiency, hemolytic toxicity, in vitro drug release, stability, anti-angiogenic activity via in vivo chick embryo chorioallantoic membrane (CAM) assay, and anticancer activity and cell uptake using MCF-7 cancer cell lines. The system exhibited the initial rapid release followed by sustained release of Dox with significant antiangiogenic activity in the CAM assay. Further, the arginine conjugated dendrimers was found to inhibit growth of cancer cells in ex vivo studies with MCF-7 cell lines. Cell uptake studies suggested that in comparison to free drug the formulation was preferably taken up by the tumor cells. Thus the two pronged attack on cancerous tissue i.e., inhibition of angiogenesis and killing of cancer cells by anticancer drug, might prove to be a promising approach in the treatment of fatal disease, cancer.

Kinetic studies on phosphorus sorption by selected soil amendments for septic tank effluent renovation.

PubMed

Cheung, K C; Venkitachalam, T H

2006-01-01

A systematic kinetic study of phosphorus (P) sorption by various materials in the soil infiltration system of septic tanks was undertaken by following the time course of P sorption by sorbents in contact with various P solutions over periods up to 360 days. Uptake of P seemed to consist of two distinct stages. Initial uptake was very rapid and this phase was completed in 4 days or less. A slower removal stage followed for some materials over many months. Phosphorus sorption during the fast reaction stage appeared to be associated with the soluble Ca content of the materials. The fast reaction of calcareous materials accounted for the bulk (>70%) of the total P removed. Merribrook loamy sand exhibited the highest proportion of P sorption during the slow phase. It should be noted, however, that for solution P concentrations in the range found in typical effluents (approximately 20 mg L(-1)) the fast reaction phase seemed to be responsible for virtually all P removed. None of the six kinetic formulae examined possessed the sophistication and detail needed to portray accurately the time course of P sorption for all the sorbents investigated. The Elovich equation and the kinetic modification of the Freundlich isotherm expression appeared to provide a reasonable fit of the experimental data.

Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species Production in Nickel Hyperaccumulator Alyssum murale*

PubMed Central

Agrawal, Bhavana; Czymmek, Kirk J.; Sparks, Donald L.; Bais, Harsh P.

2013-01-01

Mitochondria are important targets of metal toxicity and are also vital for maintaining metal homeostasis. Here, we examined the potential role of mitochondria in homeostasis of nickel in the roots of nickel hyperaccumulator plant Alyssum murale. We evaluated the biochemical basis of nickel tolerance by comparing the role of mitochondria in closely related nickel hyperaccumulator A. murale and non-accumulator Alyssum montanum. Evidence is presented for the rapid and transient influx of nickel in root mitochondria of nickel hyperaccumulator A. murale. In an early response to nickel treatment, substantial nickel influx was observed in mitochondria prior to sequestration in vacuoles in the roots of hyperaccumulator A. murale compared with non-accumulator A. montanum. In addition, the mitochondrial Krebs cycle was modulated to increase synthesis of malic acid and citric acid involvement in nickel hyperaccumulation. Furthermore, malic acid, which is reported to form a complex with nickel in hyperaccumulators, was also found to reduce the reactive oxygen species generation induced by nickel. We propose that the interaction of nickel with mitochondria is imperative in the early steps of nickel uptake in nickel hyperaccumulator plants. Initial uptake of nickel in roots results in biochemical responses in the root mitochondria indicating its vital role in homeostasis of nickel ions in hyperaccumulation. PMID:23322782

Transient Influx of nickel in root mitochondria modulates organic acid and reactive oxygen species production in nickel hyperaccumulator Alyssum murale.

PubMed

Agrawal, Bhavana; Czymmek, Kirk J; Sparks, Donald L; Bais, Harsh P

2013-03-08

Mitochondria are important targets of metal toxicity and are also vital for maintaining metal homeostasis. Here, we examined the potential role of mitochondria in homeostasis of nickel in the roots of nickel hyperaccumulator plant Alyssum murale. We evaluated the biochemical basis of nickel tolerance by comparing the role of mitochondria in closely related nickel hyperaccumulator A. murale and non-accumulator Alyssum montanum. Evidence is presented for the rapid and transient influx of nickel in root mitochondria of nickel hyperaccumulator A. murale. In an early response to nickel treatment, substantial nickel influx was observed in mitochondria prior to sequestration in vacuoles in the roots of hyperaccumulator A. murale compared with non-accumulator A. montanum. In addition, the mitochondrial Krebs cycle was modulated to increase synthesis of malic acid and citric acid involvement in nickel hyperaccumulation. Furthermore, malic acid, which is reported to form a complex with nickel in hyperaccumulators, was also found to reduce the reactive oxygen species generation induced by nickel. We propose that the interaction of nickel with mitochondria is imperative in the early steps of nickel uptake in nickel hyperaccumulator plants. Initial uptake of nickel in roots results in biochemical responses in the root mitochondria indicating its vital role in homeostasis of nickel ions in hyperaccumulation.

Differential pH-dependent cellular uptake pathways among foamy viruses elucidated using dual-colored fluorescent particles

PubMed Central

2012-01-01

Background It is thought that foamy viruses (FVs) enter host cells via endocytosis because all FV glycoproteins examined display pH-dependent fusion activities. Only the prototype FV (PFV) glycoprotein has also significant fusion activity at neutral pH, suggesting that its uptake mechanism may deviate from other FVs. To gain new insights into the uptake processes of FV in individual live host cells, we developed fluorescently labeled infectious FVs. Results N-terminal tagging of the FV envelope leader peptide domain with a fluorescent protein resulted in efficient incorporation of the fluorescently labeled glycoprotein into secreted virions without interfering with their infectivity. Double-tagged viruses consisting of an eGFP-tagged PFV capsid (Gag-eGFP) and mCherry-tagged Env (Ch-Env) from either PFV or macaque simian FV (SFVmac) were observed during early stages of the infection pathway. PFV Env, but not SFVmac Env, containing particles induced strong syncytia formation on target cells. Both virus types showed trafficking of double-tagged virions towards the cell center. Upon fusion and subsequent capsid release into the cytosol, accumulation of naked capsid proteins was observed within four hours in the perinuclear region, presumably representing the centrosomes. Interestingly, virions harboring fusion-defective glycoproteins still promoted virus attachment and uptake, but failed to show syncytia formation and perinuclear capsid accumulation. Biochemical and initial imaging analysis indicated that productive fusion events occur predominantly within 4–6 h after virus attachment. Non-fused or non-fusogenic viruses are rapidly cleared from the cells by putative lysosomal degradation. Quantitative monitoring of the fraction of individual viruses containing both Env and capsid signals as a function of time demonstrated that PFV virions fused within the first few minutes, whereas fusion of SFVmac virions was less pronounced and observed over the entire 90 minutes measured. Conclusions The characterized double-labeled FVs described here provide new mechanistic insights into FV early entry steps, demonstrating that productive viral fusion occurs early after target cell attachment and uptake. The analysis highlights apparent differences in the uptake pathways of individual FV species. Furthermore, the infectious double-labeled FVs promise to provide important tools for future detailed analyses on individual FV fusion events in real time using advanced imaging techniques. PMID:22935135

Papaya Seeds as A Low-Cost Sorbent for Removing Cr(VI) from The Aqueous Solution

NASA Astrophysics Data System (ADS)

Rahmawati, Atik; Marwoto, Putut; Karunia Z, Anita

2016-08-01

The presence of chromium (VI) contaminants and their toxicity in aqueous streams important environmental problems. Adsorption is one of the effective techniques that can be used for removing metal from wastewater. This research was initiated by preparing sorbent from papaya seeds and determining its functional group contents by using FT-IR. The adsorption process was carried out in a batch method. The study of adsorption aspects involved the pH, initial Cr (VI) concentration and contact time between Cr (VI) and sorbent. FT IR analysis results showed that the main functional groups are carbonyl, hydroxyl, and carboxylic. It was also found that the effective pH for Cr (VI) uptake is 2.0 and increasing contact time would increase the Cr (VI) uptake. In addition, the equilibrium was reached after 40 minutes interaction and the increase of initial chromium (VI) concentration would increase the sorbent uptake percentage. All these results indicated that papaya seed is a potential sorbent for removing Cr (VI) from aqueous solutions.

Implementing a continuum of evidence-based psychosocial interventions for people with severe mental illness: part 1-review of major initiatives and implementation strategies.

PubMed

Menear, Matthew; Briand, Catherine

2014-04-01

Providing comprehensive care to people with severe mental illness (SMI) involves moving beyond pharmacological treatment and ensuring access to a wide range of evidence-based psychosocial services. Numerous initiatives carried out in North America and internationally have promoted the widespread adoption of such services. Objectives of this rapid review were 3-fold: to identify these implementation initiatives, to describe the implementation strategies used to promote the uptake of psychosocial services, and to identify key issues related to the implementation of a broad range of services. Part 1 presents findings for objectives 1 and 2 of the review. Searches were carried out in MEDLINE and PsycINFO for reports published between 1990 and 2012 using key words related to SMI, psychosocial practices, and implementation. Contacts with experts and reference list and reverse citation searches were also conducted. Fifty-five articles were retained that identified more than a dozen major North American and international implementation initiatives. Initiative leaders employed diverse strategies at the planning, execution, and evaluation stages of the implementation process. Stakeholder meetings, training, ongoing consultation, and quality or fidelity monitoring were strategies consistently adopted across most initiatives, whereas theory-based approaches and organizational- and system-level strategies were less frequently described. Insights from the initiatives identified in this review can help guide future efforts to implement a broad range of psychosocial services for people with SMI. However, such efforts will also need to be informed by more rigorous, theory-based studies of implementation processes and outcomes.

Increase in left liver lobe function after preoperative right portal vein embolisation assessed with gadolinium-EOB-DTPA MRI.

PubMed

Geisel, Dominik; Lüdemann, Lutz; Keuchel, Thomas; Malinowski, Maciej; Seehofer, Daniel; Stockmann, Martin; Hamm, Bernd; Gebauer, Bernhard; Denecke, Timm

2013-09-01

To prospectively evaluate the early development of regional liver function after right portal vein embolisation (PVE) with Gd-EOB-DTPA-enhanced MRI in patients scheduled for extended right hemihepatectomy. Ten patients who received a PVE before an extended hemihepatectomy were examined before and 14 days after PVE using Gd-EOB-DTPA-enhanced MRI of the liver. In these sequences representative region of interest measurements were performed in the embolised right (RLL) and the non-embolised left liver lobe (LLL). The volume as well as hepatic uptake index (HUI) was calculated independently for each lobe. Relative enhancement 14 days after PVE decreased in the RLL and increased significantly in the LLL (P < 0.05). Average hepatic uptake index (HUI) for RLL was significantly lower 14 days after PVE than before PVE (P < 0.05) and significantly higher for LLL (P < 0.05). A significant shift of contrast uptake from the right to the left liver lobe can be depicted as early as 14 days after right PVE by using Gd-EOB-DTPA-enhanced MRI, which could reflect the redirected portal venous blood flow and the rapid utilisation of a hepatic functional reserve. • Preoperative portal vein embolisation (PVE) is widely performed before right-sided hepatic resection. • PVE increases intravenous contrast medium uptake in the left lobe of liver. • The hepatic uptake index for the left liver lobe increases rapidly after PVE. • Left liver lobe function increase may be visualised by Gd-EOB-DTPA-enhanced MRI.

Onset of vitellogenin production and vitellogenesis, and their relationship to changes in the midgut epithelium and oocytes in the tick Dermacentor variabilis.

PubMed

Coons, L B; Lamoreaux, W J; Rosell-Davis, R; Tarnowski, B I

1989-05-01

In Dermacentor variabilis (Say), the onset of vitellogenin production and vitellogenesis (uptake of vitellogenin into oocytes) began during the rapid-engorgement feeding period. Mating was required for both vitellogenin production and vitellogenesis to complete the tick's life cycle. Complete immunological identity, as measured by Ouchterlony's double diffusion test, existed between vitellogenin from the fat body, midgut and hemolymph, and vitellin from the ovaries and eggs. Antivitellin antibody did not react with host hemoglobin nor with fat body, midgut, and ovary extracts from feeding females prior to rapid engorgement, feeding unmated females, or unfed or fed males. Some unmated females fed for 13 days and then hand-detached from the host eventually began oviposition after going through a preoviposition period. In these ticks, organ extracts from the midgut, fat body and ovary reacted with antivitellin antibody. The presence or absence of presumed vitellogenic cells in the midgut and yolk bodies in oocytes corresponded with the presence or absence of vitellogenin and vitellogenesis as measured by Ouchterlony's test. Presumed vitellogenic cells increased in size during the preoviposition period. These cells reached their greatest size during the time when the most eggs were being produced, and then declined in size toward the end of oviposition. Vitellogenin was deposited directly into developing yolk bodies in oocytes and was not processed through lysosomes. Feeding was the process that initiated the formation of eggshell cuticle. Detachment from the host was required for the initiation of oviposition.

Overcoming barriers to HPV vaccination: A randomized clinical trial of a culturally-tailored, media intervention among African American girls.

PubMed

DiClemente, Ralph J; Murray, Colleen Crittenden; Graham, Tracie; Still, Julia

2015-01-01

Although genital HPV is the most prevalent STI in the US, rates of vaccination uptake among high-risk subgroups remain low. Investigations of vaccine compliance have mainly targeted mother-daughter dyads, which in some settings may prove difficult. This study examines an innovative culturally tailored, computer-delivered media-based strategy to promote HPV vaccine uptake. Data, inclusive of sociodemographics, sexual behaviors, knowledge, attitudes, and beliefs about HPV and vaccination were collected via ACASI from 216 African American adolescent females (ages 14-18 years) seeking services in family planning and STI public health clinics in metropolitan Atlanta. Data were obtained prior to randomization and participation in an interactive media-based intervention designed to increase HPV vaccination uptake. Medical record abstraction was conducted 7 month post-randomization to assess initial vaccine uptake and compliance. Participants in the intervention were more compliant to vaccination relative to a placebo comparison condition (26 doses vs. Seventeen doses; p=0.12). However, vaccination series initiation and completion were lower than the national average. Thorough evaluation is needed to better understand factors facilitating HPV vaccine uptake and compliance, particularly perceived susceptibility and the influence of the patient-provider encounter in a clinical setting.

A PET Tracer for Renal Organic Cation Transporters, ¹¹C-Metformin: Radiosynthesis and Preclinical Proof-of-Concept Studies.

PubMed

Jakobsen, Steen; Busk, Morten; Jensen, Jonas Brorson; Munk, Ole Lajord; Zois, Nora Elisabeth; Alstrup, Aage K O; Jessen, Niels; Frøkiær, Jørgen

2016-04-01

Organic cation transporters (OCTs) in the kidney proximal tubule (PT) participate in renal excretion of drugs and endogenous compounds. PT function is commonly impaired in kidney diseases, and consequently quantitative measurement of OCT function may provide an important estimate of kidney function. Metformin is a widely used drug and targets OCT type 2 located in the PT. Thus, we hypothesized that (11)C-labeled metformin would be a suitable PET tracer for quantification of renal function. (11)C-metformin was prepared by (11)C-methylation of 1-methylbiguanide. In vitro cell uptake of (11)C-metformin was studied in LLC-PK1 cells in the presence of increasing doses of unlabeled metformin. In vivo small-animal PET studies in Sprague-Dawley rats were performed at baseline and after treatment with OCT inhibitors to evaluate renal uptake of (11)C-metformin. Kidney and liver pharmacokinetics of (11)C-metformin was investigated in vivo by dynamic (11)C-metformin PET/CT in 6 anesthetized pigs, and renal clearance of (11)C-metformin was compared with renal clearance of (51)Cr-ethylenediaminetetraacetic acid (EDTA). Formation of (11)C metabolites was investigated by analysis of blood and urine samples. The radiochemical yield of (11)C-metformin was 15% ± 3% (n= 40, decay-corrected), and up to 1.5 GBq of tracer were produced with a radiochemical purity greater than 95% in less than 30 min. Dose-dependent uptake of (11)C-metformin in LLC-PK1 cells was rapid. Rat small-animal PET images showed (11)C-metformin uptake in the kidney and liver, the kinetics of which were changed after challenging animals with OCT inhibitors. In pigs, 80% of the injected metformin dose was rapidly present in the kidney, and a high dose of metformin caused a delayed renal uptake and clearance compared with baseline consistent with transporter-mediated competition. Renal clearance of (11)C-metformin was approximately 3 times the renal clearance of (51)Cr-EDTA. We successfully synthesized an (11)C-metformin tracer, and PET studies in rats and pigs showed a rapid kidney uptake from the blood and excretion into the bladder similar to other radiopharmaceuticals developed for γ-camera renography. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Ontogenesis of uptake and deamination of 5-hydroxytryptamine, dopamine and beta-phenylethylamine in isolated perfused lung and lung homogenates from rats.

PubMed Central

Ben-Harari, R. R.; Youdim, M. B.

1981-01-01

1. Uptake of 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) was studied in perfused lung from male rats between 10 and 70 days old. 2. Monoamine oxidase (MAO) activity towards 5-HT, PEA and dopamine was studied in homogenate preparations of lung from rats aged between 5 and 80 days. 3. Uptake of 5-HT (10 microM) decreased throughout the age range studied but uptake of PEA (50 microM) increased for the first 30 days and beyond this age it decreased. Metabolites formed for both amines reflected the changes in uptake. 4. MAO activity deaminating 5-HT is well developed by day 10 and reaches its maximum by day 40. For dopamine and PEA, MAO activity remained low until day 20, and the developed rapidly, reaching a maximum by day 40 for dopamine; activity towards PEA did not reach a maximum by day 80. 5. These results show that uptake and MAO activity changes with age and thus the lung responds like other tissues. 6. These results also demonstrate the independent development of uptake and MAO activity towards 5-HT, PEA and dopamine. PMID:7284689

Light intensity affects the uptake and metabolism of glycine by pakchoi (Brassica chinensis L.)

NASA Astrophysics Data System (ADS)

Ma, Qingxu; Cao, Xiaochuang; Wu, Lianghuan; Mi, Wenhai; Feng, Ying

2016-02-01

The uptake of glycine by pakchoi (Brassica chinensis L.), when supplied as single N-source or in a mixture of glycine and inorganic N, was studied at different light intensities under sterile conditions. At the optimal intensity (414 μmol m-2 s-1) for plant growth, glycine, nitrate, and ammonium contributed 29.4%, 39.5%, and 31.1% shoot N, respectively, and light intensity altered the preferential absorption of N sources. The lower 15N-nitrate in root but higher in shoot and the higher 15N-glycine in root but lower in shoot suggested that most 15N-nitrate uptake by root transported to shoot rapidly, with the shoot being important for nitrate assimilation, and the N contribution of glycine was limited by post-uptake metabolism. The amount of glycine that was taken up by the plant was likely limited by root uptake at low light intensities and by the metabolism of ammonium produced by glycine at high light intensities. These results indicate that pakchoi has the ability to uptake a large quantity of glycine, but that uptake is strongly regulated by light intensity, with metabolism in the root inhibiting its N contribution.

How does altered precipitation and annual grass invasion affect plant N uptake in a native semi-arid shrub community?

NASA Astrophysics Data System (ADS)

Mauritz, M.; Lipson, D.; Cleland, E. E.

2012-12-01

Climate change is expected to alter precipitation patterns, which will change the timing and amount of plant resources. Precipitation patterns determine water and nitrogen (N) availability, because water stimulates microbial N turnover and N transport. In order for plants to utilize water and N, they must coincide with the phenology and meet physiological requirements of the plant. As resource supply shifts, differences in species' ability to acquire resources will affect plant community composition. Semiarid ecosystems, such as shrublands in Southern California, are particularly sensitive to shifts in precipitation because they are severely water limited. This study takes advantage of the altered phenology and resource demands presented by invasive annual grasses in a native semiarid shrubland. The goal is to understand how altered precipitation patterns affect plant N uptake. Rainfall levels were manipulated to 50% and 150% of ambient levels. It is expected that higher rainfall levels promote annual grass invasion because grasses have higher water and N requirements and begin to grow earlier in the season than shrubs. A 15N tracer was added with the first rain event and plant samples were collected regularly to track the movement of N into the plants. Net soil N accumulation was determined using resin bags. Invasive grasses altered the timing and amount of N uptake but amount of rainfall had less effect on N distribution. 15N was detected sooner and at higher level in grasses than shrubs. 24hours after the first rain event 15N was detectable in grasses, 15N accumulated rapidly and peaked 2 months earlier than shrubs. Shrub 15N levels remained at pre-rain event levels for the first 2 months and began to increase at the beginning of spring, peak mid-spring and decline as the shrubs entered summer dormancy. One year later 15N levels in annual grass litter remained high, while 15N levels in shrubs returned to initial background levels as a result of resorption. 15N concentrations are more variable in grasses which could indicate higher plasticity in grass N uptake compared to shrubs. Resin N supports the 15N patterns. Resin N declined more rapidly under grasses and was lower than under shrubs, presumably due to high grass N uptake. Resin N was particularly high under shrubs in wetter conditions indicating that shrubs could not take advantage of high N supply. Together the 15N and resin N patterns indicate that grasses accumulate more N and begin N uptake earlier in the season than shrubs. Although 15N did not differ in response to rainfall, invasion alters the distribution of N in the system. Rain was only manipulated for one growing season; multiple years of altered precipitation may yield significant differences. Early season N uptake by grasses, the low variability in shrub 15N and low shrub 15N in wetter conditions, despite high resin N, indicates that N competition between invasive grasses and native shrubs is weak. If N supply is sufficient for shrub demands, invasive grasses and shrubs could coexist. This study contributes to a broader understanding of how changes in resource supply, plant phenology and functional type interact and respond to climate change.

Mechanisms of vitamin K transport and metabolism in Swiss 3T3 mouse fibroblasts

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

Canfield, L.M.; Townsend, A.F.; Hibbs, D.B.

Transport of vitamin K into isolated fibroblasts was followed using /sup 3/H vitamin K/sub 1/. The initial rate is saturable by 5 min. at 25..mu..M vitamin K with a Km(app) of 10..mu..M and V/sub max/ of 50 pmols/min/10/sup 6/ cells. Kinetics of uptake are biphasic with a second slower rate ensuing after 10 minutes. Insensitivity of the initial rate of uptake to FCCP or ouabain indicates an ATP-independent transport mechanism. Specificity of transport is shown by competition of uptake of /sup 3/H vitamin K by unlabelled vitamin and strong (>90%) inhibition of the initial rate by equimolar concentrations of themore » vitamin K analog, Chloro-K. In addition, following uptake, both vitamins K/sub 1/ and K/sub 2/ are metabolized to their respective epoxides. Vitamin K/sub 1/ epoxide is also transported into fibroblasts and metabolized to the parent quinone in a Warfarin-sensitive reaction. Following alkaline hydrolysis of isolated intracellular protein, the vitamin K-dependent amino acid, gamma carboxyglutamic acid (gla) was detected. It is concluded that vitamin K is specifically transported into fibroblasts and metabolized via the classical pathway described in liver with the concomitant production of vitamin K-dependent proteins.« less

Hydrothermal stability of SAPO-34 for refrigeration and air conditioning applications

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

Chen, Haijun; Cui, Qun, E-mail: cuiqun@njtech.edu.cn; Wu, Juan

Graphical abstract: The SAPO-34 was synthesized by a hydrothermal method using diethylamine as a template. Water adsorption strength on SAPO-34 is between that on 13X and A type silica gel. During 100–400 Pa, the water uptake on SAPO-34 increases sensitively to pressure, and equilibrium water uptake reaches 0.35 kg/kg, 25% higher than 13X. SAPO-34 shows no significant reduced cyclic water uptake over 60 cycles. Most of the initial SAPO-34 phase is restored, while the regular cubic-like morphology is well maintained, and the specific surface area only decreases by 8.6%. - Highlights: • Water adsorption strength on SAPO-34 is between thatmore » on 13X and A type silica gel. During 100–400 Pa, the water uptake on SAPO-34 increases sensitively to pressure, and equilibrium water uptake reaches 0.35 kg/kg, 25% higher than 13X. • SAPO-34 with diethylamine as the template shows no significant reduced cyclic water uptake over 60 cycles, and most of the initial SAPO-34 phase is well maintained. • SAPO-34 has an excellent adsorption performance and a good hydrothermal stability, thus is promising for application in adsorption refrigeration. - Abstract: Hydrothermal stability is one of the crucial factors in applying SAPO-34 molecular sieve to adsorption refrigration. The SAPO-34 was synthesized by a hydrothermal method using diethylamine as a template. Both a vacuum gravimetric method and an intelligent gravimetric analyzer were applied to analyze the water adsorption performance of SAPO-34. Cyclic hydrothermal performance was determined on the modified simulation adsorption refrigeration test rig. Crystal phase, morphology, and porosity of SAPO-34 were characterized by X-ray diffraction, scanning electron microscopy, and N{sub 2} sorption, respectively. The results show that, water adsorption strength on SAPO-34 is between that on 13X and A type silica gel. During 100–400 Pa, the water uptake on SAPO-34 increases sensitively to pressure, and equilibrium water uptake reaches 0.35 kg/kg, 25% higher than 13X. SAPO-34 shows no significant reduced cyclic water uptake over 60 cycles. Most of the initial SAPO-34 phase is restored, while the regular cubic-like morphology is well maintained, and the specific surface area only decreases by 8.6%.« less

Development of accelerated net nitrate uptake. [Zea mays L

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

MacKown, C.T.; McClure, P.R.

1988-05-01

Upon initial nitrate exposure, net nitrate uptake rates in roots of a wide variety of plants accelerate within 6 to 8 hours to substantially greater rates. Effects of solution nitrate concentrations and short pulses of nitrate ({le}1 hour) upon nitrate-induced acceleration of nitrate uptake in maize (Zea mays L.) were determined. Root cultures of dark-grown seedlings, grown without nitrate, were exposed to 250 micromolar nitrate for 0.25 to 1 hour or to various solution nitrate concentration (10-250 micromolar) for 1 hour before returning them to a nitrate-free solution. Net nitrate uptake rates were assayed at various periods following nitrate exposuremore » and compared to rates of roots grown either in the absence of nitrate (CaSO{sub 4}-grown) or with continuous nitrate for at least 20 hours. Three hours after initial nitrate exposure, nitrate pulse treatments increased nitrate uptake rates three- to four-fold compared to the rates of CaSO{sub 4}-grown roots. When cycloheximide (5 micrograms per milliliter) was included during a 1-hour pulse with 250 micromolar nitrate, development of the accelerated nitrate uptake state was delayed. Otherwise, nitrate uptake rates reached maximum values within 6 hours before declining. Maximum rates, however, were significantly less than those of roots exposed continuously for 20, 32, or 44 hours. Pulsing for only 0.25 hour with 250 micromolar nitrate and for 1 hour with 10 micromolar caused acceleration of nitrate uptake, but the rates attained were either less than or not sustained for a duration comparable to those of roots pulsed for 1 hour with 250 micromolar nitrate. These results indicate that substantial development of nitrate-induced accelerated nitrate uptake state can be achieved by small endogenous accumulations of nitrate, which appear to moderate the activity or level of root nitrate uptake.« less

Mechanism and developmental changes in iron transport across the blood-brain barrier.

PubMed

Morgan, Evan H; Moos, Torben

2002-01-01

Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

Effect of interfacial composition on uptake of curcumin-piperine mixtures in oil in water emulsions by Caco-2 cells.

PubMed

Gülseren, İbrahim; Guri, Anilda; Corredig, Milena

2014-06-01

Encapsulation in lipid particles is often proposed as a solution to improve curcumin bioavailability. This bioactive molecule has low water solubility and rapidly degrades during digestion. In the present study, the uptake of curcumin from oil in water emulsions, prepared with two different emulsifiers, Tween 20 and Poloxamer 407, was investigated to determine the effect of interfacial composition on absorption. Piperine was added to the curcumin to limit the degradation of curcumin because it is known to inhibit β-glucuronidase activity. The emulsions were administered to Caco-2 cell cultures, which is used as a model for intestinal uptake, and the recovery of curcumin was measured. The curcumin uptake was significantly affected by the type of interface, and the extent of curcumin uptake improved significantly by piperine addition only in the case of oil-in-water emulsions stabilized by Poloxamer 407. This work provides further evidence of the importance of interfacial composition on the delivery of bioactives.

Fate and effects of nitrogen and phosphorus in shallow vegetated aquatic ecosystems

USGS Publications Warehouse

Fairchild, James F.; Vradenburg, Leigh Ann

2006-01-01

Nitrate concentrations have greatly increased in streams and rivers draining agricultural regions of the Midwestern United States, increasing nitrate transport to the Gulf of Mexico has been implicated in the hypoxic conditions that threaten the productivity of marine fisheries. Increases in nitrate concentrations have been attributed to a combination of factors including agricultural expansion, increased nitrogen application rates, increased tile drainage, and loss of riparian Wetlands, These landscape-level changes have resulted in a decreased natural capacity for nitrogen uptake, removal, and cycling back to the atmosphere. Land managers are increasingly interested in using wetland construction and rehabilitation as a management practice to reduce loss of nitrate from the terrestrial systems. Yet, relatively little is known about the limnological factors involved in nitrate removal by Wetland systems.We conducted a series of studies from 1999-2000 to investigate the functional capacity of shallow, macrophyte-dominated pond wetland systems for uptake, assimilation, and retention of nitrogen (N) and phosphorus (P). We evaluated four factors that were hypothesized to influence nutrient uptake and assimilation: 1) nitrate loading rates; 2) nitrogen to phosphorus (N.P) ratios; 3) frequency of dosing/application; and 4) timing of dose initiation.Nutrient assimilation was rapid; store than 90% of added nutrients were removed from the water column in all treatments. Neither variation in N:P ratios (evaluated range, <13:1 to -114.1), frequency of application (weekly or bi-weekly), nor liming of dose initiation relative to macrophyte development (0%, 15-25%, or 75-90% maximum biomass) had significant effects on nutrient assimilation of wetland community dynamics. Maximum loading of nitrate (60 g N/m2 2.4 g P/m2) applied as six weekly doses stimulated algal communities, but inhibited macrophyte communities.Predicted shifts from a stable state of macrophyte- to phytoplankton-dominance did not occur due to nutrient additions. Macrophytes, phytoplankton, and the sediment surface were all significant factors in the removal of nitrate from the Water column. Overall, these shallow macrophyte-dominated systems provided an efficient means of removing nutrients from the water column. Construction or rehabilitation of shallow, vegetated wetlands may offer promise as land management practices for nutrient removal in agricultural watersheds.

Nicotine transport in lung and non-lung epithelial cells.

PubMed

Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

2017-11-01

Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

Series: Clinical Epidemiology in South Africa. Paper 1: Evidence-based health care and policy in Africa: past, present, and future.

PubMed

Young, Taryn; Garner, Paul; Clarke, Mike; Volmink, Jimmy

2017-03-01

Africa has high disease burden and health system challenges but is making progress in recognizing, accepting, and adopting evidence-based health care (EBHC). In this article, we reflect on the developments of the past 2 decades and consider further steps that will help with the translation of reliable research results into the decision making process. There has been a rapid growth in various initiatives to promote EBHC in the African region. These include the conduct and reporting of primary and secondary research, research capacity development and supportive initiatives, access to information, and work with decision makers in getting research into clinical guidelines and health policies. Much, however, still needs to be done to improve the impact on health in the region. A multipronged approach consisting of regionally relevant well-conducted research addressing priority health problems, increased uptake of research in health care policy and practice, dedicated capacity development initiatives to support the conduct as well as use of research, facilitated by wider collaboration, and equitable partnerships will be important. Working together in mutually supporting partnerships is key to advancing both evidence-informed health care practices and better health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Long-Acting Reversible Contraceptive Placement Among Active-Duty U.S. Army Servicewomen.

PubMed

Erickson, Anne K; Nelson, D Alan; Shaw, Jonathan G; Loftus, Pooja D; Kurina, Lianne M; Shaw, Kate A

2017-05-01

To quantify uptake of long-acting reversible contraceptives (LARC)-intrauterine devices (IUDs) and hormonal implants-among U.S. Army active-duty female soldiers and identify characteristics associated with uptake. This retrospective cohort study used the Stanford Military Data Repository, which includes all digitally recorded health encounters for active-duty U.S. Army soldiers from 2011 to 2014. We analyzed data from women aged 18-44 years to assess rates of LARC initiation using medical billing codes. We then evaluated predictors of LARC initiation using multivariable regression. Among 114,661 servicewomen, 14.5% received a LARC method; among those, 60% received an IUD. Intrauterine device insertions decreased over the study period (38.7-35.9 insertions per 1,000 women per year, β=0.14, 95% confidence interval [CI] -0.23 to -0.05, P<.05), whereas LARC uptake increased, driven by an increase in implant insertions (20.3-35.4/1,000 women per year, β=0.41, CI 0.33-0.48, P<.001). Younger age was a positive predictor of LARC uptake: 32.4% of IUD users and 62.6% of implant users were in the youngest age category (18-22 years) compared with 9.6% and 2.0% in the oldest (36-44 years). The likelihood of uptake among the youngest women (compared with oldest) was most marked for implants (adjusted relative risk 7.12, CI 5.92-8.55; P<.001). A total of 26.2% of IUD users had one child compared with 13.2% among non-LARC users (adjusted relative risk 1.94, CI 1.85-2.04, P<.001). The majority (52.2%) of those initiating IUDs were married, which was predictive of uptake over never-married women (adjusted relative risk 1.52, CI 1.44-1.59, P<.001). Among servicewomen, we observed low but rising rates of LARC insertion, driven by increasing implant use. Unmarried and childless soldiers were less likely to initiate LARC. These findings are consistent with potential underutilization and a need for education about LARC safety and reversibility in a population facing unique consequences for unintended pregnancies.

Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired-tracer dilution: studies with calcium and choline.

PubMed

Sweiry, J H; Page, K R; Dacke, C G; Abramovich, D R; Yudilevich, D L

1986-12-01

Rapid uptake and efflux of 45Ca2+ and [3H]choline at the maternal and fetal interfaces of the syncytiotrophoblast in the dually-perfused human placenta was investigated by application of the single circulation paired-tracer dilution method (Yudilevich, Eaton, Short & Leichtweiss 1979). Cotyledons were perfused with Krebs-bicarbonate containing dextran (30 g/l; MW = 60-70,000) at 20 and 6 ml/min on maternal and fetal sides, respectively. The paired-tracer (test substrate and extracellular marker) technique consisted of an intra-arterial injection of a tracer bolus, followed by venous sampling over 5-6 min. There was a rapid (sec) uptake of 45Ca2+, followed by backflux (efflux into the ipsilateral circulation) which, over 5-6 min, was 59-100% on the fetal side. It was more variable but generally lower on the maternal interface. At 0.1 mM calcium, 45Ca2+ maximal uptake (Umax) was about 53% on the fetal side but on the maternal side it was variable and averaged 17%. At 2.4 mM calcium fetal side Umax was reduced to 40%. However, on the maternal side the effect was not consistent. Unidirectional influx (nmol/min per g) appeared to be not different on the two sides of the placenta. For [3H]choline (in choline-free perfusates) Umax was about 50% and 30% on fetal and maternal sides, respectively; tracer backflux was variable on the maternal side and averaged 50% on the fetal side. [3H]Choline uptake was highly inhibited by either 1.0 mM choline or the specific competitive inhibitor, hemicholinium-3 (0.1 mM). Specific transplacental transfer of 45Ca2+ (i.e. in excess of the extracellular marker) was not significant in either direction. For [3H]choline there was an apparent small excess (about 4%) preferential towards the fetal circulation. These findings in the human placenta are similar to those demonstrated previously in the guinea-pig placenta which suggested the existence of specific transport systems for choline and calcium on both sides of the syncytiotrophoblast.

The interplay of contextual elements in implementation: an ethnographic case study.

PubMed

McCullough, Megan B; Chou, Ann F; Solomon, Jeffrey L; Petrakis, Beth Ann; Kim, Bo; Park, Angela M; Benedict, Ashley J; Hamilton, Alison B; Rose, Adam J

2015-02-14

Contextual elements have significant impact on uptake of health care innovations. While existing conceptual frameworks in implementation science suggest contextual elements interact with each other, little research has described how this might look in practice. To bridge this gap, this study identifies the interconnected patterns among contextual elements that influence uptake of an anticoagulation clinic improvement initiative. We completed 51 semi-structured interviews and ethnographic observations across five case study sites involved in an evidence-based practice (EBP) quality improvement initiative. We analyzed data in NVivo 10 using an a priori approach based on the Promoting Action on Research Implementation in Health Services (PARIHS) model and an emergent thematic analysis. Key contextual elements, such as leadership, teamwork, and communication, interacted with each other in contributing to site-level uptake of the EBP, often yielding results that could not be predicted by looking at just one of these elements alone. Sites with context conducive to change in these areas predictably had high uptake, while sites with uniformly weak contextual elements had low uptake. Most sites presented a mixed picture, with contextual elements being strongly supportive of change in some areas and weak or moderate in others. In some cases, we found that sites with strong context in at least one area only needed to have adequate context in other areas to yield high uptake. At other sites, weak context in just one area had the potential to contribute to low uptake, despite countervailing strengths. Even a site with positive views of EBPs could not succeed when context was weak. Interrelationships among different contextual elements can act as barriers to uptake at some sites and as facilitators at others. Accounting for interconnections among elements enables PARIHS to more fully describe the determinants of successful implementation as they operate in real-world settings.

Bio sorption of strontium from aqueous solution by New Strain Bacillus sp. GTG-83

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

Tajer Mohammad Ghazvini, P.; Ghorbanzadeh Mashkani, S.; Ghafourian, H.

Attempt was made to isolate bacterial strains capable of removing Sr biologically. In this study we collected ten different water samples from naturally radioactive spring Neydasht in Iran and bacterial strains samples isolated. Initial screening of a total of 50 bacterial isolates resulted in selection of one strain. The strain showed maximum adsorption capacity with 55 mg Sr/g dry wt. It was tentatively identified as Bacillus sp. according to morphological and biochemical properties and called strain GTG-83. Studies indicated that Bacillus sp. GTG-83 was able to grow aerobically in the presence of 50 mM SrCl{sub 2} but showed severe growthmore » inhibition at levels above that concentration. The bio-sorption capacity of Bacillus sp. GTG-83 strongly depends on solution pH, and the maximum Sr sorption capacity of Bacillus sp. GTG-83 were obtained at pH 10 independent of the absence or the presence of increasing concentrations of salt (MgCl{sub 2}). Sr-salt bio-sorption studies were also performed at this pH values. Equilibrium uptakes of Sr increased with increasing Sr concentrations up to 250 mg/l for Bacillus sp. GTG-83. Maximum bio-sorption of Sr was obtained at temperatures in the range of 30-35 deg. C. Bacillus sp. GTG-83 bio-sorbed 97 mg Sr/g dry wt at 100 mg/l initial Sr concentration without salt medium (MgCl{sub 2}). When salt concentration (MgCl{sub 2}) increased to 15% (w/v), these values dropped to 23.6 mg Sr/g dry wt at the same conditions. Uptake of Sr within 5 min of incubation was relatively rapid and the absorption continued slowly thereafter. (authors)« less

Insulin-Responsive Compartments Containing GLUT4 in 3T3-L1 and CHO Cells: Regulation by Amino Acid Concentrations

PubMed Central

Bogan, Jonathan S.; McKee, Adrienne E.; Lodish, Harvey F.

2001-01-01

In fat and muscle, insulin stimulates glucose uptake by rapidly mobilizing the GLUT4 glucose transporter from a specialized intracellular compartment to the plasma membrane. We describe a method to quantify the relative proportion of GLUT4 at the plasma membrane, using flow cytometry to measure a ratio of fluorescence intensities corresponding to the cell surface and total amounts of a tagged GLUT4 reporter in individual living cells. Using this assay, we demonstrate that both 3T3-L1 and CHO cells contain intracellular compartments from which GLUT4 is rapidly mobilized by insulin and that the initial magnitude and kinetics of redistribution to the plasma membrane are similar in these two cell types when they are cultured identically. Targeting of GLUT4 to a highly insulin-responsive compartment in CHO cells is modulated by culture conditions. In particular, we find that amino acids regulate distribution of GLUT4 to this kinetically defined compartment through a rapamycin-sensitive pathway. Amino acids also modulate the magnitude of insulin-stimulated translocation in 3T3-L1 adipocytes. Our results indicate a novel link between glucose and amino acid metabolism. PMID:11416153

Rapid changes in local extracellular rat brain glucose observed with an in vivo glucose sensor.

PubMed

Hu, Y; Wilson, G S

1997-04-01

A needle-type electrochemically based microsensor for glucose (110 microns o.d.) is described. This sensor, designed for monitoring transient glucose content changes in response to neural stimuli, has a response time of approximately 5 s and has been shown to be free of interference from endogenous electroactive species such as ascorbate, urate, and various neurotransmitters. It exhibits linear response to glucose up to 10 mM. The usefulness of the sensor has been demonstrated by examining the time-dependent interstitial glucose concentration in the rat hippocampus in response to KCl depolarization and by stimulation of glutamate neurons through a perforant pathway. Simultaneous monitoring of oxygen is also carried out and demonstrates that for both oxygen and glucose there is substantial local depletion of both species and that their pools are replenished by increased regional cerebral blood flow. The transient initial rapid (10-13 s) decrease up to 20-34%, observed on a time scale comparable to that for neurotransmitter release, may be involved in a recently suggested astrocytic uptake for glutamate-stimulated aerobic glycolysis possibly needed to meet energy homeostasis in brain. These studies demonstrate the importance of microsensors in monitoring transient events linked to neuronal stimulation.

Can smoking initiation contexts predict how adult Aboriginal smokers assess their smoking risks? A cross-sectional study using the 'Smoking Risk Assessment Target'.

PubMed

Gould, Gillian Sandra; Watt, Kerrianne; West, Robert; Cadet-James, Yvonne; Clough, Alan R

2016-07-07

Smoking prevalence is slow to reduce among Indigenous Australians of reproductive age. We analysed the relationships between age of smoking initiation, recalled initiation influences and self-assessment of smoking risks in Aboriginal smokers. A community-based cross-sectional survey of Aboriginal smokers aged 18-45 years (N=121; 58 men) was undertaken, using single-item measures. The Smoking Risk Assessment Target (SRAT) as the primary outcome measure enabled self-assessment of smoking risks from 12 options, recategorised into 3 groups. Participants recalled influences on their smoking initiation. Multinomial logistic regression modelling included age, gender, strength of urges to smoke, age at initiation (regular uptake) and statistically significant initiation influences on χ(2) tests ('to be cool', alcohol and cannabis). Frequent initiation influences included friends (74%; SD 0.44), family (57%; SD 0.5) and alcohol (40%; SD 0.49). 54% (n=65) of smokers had the highest risk perception on the SRAT, selected by those who cared about the smoking risks and intended to quit soon. On multivariate analyses, compared with the highest level of SRAT, male gender, lower age of uptake and strong urges to smoke were significantly associated with the lowest level of SRAT, selected by those who refuted risks or thought they could not quit. Lower age of uptake and alcohol were associated with mid-level of SRAT, selected by those who cared about smoking risks, but did not consider quitting as a priority. Characteristics of smoking initiation in youth may have far-reaching associations with how smoking risks are assessed by adults of reproductive age, and their intentions to quit smoking. Becoming a regular smoker at under the age of 16 years, and influences of alcohol on smoking uptake, were inversely associated with high-level assessment of smoking risks and intention to quit in regional Aboriginal smokers. The SRAT may help tailor approaches to Indigenous smoking cessation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Can smoking initiation contexts predict how adult Aboriginal smokers assess their smoking risks? A cross-sectional study using the ‘Smoking Risk Assessment Target’

PubMed Central

Gould, Gillian Sandra; Watt, Kerrianne; West, Robert; Cadet-James, Yvonne; Clough, Alan R

2016-01-01

Objectives Smoking prevalence is slow to reduce among Indigenous Australians of reproductive age. We analysed the relationships between age of smoking initiation, recalled initiation influences and self-assessment of smoking risks in Aboriginal smokers. Design, setting and participants A community-based cross-sectional survey of Aboriginal smokers aged 18–45 years (N=121; 58 men) was undertaken, using single-item measures. The Smoking Risk Assessment Target (SRAT) as the primary outcome measure enabled self-assessment of smoking risks from 12 options, recategorised into 3 groups. Participants recalled influences on their smoking initiation. Multinomial logistic regression modelling included age, gender, strength of urges to smoke, age at initiation (regular uptake) and statistically significant initiation influences on χ2 tests (‘to be cool’, alcohol and cannabis). Results Frequent initiation influences included friends (74%; SD 0.44), family (57%; SD 0.5) and alcohol (40%; SD 0.49). 54% (n=65) of smokers had the highest risk perception on the SRAT, selected by those who cared about the smoking risks and intended to quit soon. On multivariate analyses, compared with the highest level of SRAT, male gender, lower age of uptake and strong urges to smoke were significantly associated with the lowest level of SRAT, selected by those who refuted risks or thought they could not quit. Lower age of uptake and alcohol were associated with mid-level of SRAT, selected by those who cared about smoking risks, but did not consider quitting as a priority. Conclusions Characteristics of smoking initiation in youth may have far-reaching associations with how smoking risks are assessed by adults of reproductive age, and their intentions to quit smoking. Becoming a regular smoker at under the age of 16 years, and influences of alcohol on smoking uptake, were inversely associated with high-level assessment of smoking risks and intention to quit in regional Aboriginal smokers. The SRAT may help tailor approaches to Indigenous smoking cessation. PMID:27388350

Short-term fate of dietary dieldrin in the digestive tract of juvenile lake trout (Salvelinus namaycush)

USGS Publications Warehouse

Stewart, Donald J.; Stein, Roy A.

1974-01-01

Short-term fate of dietary dieldrin in the digestive tract of fishes is poorly known. Studies of the uptake, distribution, and elimination of chlorinated hydrocarbons have suggested that uptake or degradation is rapid in the intestine (GROSS 1969; MACEK et al. 1970; GRZENDA et al. 1970, 1971). The present study was designed to determine the short-term fate of a single oral dose of dieldrin in the digestive tract of lake trout (Salvelinus namaycush).

Long-Term Management Strategy for Dredged Material Disposal for Naval Facilities at Pearl Harbor, Hawaii Phase III - Analysis of Alternatives and Development of an LTMS

DTIC Science & Technology

2000-03-01

are needed to restrict contaminants losses via the leachate and volatilization pathways. Plant uptake testing indicated a potential need to restrict...or control future use of the site, to amend the material with soil additives, to phytoremediate , or to provide a final surface cover of clean...initial release including toxicity and bioaccumulation, effluent, runoff, leachate , plant uptake, upland and aquatic animal uptake, and

Theoretic criteria for antibody penetration into solid tumors and micrometastases.

PubMed

Thurber, Greg M; Zajic, Stefan C; Wittrup, K Dane

2007-06-01

Targeting tumors with antibody-based therapeutics is a complex task presenting multiple kinetic barriers. Antibody internalization and clearance inhibit uptake both in solid tumors, limited by tumor vascular permeability, and in micrometastases, limited by diffusion. A modeling exercise is used to introduce 2 simple criteria that must be less than unity for saturation of both tumors and micrometastases. The clearance modulus and the Thiele modulus are ratios of the plasma clearance rate and antibody catabolism, respectively, to the tumor tissue penetration rate. Even low rates of antigen internalization from constitutive membrane turnover can significantly retard antibody penetration. Rapid clearance of single-chain variable fragments also hinders uptake, often more than counterbalancing their more rapid extravasation and diffusion. The model illustrates that with the large resistance from the tumor capillary, antibodies may be more suitable for targeting micrometastases than vascularized tumors.

G4-Tetra DNA Duplex Induce Lung Cancer Cell Apoptosis in A549 Cells

NASA Astrophysics Data System (ADS)

Xu, Xiaobo; Zhao, YiZhuo; Lu, Hu; Fu, Cuiping; Li, Xiao; Jiang, Liyan; Li, Shanqun

2016-10-01

The specific DNA is typically impermeable to the plasma membrane due to its natural characters, but DNA tetra structures (DTNs) can be readily uptake by cells in the absence of transfection agents, providing a new strategy to deliver DNA drugs. In this research, the delivery efficiency of tetrahedral DNA nanostructures was measured on adenocarcinomic human alveolar basal epithelial (A549) cells via delivering AS1411 (G4). The DNA tetra-AS1411 complex was rapidly and abundantly uptake by A549 cells, and the induced apoptosis was enhanced. Furthermore, biodistribution in mouse proved the rapid clearance from non-targeted organs in vivo. This study improved the understanding of potential function in DNA-based drug delivery and proved that DTNs-AS1411 could be potentially useful for the treatment of lung cancer.

Retention in care and reasons for discontinuation of lifelong antiretroviral therapy in a cohort of Cameroonian pregnant and breastfeeding HIV-positive women initiating 'Option B+' in the South West Region.

PubMed

Atanga, Pascal N; Ndetan, Harrison T; Achidi, Eric A; Meriki, Henry D; Hoelscher, Michael; Kroidl, Arne

2017-02-01

To assess linkage and retention in care along the PMTCT cascade in HIV-positive pregnant and breastfeeding women initiating Option B+ in Cameroon. We prospectively determined uptake of HIV testing and counselling (HTC), uptake of ART and retention in care after Option B+ initiation between October 2013 and December 2014 in pregnant and breastfeeding women from five sites within the Kumba Health District. Retention in care was assessed over at least 12 months follow-up and estimated by Kaplan-Meier analysis. During follow-up, tracing outcomes and reasons for discontinuing treatment were documented. The uptake of HTC of 5813 women with unknown HIV status was 98.5%, 251 (4.4%) were newly diagnosed HIV positive, and ART uptake in women eligible to start Option B+ was 96.8%. We enrolled 268 women initiating lifelong ART in the follow-up. Overall, 65 (24.3%) discontinued treatment, either defined by loss to follow-up (44.6%) or actively stopped treatment (55.8%). Retention in care was 88.0% and 81.1% at 6 and 12 months, respectively. Discontinuation was significantly associated in multivariate analysis with small sites and high staff turnover [aOR 2.5 (95% CI 1.6, 3.9), P < 0.001]. Main reasons for stopping treatment were HIV status denial and stigma (52.8%), religious reasons (25.0%) and lack of transport fare (11.1%). We observed good uptake of HTC, ART and retention in care, which declined over time. Discontinuation of Option B+ was highest at small sites with a high staff turnover. Improved staffing, adequate task shifting and community interventions to track defaulters including reducing stigma and religious beliefs may improve Option B+ retention. © 2016 John Wiley & Sons Ltd.

Characterization of nanoparticle uptake by endothelial cells.

PubMed

Davda, Jasmine; Labhasetwar, Vinod

2002-02-21

Endothelium is an important target for drug or gene therapy because of its important role in the biological system. In this paper, we have characterized nanoparticle uptake by endothelial cells in cell culture. Nanoparticles were formulated using poly DL-lactide-co-glycolide polymer containing bovine serum albumin as a model protein and 6-coumarin as a fluorescent marker. It was observed that the cellular uptake of nanoparticles depends on the time of incubation and the concentration of nanoparticles in the medium. The uptake of nanoparticles was rapid with confocal microscopy demonstrating their localization mostly in the cytoplasm. The mitogenic study demonstrated biocompatability of nanoparticles with the cells. The study thus demonstrates that nanoparticles could be used for localizing therapeutic agents or gene into endothelial cells. Nanoparticles localized in the endothelium could provide prolonged drug effects because of their sustained release characterics, and also could protect the encapsulated agent from enzymatic degradation.

Carbon-11 choline: synthesis, purification, and brain uptake inhibition by 2-dimethylaminoethanol

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

Rosen, M.A.; Jones, R.M.; Yano, Y.

We report an improved method for the synthesis and purification of (11C)methylcholine from the precursors (11C)methyliodide and 2-dimethylaminoethanol (deanol). Preparation time, including purification, is 35 min postbombardment. Forty millicuries of purified injectable (11C)choline were produced with a measured specific activity of greater than 300 Ci/mmol and a radiochemical purity greater than 98%. The decay corrected radiochemical yield for the synthesis and purification was approximately 50%. Residual precursor deanol, which inhibits brain uptake of choline, is removed by a rapid preparative high performance liquid chromatography (HPLC) method using a reverse phase cyano column with a biologically compatible 100% water eluent. Evaporationmore » alone did not completely remove the deanol precursor. Brain uptake of the (11C)choline product was six times greater after HPLC removal of deanol because doses of less than 1 microgram/kg significantly inhibit (14C)choline brain uptake.« less

Rapid transporter regulation prevents substrate flow traffic jams in boron transport

PubMed Central

Sotta, Naoyuki; Duncan, Susan; Tanaka, Mayuki; Sato, Takafumi

2017-01-01

Nutrient uptake by roots often involves substrate-dependent regulated nutrient transporters. For robust uptake, the system requires a regulatory circuit within cells and a collective, coordinated behaviour across the tissue. A paradigm for such systems is boron uptake, known for its directional transport and homeostasis, as boron is essential for plant growth but toxic at high concentrations. In Arabidopsis thaliana, boron uptake occurs via diffusion facilitators (NIPs) and exporters (BORs), each presenting distinct polarity. Intriguingly, although boron soil concentrations are homogenous and stable, both transporters manifest strikingly swift boron-dependent regulation. Through mathematical modelling, we demonstrate that slower regulation of these transporters leads to physiologically detrimental oscillatory behaviour. Cells become periodically exposed to potentially cytotoxic boron levels, and nutrient throughput to the xylem becomes hampered. We conclude that, while maintaining homeostasis, swift transporter regulation within a polarised tissue context is critical to prevent intrinsic traffic-jam like behaviour of nutrient flow. PMID:28870285

Rapid transporter regulation prevents substrate flow traffic jams in boron transport.

PubMed

Sotta, Naoyuki; Duncan, Susan; Tanaka, Mayuki; Sato, Takafumi; Marée, Athanasius Fm; Fujiwara, Toru; Grieneisen, Verônica A

2017-09-05

Nutrient uptake by roots often involves substrate-dependent regulated nutrient transporters. For robust uptake, the system requires a regulatory circuit within cells and a collective, coordinated behaviour across the tissue. A paradigm for such systems is boron uptake, known for its directional transport and homeostasis, as boron is essential for plant growth but toxic at high concentrations. In Arabidopsis thaliana , boron uptake occurs via diffusion facilitators (NIPs) and exporters (BORs), each presenting distinct polarity. Intriguingly, although boron soil concentrations are homogenous and stable, both transporters manifest strikingly swift boron-dependent regulation. Through mathematical modelling, we demonstrate that slower regulation of these transporters leads to physiologically detrimental oscillatory behaviour. Cells become periodically exposed to potentially cytotoxic boron levels, and nutrient throughput to the xylem becomes hampered. We conclude that, while maintaining homeostasis, swift transporter regulation within a polarised tissue context is critical to prevent intrinsic traffic-jam like behaviour of nutrient flow.

The mechanism of thorium biosorption by Rhizopus arrhizus

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

Tsezos, M.; Volesky, B.

1982-04-01

Inactive cells of Rhizopus arrhizus have been documented to exhibit a high thorium biosorptive uptake (170 mg/g) from aqueous solutions. The mechanism of thorium sequestering by this biomass type was investigated following the same method as for the uranium biosorption emchanism. The thorium sequestering mechanism appeared somewhat different from that of uranium. Experimental evidence is presented which indicates that, at optimum biosorption pH (4), thorium coordinates with the nitroge of the chitin cell wall network and, in addition, more thorium is adsorbed by the external section of the fungal cell wall. At pH 2 the overall thorium uptake is reduced.more » The kinetic study of thorium biosorption revealed a very rapid rate of uptake. Unlike uranium at optimum solution pH, Fe/sup 2 +/ and Zn/sup 2 +/ did not interfere significantly with the thorium biosorptive uptake capacity of R. arrhizus.« less

Climate. Varying planetary heat sink led to global-warming slowdown and acceleration.

PubMed

Chen, Xianyao; Tung, Ka-Kit

2014-08-22

A vacillating global heat sink at intermediate ocean depths is associated with different climate regimes of surface warming under anthropogenic forcing: The latter part of the 20th century saw rapid global warming as more heat stayed near the surface. In the 21st century, surface warming slowed as more heat moved into deeper oceans. In situ and reanalyzed data are used to trace the pathways of ocean heat uptake. In addition to the shallow La Niña-like patterns in the Pacific that were the previous focus, we found that the slowdown is mainly caused by heat transported to deeper layers in the Atlantic and the Southern oceans, initiated by a recurrent salinity anomaly in the subpolar North Atlantic. Cooling periods associated with the latter deeper heat-sequestration mechanism historically lasted 20 to 35 years. Copyright © 2014, American Association for the Advancement of Science.

Offering self-administered oral HIV testing to truck drivers in Kenya to increase testing: a randomized controlled trial.

PubMed

Kelvin, Elizabeth A; George, Gavin; Mwai, Eva; Nyaga, Eston; Mantell, Joanne E; Romo, Matthew L; Odhiambo, Jacob O; Starbuck, Lila; Govender, Kaymarlin

2018-01-01

We conducted a randomized controlled trial among 305 truck drivers from two North Star Alliance roadside wellness clinics in Kenya to see if offering HIV testing choices would increase HIV testing uptake. Participants were randomized to be offered (1) a provider-administered rapid blood (finger-prick) HIV test (i.e., standard of care [SOC]) or (2) a Choice between SOC or a self-administered oral rapid HIV test with provider supervision in the clinic. Participants in the Choice arm who refused HIV testing in the clinic were offered a test kit for home use with phone-based posttest counseling. We compared HIV test uptake using the Mantel Haenszel odds ratio (OR) adjusting for clinic. Those in the Choice arm had higher odds of HIV test uptake than those in the SOC arm (OR = 1.5), but the difference was not statistically significant (p = 0.189). When adding the option to take an HIV test kit for home use, the Choice arm had significantly greater odds of testing uptake (OR = 2.8, p = 0.002). Of those in the Choice arm who tested, 26.9% selected the SOC test, 64.6% chose supervised self-testing in the clinic, and 8.5% took a test kit for home use. Participants varied in the HIV test they selected when given choices. Importantly, when participants who refused HIV testing in the clinic were offered a test kit for home use, an additional 8.5% tested. Offering truck drivers a variety of HIV testing choices may increase HIV testing uptake in this key population.

Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma.

PubMed

Liu, Xiang; Pham, Tien Q; Berghofer, Paula; Chapman, Janette; Greguric, Ivan; Mitchell, Peter; Mattner, Filomena; Loc'h, Christian; Katsifis, Andrew

2008-10-01

A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. [(123)I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. The iodonicotinamides displayed low-affinity binding for sigma(1)-sigma(2) receptors (K(i)>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[(123)I]iodonicotinamide ([(123)I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ( approximately 8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [(123)I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [(123)I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [(123)I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. These findings suggest that [(123)I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.

Rapid Cycle Amine (RCA 2.0) System Development

NASA Technical Reports Server (NTRS)

Papale, William; O'Coin, James; Wichowski, Robert; Chullen, Cinda; Campbell, Colin

2012-01-01

The Rapid Cycle Amine (RCA) system is a low power assembly capable of simultaneously removing carbon dioxide (CO2) and humidity from an influent air steam and subsequent regeneration when exposed to a vacuum source. Two solid amine sorbent beds are alternated between an uptake mode and a regeneration mode. During the uptake mode, the sorbent is exposed to an air steam (ventilation loop) to adsorb CO2 and water vapor, while during the regeneration mode, the sorbent rejects the adsorbed CO2 and water vapor to a vacuum source. The two beds operate such that while one bed is in the uptake mode, the other is in the regeneration mode, thus continuously providing an on-service sorbent bed by which CO2 and humidity may be removed. A novel valve assembly provides a simple means of diverting the process air flow through the uptake bed while simultaneously directing the vacuum source to the regeneration bed. Additionally, the valve assembly is designed to allow for switching between uptake and regeneration modes with only one moving part while minimizing gas volume losses to the vacuum source by means of an internal pressure equalization step during actuation. The process can be controlled by a compact, low power controller design with several modes of operation available to the user. Together with NASA, United Technologies Corporation Aerospace Systems has been developing RCA 2.0 based on performance and design feedback on several sorbent bed test articles and valve design concepts. A final design was selected in November 2011 and fabricated and assembled between March and August 2012, with delivery to NASA-JSC in September 2012. This paper will provide an overview on the RCA system design and results of pre-delivery testing.

Sap fluxes from different parts of the rootzone modulate xylem ABA concentration during partial rootzone drying and re-wetting

PubMed Central

Pérez-Pérez, J. G.; Dodd, I. C.

2015-01-01

Previous studies with partial rootzone drying (PRD) irrigation demonstrated that alternating the wet and dry parts of the rootzone (PRD-Alternated) increased leaf xylem ABA concentration ([X-ABA]leaf) compared with maintaining the same wet and dry parts of the rootzone (PRD-Fixed). To determine the relative contributions of different parts of the rootzone to this ABA signal, [X-ABA]leaf of potted, split-root tomato (Solanum lycopersicum) plants was modelled by quantifying the proportional water uptake from different soil compartments, and [X-ABA]leaf responses to the entire pot soil-water content (θpot). Continuously measuring soil-moisture depletion by, or sap fluxes from, different parts of the root system revealed that water uptake rapidly declined (within hours) after withholding water from part of the rootzone, but was rapidly restored (within minutes) upon re-watering. Two hours after re-watering part of the rootzone, [X-ABA]leaf was equally well predicted according to θpot alone and by accounting for the proportional water uptake from different parts of the rootzone. Six hours after re-watering part of the rootzone, water uptake by roots in drying soil was minimal and, instead, occurred mainly from the newly irrigated part of the rootzone, thus [X-ABA]leaf was best predicted by accounting for the proportional water uptake from different parts of the rootzone. Contrary to previous results, alternating the wet and dry parts of the rootzone did not enhance [X-ABA]leaf compared with PRD-Fixed irrigation. Further work is required to establish whether altered root-to-shoot ABA signalling contributes to the improved yields of crops grown with alternate, rather than fixed, PRD. PMID:25740924

Sap fluxes from different parts of the rootzone modulate xylem ABA concentration during partial rootzone drying and re-wetting.

PubMed

Pérez-Pérez, J G; Dodd, I C

2015-04-01

Previous studies with partial rootzone drying (PRD) irrigation demonstrated that alternating the wet and dry parts of the rootzone (PRD-Alternated) increased leaf xylem ABA concentration ([X-ABA]leaf) compared with maintaining the same wet and dry parts of the rootzone (PRD-Fixed). To determine the relative contributions of different parts of the rootzone to this ABA signal, [X-ABA]leaf of potted, split-root tomato (Solanum lycopersicum) plants was modelled by quantifying the proportional water uptake from different soil compartments, and [X-ABA]leaf responses to the entire pot soil-water content (θpot). Continuously measuring soil-moisture depletion by, or sap fluxes from, different parts of the root system revealed that water uptake rapidly declined (within hours) after withholding water from part of the rootzone, but was rapidly restored (within minutes) upon re-watering. Two hours after re-watering part of the rootzone, [X-ABA]leaf was equally well predicted according to θpot alone and by accounting for the proportional water uptake from different parts of the rootzone. Six hours after re-watering part of the rootzone, water uptake by roots in drying soil was minimal and, instead, occurred mainly from the newly irrigated part of the rootzone, thus [X-ABA]leaf was best predicted by accounting for the proportional water uptake from different parts of the rootzone. Contrary to previous results, alternating the wet and dry parts of the rootzone did not enhance [X-ABA]leaf compared with PRD-Fixed irrigation. Further work is required to establish whether altered root-to-shoot ABA signalling contributes to the improved yields of crops grown with alternate, rather than fixed, PRD. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Rapid Cycle Amine (RCA 2.0) System Development

NASA Technical Reports Server (NTRS)

Papale, William; O'Coin, James; Wichowski, Robert; Chullen, Cinda; Campbell, Colin

2013-01-01

The Rapid Cycle Amine (RCA) system is a low-power assembly capable of simultaneously removing carbon dioxide (CO2) and humidity from an influent air steam and subsequent regeneration when exposed to a vacuum source. Two solid amine sorbent beds are alternated between an uptake mode and a regeneration mode. During the uptake mode, the sorbent is exposed to an air steam (ventilation loop) to adsorb CO2 and water (H2O) vapor, whereas during the regeneration mode, the sorbent rejects the adsorbed CO2 and H2O vapor to a vacuum source. The two beds operate such that while one bed is in the uptake mode, the other is in the regeneration mode, thus continuously providing an on-service sorbent bed by which CO2 and humidity may be removed. A novel valve assembly provides a simple means of diverting the process air flow through the uptake bed while simultaneously directing the vacuum source to the regeneration bed. Additionally, the valve assembly is designed to allow for switching between uptake and regeneration modes with only one moving part while minimizing gas volume losses to the vacuum source by means of an internal pressure equalization step during actuation. The process can be controlled by a compact, low-power controller design with several modes of operation available to the user. Together with NASA Johnson Space Center, Hamilton Sundstrand Space Systems International, Inc. has been developing RCA 2.0 based on performance and design feedback on several sorbent bed test articles and valve design concepts. A final design of RCA 2.0 was selected in November 2011 and fabricated and assembled between March and August 2012, with delivery to NASA Johnson Space Center in September 2012. This paper provides an overview of the RCA system design and results of pre-delivery testing.

Uptake of Tailored Text Message Smoking Cessation Support in Pregnancy When Advertised on the Internet (MiQuit): Observational Study.

PubMed

Emery, Joanne L; Coleman, Tim; Sutton, Stephen; Cooper, Sue; Leonardi-Bee, Jo; Jones, Matthew; Naughton, Felix

2018-04-19

Smoking in pregnancy is a major public health concern. Pregnant smokers are particularly difficult to reach, with low uptake of support options and few effective interventions. Text message-based self-help is a promising, low-cost intervention for this population, but its real-world uptake is largely unknown. The objective of this study was to explore the uptake and cost-effectiveness of a tailored, theory-guided, text message intervention for pregnant smokers ("MiQuit") when advertised on the internet. Links to a website providing MiQuit initiation information (texting a short code) were advertised on a cost-per-click basis on 2 websites (Google Search and Facebook; £1000 budget each) and free of charge within smoking-in-pregnancy webpages on 2 noncommercial websites (National Childbirth Trust and NHS Choices). Daily budgets were capped to allow the Google and Facebook adverts to run for 1 and 3 months, respectively. We recorded the number of times adverts were shown and clicked on, the number of MiQuit initiations, the characteristics of those initiating MiQuit, and whether support was discontinued prematurely. For the commercial adverts, we calculated the cost per initiation and, using quit rates obtained from an earlier clinical trial, estimated the cost per additional quitter. With equal capped budgets, there were 812 and 1889 advert clicks to the MiQuit website from Google (search-based) and Facebook (banner) adverts, respectively. MiQuit was initiated by 5.2% (42/812) of those clicking via Google (95% CI 3.9%-6.9%) and 2.22% (42/1889) of those clicking via Facebook (95% CI 1.65%-2.99%). Adverts on noncommercial webpages generated 53 clicks over 6 months, with 9 initiations (9/53, 17%; 95% CI 9%-30%). For the commercial websites combined, mean cost per initiation was £24.73; estimated cost per additional quitter, including text delivery costs, was £735.86 (95% CI £227.66-£5223.93). Those initiating MiQuit via Google were typically very early in pregnancy (median gestation 5 weeks, interquartile range 10 weeks); those initiating via Facebook were distributed more evenly across pregnancy (median gestation 16 weeks, interquartile range 14 weeks). Commercial online adverts are a feasible, likely cost-effective method for engaging pregnant smokers in digital cessation support and may generate uptake at a faster rate than noncommercial websites. As a strategy for implementing MiQuit, online advertising has large reach potential and can offer support to a hard-to-reach population of smokers. ©Joanne L Emery, Tim Coleman, Stephen Sutton, Sue Cooper, Jo Leonardi-Bee, Matthew Jones, Felix Naughton. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.04.2018.

Uptake of Tailored Text Message Smoking Cessation Support in Pregnancy When Advertised on the Internet (MiQuit): Observational Study

PubMed Central

Coleman, Tim; Sutton, Stephen; Cooper, Sue; Leonardi-Bee, Jo; Jones, Matthew; Naughton, Felix

2018-01-01

Background Smoking in pregnancy is a major public health concern. Pregnant smokers are particularly difficult to reach, with low uptake of support options and few effective interventions. Text message–based self-help is a promising, low-cost intervention for this population, but its real-world uptake is largely unknown. Objective The objective of this study was to explore the uptake and cost-effectiveness of a tailored, theory-guided, text message intervention for pregnant smokers (“MiQuit”) when advertised on the internet. Methods Links to a website providing MiQuit initiation information (texting a short code) were advertised on a cost-per-click basis on 2 websites (Google Search and Facebook; £1000 budget each) and free of charge within smoking-in-pregnancy webpages on 2 noncommercial websites (National Childbirth Trust and NHS Choices). Daily budgets were capped to allow the Google and Facebook adverts to run for 1 and 3 months, respectively. We recorded the number of times adverts were shown and clicked on, the number of MiQuit initiations, the characteristics of those initiating MiQuit, and whether support was discontinued prematurely. For the commercial adverts, we calculated the cost per initiation and, using quit rates obtained from an earlier clinical trial, estimated the cost per additional quitter. Results With equal capped budgets, there were 812 and 1889 advert clicks to the MiQuit website from Google (search-based) and Facebook (banner) adverts, respectively. MiQuit was initiated by 5.2% (42/812) of those clicking via Google (95% CI 3.9%-6.9%) and 2.22% (42/1889) of those clicking via Facebook (95% CI 1.65%-2.99%). Adverts on noncommercial webpages generated 53 clicks over 6 months, with 9 initiations (9/53, 17%; 95% CI 9%-30%). For the commercial websites combined, mean cost per initiation was £24.73; estimated cost per additional quitter, including text delivery costs, was £735.86 (95% CI £227.66-£5223.93). Those initiating MiQuit via Google were typically very early in pregnancy (median gestation 5 weeks, interquartile range 10 weeks); those initiating via Facebook were distributed more evenly across pregnancy (median gestation 16 weeks, interquartile range 14 weeks). Conclusions Commercial online adverts are a feasible, likely cost-effective method for engaging pregnant smokers in digital cessation support and may generate uptake at a faster rate than noncommercial websites. As a strategy for implementing MiQuit, online advertising has large reach potential and can offer support to a hard-to-reach population of smokers. PMID:29674308

Uptake of Nickel by Synthetic Mackinawite

EPA Science Inventory

The uptake of aqueous Ni(II) by synthetic mackinawite (FeS) was examined in anaerobic batch experiments at near-neutral pH (5.2 to 8.4). Initial molar ratios of Ni(II) to FeS ranged from 0.008 to 0.83 and maximum Ni concentrations in mackinawite, expressed as the cation mol fract...

The impact of the Baby Friendly Health Initiative in the Australian health care system: a critical narrative review of the evidence.

PubMed

Atchan, Marjorie; Davis, Deborah; Foureur, Maralyn

2013-07-01

Studies have identified that the practices of maternity facilities and health professionals are crucial to women's experience of support and breastfeeding 'success'. The Baby Friendly Hospital Initiative (BFHI) was launched globally in 1991 to protect, promote and support breastfeeding. While a direct causal effect has not been established and critics suggest the rhetoric conflicts with women's lived experiences as new mothers, a positive association between the Initiative and breastfeeding prevalence is apparent. Internationally, impact studies have demonstrated that where the Initiative is well integrated, there is an increase in rates of breastfeeding initiation and, to a lesser extent, duration. In consideration of the known health risks associated with the use of artificial baby milks this would suggest that BFHI implementation and accreditation should be a desirable strategy for committed health facilities. However, a variation in both BFHI uptake and breastfeeding prevalence between nations has been reported. This narrative review critically discusses a variety of issues relevant to the uptake and support of breastfeeding and the BFHI, utilising Australia as a case study. Whilst it enjoys 'in principle' policy support, Australia also suffers from a lack of uniformity in uptake and perception of the benefits of BFHI at all levels of the health system. Australian and international studies have identified similar enablers and barriers to implementation.

Assessing university students' sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior.

PubMed

Rohde, Rebecca L; Adjei Boakye, Eric; Christopher, Kara M; Geneus, Christian J; Walker, Ronald J; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-06-14

There exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population. Data (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19-26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion. A significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion. HPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18-26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vivo fate of 125I SS-B (La) injected into mice.

PubMed Central

Schrieber, L; Erhardt, C C; Melsom, R D; Venables, P J; McCarthy, D A; Mumford, P A; Horsfall, A C; Maini, R N

1983-01-01

The fate of the radiolabelled soluble cellular antigen SS-B (La) was compared with that of other 125I-labelled proteins of known molecular weight (MW) and electrostatic charge, following i.v. injection into BALB/c mice. The plasma half-life of 125I-SS-B was 3 min, while that of 125I-bovine serum albumin (similar MW and electrostatic charge) was 270 min. 125I-heat-aggregated IgG (MW greater than 1 x 10(6)) and 125I-7S human IgG (MW 168,000) had plasma half-lives of 40 min and greater than 300 min, respectively. Liver and kidney showed preferential uptake of 125I-SS-B, followed by a rapid decrease in radioactivity. During this time low MW, trichloroacetic acid (TCA) soluble, material appeared in urine. This suggests a specific uptake mechanism followed by a catabolic phase. These studies demonstrate that normal mice remove 125I-SS-B rapidly from the circulation and then degrade it. This rapid antigen elimination may protect against the induction of potentially harmful autoantibody responses. PMID:6832805

Measurement and modeling of polychlorinated biphenyl bioaccumulation from sediment for the marine polychaete neanthes arenaceodentata and response to sorbent amendment

USGS Publications Warehouse

Janssen, E.M.-L.; Croteau, M.-N.; Luoma, S.N.; Luthy, R.G.

2010-01-01

Bioaccumulation rates of polychlorinated biphenyls (PCBs) for the marine polychaete Neanthes arenaceodentata were characterized, including PCB uptake rates from water and sediment, and the effect of sorbent amendment to the sediment on PCB bioavailability, organism growth, and lipid content. Physiological parameters were incorporated into a biodynamic model to predict contaminant uptake. The results indicate rapid PCB uptake from contaminated sediment and significant organism growth dilution during time-series exposure studies. PCB uptake from the aqueous phase accounted for less than 3% of the total uptake for this deposit-feeder. Proportional increase of gut residence time and assimilation efficiency as a consequence of the organism's growth was assessed by PCB uptake and a reactor theory model of gut architecture. Pulse-chase feeding and multilabeled stable isotope tracing techniques proved high sediment ingestion rates (i.e., 6?10 times of dry body weight per day) indicating that such deposit-feeders are promising biological indicators for sediment risk assessment. Activated carbon amendment reduced PCB uptake by 95% in laboratory experiments with no observed adverse growth effects on the marine polychaete. Biodynamic modeling explained the observed PCB body burdens for N. arenaceodentata, with and without sorbent amendment. ?? 2009 American Chemical Society.

Designing a rapid response program to support evidence-informed decision-making in the Americas region: using the best available evidence and case studies.

PubMed

Haby, Michelle M; Chapman, Evelina; Clark, Rachel; Barreto, Jorge; Reveiz, Ludovic; Lavis, John N

2016-08-18

The objective of this work was to inform the design of a rapid response program to support evidence-informed decision-making in health policy and practice for the Americas region. Specifically, we focus on the following: (1) What are the best methodological approaches for rapid reviews of the research evidence? (2) What other strategies are needed to facilitate evidence-informed decision-making in health policy and practice? and (3) How best to operationalize a rapid response program? The evidence used to inform the design of a rapid response program included (i) two rapid reviews of methodological approaches for rapid reviews of the research evidence and strategies to facilitate evidence-informed decision-making, (ii) supplementary literature in relation to the "shortcuts" that could be considered to reduce the time needed to complete rapid reviews, (iii) four case studies, and (iv) supplementary literature to identify additional operational issues for the design of the program. There is no agreed definition of rapid reviews in the literature and no agreed methodology for conducting them. Better reporting of rapid review methods is needed. The literature found in relation to shortcuts will be helpful in choosing shortcuts that maximize timeliness while minimizing the impact on quality. Evidence for other strategies that can be used concurrently to facilitate the uptake of research evidence, including evidence drawn from rapid reviews, is presented. Operational issues that need to be considered in designing a rapid response program include the implications of a "user-pays" model, the importance of recruiting staff with the right mix of skills and qualifications, and ensuring that the impact of the model on research use in decision-making is formally evaluated. When designing a new rapid response program, greater attention needs to be given to specifying the rapid review methods and reporting these in sufficient detail to allow a quality assessment. It will also be important to engage in other strategies to facilitate the uptake of the rapid reviews and to evaluate the chosen model in order to make refinements and add to the evidence base for evidence-informed decision-making.

Electroneutral, HCO3(-)-independent, pH gradient-dependent uphill transport of Cl- by ileal brush-border membrane vesicles. Possible role in the pathogenesis of chloridorrhea.

PubMed Central

Vasseur, M; Caüzac, M; Alvarado, F

1989-01-01

By applying a rapid filtration technique to isolated brush border membrane vesicles from guinea pig ileum, 36Cl uptake was quantified in the presence and absence of electrical, pH and alkali-metal ion gradients. A mixture of 20 mM-Hepes and 40 mM-citric acid, adjusted to the desired pH with Tris base, was found to be the most suitable buffer. Malate and Mes could be used to replace the citrate, but succinate, acetate and maleate proved to be unsuitable. In the absence of a pH gradient (pHout:pHin = 7.5:7.5), Cl- uptake increased slightly when an inside-positive membrane potential was applied, but uphill transport was never observed. A pH gradient (pHout:pHin = 5.0:7.5) induced both a 400% increase in the initial Cl- influx rate and a long-lasting (20 to 300 s) overshoot, indicating that a proton gradient can furnish the driving force for uphill Cl- transport. Under pH gradient conditions, initial Cl- entry rates had the following characteristics. (1) They were unaffected by cis-Na+ and/or -K+, indicating the absence of Cl-/K+, Cl-/Na+ or Cl-/K+/Na+ symport activity. (2) Inhibition by 20-100 mM-trans-Na+ and/or -K+ occurred, independent of the existence of an ion gradient. (3) Cl- entry was practically unaffected by short-circuiting the membrane potential with equilibrated potassium and valinomycin. (4) Carbonyl cyanide m-chlorophenylhydrazone was strongly inhibitory and so, to a lesser extent, was 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid [(SITS)], independent of the sign and size of the membrane potential. (5) Cl- entry was negligibly increased (less than 30%) by either trans-Cl- or -HCO3-, indicating the absence of an obligatory Cl-/anion antiport activity. In contrast, the height of the overshoot at 60 s was increased by trans-Cl-, indicating time-dependent inhibition of 36Cl efflux. That competitive inhibition of 36Cl fluxes by anions is involved here is supported by initial influx rate experiments demonstrating: (1) the saturability of Cl- influx, which was found to exhibit Michaelis-Menten kinetics; and (2) competitive inhibition of influx by cis-Cl- and -Br-. Quantitatively, the conclusion is warranted that over 85% of the total initial Cl- uptake energized by a pH gradient involves an electroneutral Cl-/H+ symporter or its physicochemical equivalent, a Cl-/OH- antiporter, exhibiting little Cl- uniport and either Cl-/Cl- or Cl-/HCO3- antiport activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2597129

Seasonal influenza vaccination delivery through community pharmacists in England: evaluation of the London pilot

PubMed Central

Atkins, Katherine; van Hoek, Albert Jan; Watson, Conall; Baguelin, Marc; Choga, Lethiwe; Patel, Anika; Raj, Thara; Jit, Mark; Griffiths, Ulla

2016-01-01

Objective To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies. Design We analysed 2013–2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011–2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme. Setting All London boroughs. Participants London-based GPs, and pharmacies that currently offer seasonal flu vaccination. Interventions Not applicable. Main outcome measures Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative. Results No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to £2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data. Conclusions Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data. PMID:26883237

Seasonal influenza vaccination delivery through community pharmacists in England: evaluation of the London pilot.

PubMed

Atkins, Katherine; van Hoek, Albert Jan; Watson, Conall; Baguelin, Marc; Choga, Lethiwe; Patel, Anika; Raj, Thara; Jit, Mark; Griffiths, Ulla

2016-02-16

To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies. We analysed 2013-2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011-2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme. All London boroughs. London-based GPs, and pharmacies that currently offer seasonal flu vaccination. Not applicable. Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative. No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to £2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data. Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Investigations of the mechanism of vitamin E removal from blood and the effect of NO/sub 2/ on the pulmonary uptake of vitamin E

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

Gardner, H.K.

1987-01-01

To examine the effect of NO/sub 2/ on vitamin E uptake by lung, we first investigated the mechanism of removal of vitamin E from blood. To accomplish this, a method for labeling serum with tritiated vitamin E was developed. Two other lipids, whose uptake is better understood, were also studied, and compared with vitamin E. Tritiated triacylglycerol was used to monitor lipoprotein lipase-mediated uptake, while tritiated cholesterol was used to monitor LDL receptor-mediated uptake. Blood curves derived from untreated, adult, male, Long-Evans rats indicated that all three lipids were removed biexponentially. The half-life for the Rapid component was 2.5-3.7 minutesmore » for all lipids. The slower curve had half-lives of 42.3 minutes for triacylglycerol, 990.0 minutes for cholesterol, and 288.8 minutes for vitamin E. Biological screening of labeled serum demonstrated that the faster process was not simply the removal of lipoproteins damaged by the labeling process. Hepatectomy affected the rate of neither triacylglycerol nor cholesterol removal, but did slow vitamin E uptake, suggesting a distinct role for liver in vitamin E extraction.« less

Pulmonary uptake of morphine (M)

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

Roerig, D.L.; Bunke, S.S.; Kotrly, K.J.

Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H/sub 2/O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium withinmore » 4 min. At equilibrium lung/perfusate conc. ratios for H/sub 2/O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H/sub 2/O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H/sub 2/O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs.« less

In vitro and in vivo evaluation of new radiolabeled neurotensin(8-13) analogues with high affinity for NT1 receptors.

PubMed

García-Garayoa, E; Allemann-Tannahill, L; Bläuenstein, P; Willmann, M; Carrel-Rémy, N; Tourwé, D; Iterbeke, K; Conrath, P; Schubiger, P A

2001-01-01

The potential utility of neurotensin (NT) in cancer diagnosis and therapy is limited by its rapid degradation. New stabilized analogues were synthesized, labeled with [99mTc] and screened in vitro and in vivo. High affinity and rapid internalization were obtained in binding assays. Despite their longer human plasma half-lives, a rapid degradation was observed with low concentrations as used in biodistribution tests. The tumor uptake rates were rather low but tumor/blood ratios increased according to the stability raise.

Extracellular enzymes facilitate electron uptake in biocorrosion and bioelectrosynthesis.

PubMed

Deutzmann, Jörg S; Sahin, Merve; Spormann, Alfred M

2015-04-21

Direct, mediator-free transfer of electrons between a microbial cell and a solid phase in its surrounding environment has been suggested to be a widespread and ecologically significant process. The high rates of microbial electron uptake observed during microbially influenced corrosion of iron [Fe(0)] and during microbial electrosynthesis have been considered support for a direct electron uptake in these microbial processes. However, the underlying molecular mechanisms of direct electron uptake are unknown. We investigated the electron uptake characteristics of the Fe(0)-corroding and electromethanogenic archaeon Methanococcus maripaludis and discovered that free, surface-associated redox enzymes, such as hydrogenases and presumably formate dehydrogenases, are sufficient to mediate an apparent direct electron uptake. In genetic and biochemical experiments, we showed that these enzymes, which are released from cells during routine culturing, catalyze the formation of H2 or formate when sorbed to an appropriate redox-active surface. These low-molecular-weight products are rapidly consumed by M. maripaludis cells when present, thereby preventing their accumulation to any appreciable or even detectable level. Rates of H2 and formate formation by cell-free spent culture medium were sufficient to explain the observed rates of methane formation from Fe(0) and cathode-derived electrons by wild-type M. maripaludis as well as by a mutant strain carrying deletions in all catabolic hydrogenases. Our data collectively show that cell-derived free enzymes can mimic direct extracellular electron transfer during Fe(0) corrosion and microbial electrosynthesis and may represent an ecologically important but so far overlooked mechanism in biological electron transfer. The intriguing trait of some microbial organisms to engage in direct electron transfer is thought to be widespread in nature. Consequently, direct uptake of electrons into microbial cells from solid surfaces is assumed to have a significant impact not only on fundamental microbial and biogeochemical processes but also on applied bioelectrochemical systems, such as microbial electrosynthesis and biocorrosion. This study provides a simple mechanistic explanation for frequently observed fast electron uptake kinetics in microbiological systems without a direct transfer: free, cell-derived enzymes can interact with cathodic surfaces and catalyze the formation of intermediates that are rapidly consumed by microbial cells. This electron transfer mechanism likely plays a significant role in various microbial electron transfer reactions in the environment. Copyright © 2015 Deutzmann et al.

Luminal and systemic signals trigger intestinal adaptation in the juvenile python.

PubMed

Secor, S M; Whang, E E; Lane, J S; Ashley, S W; Diamond, J

2000-12-01

Juvenile pythons undergo large rapid upregulation of intestinal mass and intestinal transporter activities upon feeding. Because it is also easy to do surgery on pythons and to maintain them in the laboratory, we used a python model to examine signals and agents for intestinal adaptation. We surgically isolated the middle third of the small intestine from enteric continuity, leaving its mesenteric nerve and vascular supply intact. Intestinal continuity was restored by an end-to-end anastomosis between the proximal and distal thirds. Within 24 h of the snake's feeding, the reanastomosed proximal and distal segments (receiving luminal nutrients) had upregulated amino acid and glucose uptakes by up to 15-fold, had doubled intestinal mass, and thereby soon achieved total nutrient uptake capacities equal to those of the normal fed full-length intestine. At this time, however, the isolated middle segment, receiving no luminal nutrients, experienced no changes from the fasted state in either nutrient uptakes or in morphology. By 3 days postfeeding, the isolated middle segment had upregulated nutrient uptakes to the same levels as the reanastomosed proximal and distal segments, but it still lacked any appreciable morphological response. These contrasting results for the reanastomosed intestine and for the isolated middle segment suggest that luminal nutrients and/or pancreatic biliary secretions are the agents triggering rapid upregulation of transporters and of intestinal mass and that systemic nerve or hormonal signals later trigger transporter regulation but no trophic response.

Design of a Highly Specific And Noninvasive Biosensor Suitable for Real-Time in Vivo Imaging of Mercury (II) Uptake

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

Chapleau, R.R.; Blomberg, R.; Ford, P.C.

2009-05-12

Mercury is a ubiquitous pollutant that when absorbed is extremely toxic to a wide variety of biochemical processes. Mercury (II) is a strong, invisible poison that is rapidly absorbed by tissues of the intestinal tract, kidneys, and liver upon ingestion. In this study, a novel fluorescence-based biosensor is presented that allows for the direct monitoring of the uptake and distribution of the metal under noninvasive in vivo conditions. With the introduction of a cysteine residue at position 205, located in close proximity to the chromophore, the green fluorescent protein (GFP) from Aequorea victoria was converted into a highly specific biosensormore » for this metal ion. The mutant protein exhibits a dramatic absorbance and fluorescence change upon mercuration at neutral pH. Absorbance and fluorescence properties with respect to the metal concentration exhibit sigmoidal binding behavior with a detection limit in the low nanomolar range. Time-resolved binding studies indicate rapid subsecond binding of the metal to the protein. The crystal structures obtained of mutant eGFP205C indicate a possible access route of the metal into the core of the protein. To our knowledge, this engineered protein is a first example of a biosensor that allows for noninvasive and real-time imaging of mercury uptake in a living cell. A major advantage is that its expression can be genetically controlled in many organisms to enable unprecedented studies of tissue specific mercury uptake.« less

Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen.

PubMed

Zhu, Haiyan; Fang, Xiaoyun; Zhang, Dongmei; Wu, Weicheng; Shao, Miaomiao; Wang, Lan; Gu, Jianxin

2016-01-01

Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β as well as DC maturation by the evaluation of CD80 and CD86 expression. On the other hand, Hsp60, Hsp70 and Hsp90 on cells could facilitate the uptake of dying cells by bone marrow-derived dendritic cells. Lectin-like oxidized LDL receptor-1 (LOX-1), as a common receptor for Hsp60, Hsp70, and Hsp90, is response for their recognition and mediates the uptake of dying cells. Furthermore, membrane-bound Hsp60, Hsp70 and Hsp90 could promote the cross-presentation of OVA antigen from E.G7 cells and inhibition of the uptake of dying cells by LOX-1 decreases the cross-presentation of cellular antigen. Therefore, the rapid exposure of HSPs on dying cells at the early stage allows for the recognition by and confers an activation signal to the immune system.

Uptake and effects of 2, 4, 6 - trinitrotoluene (TNT) in juvenile Atlantic salmon (Salmo salar).

PubMed

Mariussen, Espen; Stornes, Siv Marie; Bøifot, Kari Oline; Rosseland, Bjørn Olav; Salbu, Brit; Heier, Lene Sørlie

2018-01-01

Organ specific uptake and depuration, and biological effects in Atlantic salmon (Salmo salar) exposed to 2, 4, 6-trinitrotoluene (TNT) were studied. Two experiments were conducted, the first using radiolabeled TNT ( 14 C-TNT, 0.16mg/L) to study uptake (48h) and depuration (48h), while the second experiment focused on physiological effects in fish exposed to increasing concentrations of unlabeled TNT (1μg-1mg/L) for 48h. The uptake of 14 C-TNT in the gills and most of the organs increased rapidly during the first 6h of exposure (12h in the brain) followed by a rapid decrease even though the fish were still exposed to TNT in the water. The radioactivity in the gall bladder reached a maximum after 55h, 7h after the transfer to the clean water. A high concentration of 14 C-TNT in the gall bladder indicates that TNT is excreted through the gall bladder. Mortality (2 out of 14) was observed at a concentration of 1mg/L, and the surviving fish had hemorrhages in the dorsal muscle tissue near the spine. Analysis of the physiological parameters in blood from the high exposure group revealed severe effects, with an increase in the levels of glucose, urea and HCO 3 , and a decrease in hematocrit and the levels of Cl and hemoglobin. No effects on blood physiology were observed in fish exposed to the lower concentrations of TNT (1-100μg/L). TNT and the metabolites 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT) were found in the muscle tissue, whereas only 2-ADNT and 4-ADNT were found in the bile. The rapid excretion and estimated bioconcentration factors (range of 2-18 after 48h in gills, blood, liver, kidney, muscle and brain) indicated a low potential for bioaccumulation of TNT. Copyright © 2017 Elsevier B.V. All rights reserved.

The Genesis, Implementation and Impact of the Better Access Mental Health Initiative Introducing Medicare-Funded Psychology Services

ERIC Educational Resources Information Center

Littlefield, Lyn; Giese, Jill

2008-01-01

The Australian Government's Better Access to Mental Health Care initiative introduced mental health reforms that included the availability of Medicare-funded psychology services. The mental health initiative has resulted in a huge uptake of these services, demonstrating the strong community demand for psychological treatment. The initiative has…

Revision of gonadal radiation dose to man from thallium-201

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

Hosain, P.; Hosain, F.

1981-06-01

Thallium-201 as thallous chloride is now routinely used for myocardial imaging. We observed a biological translocation of T1-201 leading to a gradual increase in the concentration of radioactivity in the testes which facilitated testicular imaging. The initial distribution of intravenously injected tracer dose is greatly dependent on the distribution of cardiac output, but its metabolic fate is analogous to the potassium ion. We have extensively studied the kinetics of thallium in rats, and also carried out limited comparative studies in different species. An attempt was also made to compare the uptake values that could be obtained in dogs by quantitativemore » imaging and by autopsy. Separation of scrotum, epididymis and testes revealed that the increase in uptake occurred predominantly in the testes. The uptake increased with time for about 1 day, and after 2 days it declined with a biological half-life of approximately 2 days. The later phase of testicular clearance was similar to the rate of clearance from other organs. The testicular uptake of T1-201 was highest in rats: the initial value at 10 to 15 min was 0.48 +- 0.09% of the injected dose which increased to 1.77 +- 0.20% by 1 day. The initial uptake in mice was low (0.18 +- 0.06%) but it increased to about 4 folds by 1 day. Values in human, extrapolated from limited quantitative imaging, was similar to mice. These studies indicated the need for the revision of the gonadal radiation dose to man. Calculations show, contrary to the accepted value of about 0.5 rads/mCi, an approximate value of 1.5 rads/mCi is more realistic.« less

Distance from household to clinic and its association with the uptake of prevention of mother-to-child HIV transmission regimens in rural Zambia

PubMed Central

Escamilla, Veronica; Chibwesha, Carla J.; Gartland, Matthew; Chintu, Namwinga; Mubiana-Mbewe, Mwangelwa; Musokotwane, Kebby; Musonda, Patrick; Miller, William C.; Stringer, Jeffrey S. A.; Chi, Benjamin H.

2016-01-01

Background In rural settings, HIV-infected pregnant women often live significant distances from facilities that provide prevention of mother-to-child transmission (PMTCT) services. Methods We implemented a pilot project to offer universal maternal combination antiretroviral regimens in 4 clinics in rural Zambia. To evaluate the impact of services, we conducted a household survey in communities surrounding each facility. We collected information about HIV status and antenatal service utilization from women who delivered in the past two years. Using household global positing systems coordinates collected in the survey, we measured Euclidean (i.e., straight line) distance between individual households and clinics. Multivariable logistic regression and predicted probabilities were used to determine associations between distance and uptake of any PMTCT regimen and combination antiretroviral regimens specifically. Results From March to December 2011, 390 HIV-infected mothers were surveyed across four communities. Of these, 254 (65%) had household geographical coordinates documented. 168 women reported use of a PMTCT regimen during pregnancy, including 102 who initiated a combination antiretroviral regimen. The probability of PMTCT regimen initiation was highest within 1.9 km of the facility and gradually declined. Overall, 103 of 145 (71%) who lived within 1.9 km of the facility initiated PMTCT, versus 65 of 109 (60%) who lived farther away. For every kilometer increase, the association with PMTCT regimen uptake (adjusted odds ratio [AOR]: 0.90, 95%CI: 0.82—0.99) and combination antiretroviral regimen uptake (AOR: 0.88, 95%CI: 0.80—0.97) decreased. Conclusions In this rural African setting, uptake of PMTCT regimens was influenced by distance to health facility. Program models that further decentralize care into remote communities are urgently needed. PMID:26470035

A systematic review of qualitative findings on factors enabling and deterring uptake of HIV testing in Sub-Saharan Africa

PubMed Central

2013-01-01

Background Despite Sub-Saharan Africa (SSA) being the epicenter of the HIV epidemic, uptake of HIV testing is not optimal. While qualitative studies have been undertaken to investigate factors influencing uptake of HIV testing, systematic reviews to provide a more comprehensive understanding are lacking. Methods Using Noblit and Hare’s meta-ethnography method, we synthesised published qualitative research to understand factors enabling and deterring uptake of HIV testing in SSA. We identified 5,686 citations out of which 56 were selected for full text review and synthesised 42 papers from 13 countries using Malpass’ notion of first-, second-, and third-order constructs. Results The predominant factors enabling uptake of HIV testing are deterioration of physical health and/or death of sexual partner or child. The roll-out of various HIV testing initiatives such as ‘opt-out’ provider-initiated HIV testing and mobile HIV testing has improved uptake of HIV testing by being conveniently available and attenuating fear of HIV-related stigma and financial costs. Other enabling factors are availability of treatment and social network influence and support. Major barriers to uptake of HIV testing comprise perceived low risk of HIV infection, perceived health workers’ inability to maintain confidentiality and fear of HIV-related stigma. While the increasingly wider availability of life-saving treatment in SSA is an incentive to test, the perceived psychological burden of living with HIV inhibits uptake of HIV testing. Other barriers are direct and indirect financial costs of accessing HIV testing, and gender inequality which undermines women’s decision making autonomy about HIV testing. Despite differences across SSA, the findings suggest comparable factors influencing HIV testing. Conclusions Improving uptake of HIV testing requires addressing perception of low risk of HIV infection and perceived inability to live with HIV. There is also a need to continue addressing HIV-related stigma, which is intricately linked to individual economic support. Building confidence in the health system through improving delivery of health care and scaling up HIV testing strategies that attenuate social and economic costs of seeking HIV testing could also contribute towards increasing uptake of HIV testing in SSA. PMID:23497196

Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid and surfactant protein expression.

PubMed

Torday, John; Rehan, Virender

2011-08-01

Adipocyte differentiation-related protein (ADRP) is a critically important protein that mediates lipid uptake, and is highly expressed in lung lipofibroblasts (LIFs). Triacylglycerol secreted from the pulmonary circulation and stored in lipid storage droplets is a robust hormonal-, growth factor-, and stretch-regulated precursor for surfactant phospholipid synthesis by alveolar type II epithelial (ATII) cells. A549 lung epithelial cells rapidly take up green fluorescent protein (GFP)-ADRP fusion protein-associated lipid droplets (LDs) in a dose-dependent manner. The LDs initially localize to the perinuclear region of the cell, followed by localization in the cytoplasm. Uptake of ADRP-LDs causes a time- and dose-dependent increase in surfactant protein-B (SP-B) expression. This mechanism can be inhibited by either actinomycin D or cycloheximide, indicating that ADRP-LDs induce newly synthesized SP-B. ADRP-LDs concomitantly stimulate saturated phosphatidylcholine (satPC) synthesis by A549 cells, which is inhibited by ADRP antibody, indicating that this is a receptor-mediated mechanism. Intravenous administration of GFP-ADRP LDs to adult rats results in dose-dependent increases in lung ADRP and SP-B expression. These data indicate that lipofibroblast-derived ADRP coordinates ATII cells' synthesis of the surfactant phospholipid-protein complex by stimulating both satPC and SP-B. The authors propose, therefore, that ADRP is the physiologic determinant for the elusive coordinated, stoichiometric synthesis of surfactant phospholipid and protein by pulmonary ATII cells.

Gas-Phase Dopant-Induced Conformational Changes Monitored with Transversal Modulation Ion Mobility Spectrometry.

PubMed

Meyer, Nicole Andrea; Root, Katharina; Zenobi, Renato; Vidal-de-Miguel, Guillermo

2016-02-16

The potential of a Transversal Modulation Ion Mobility Spectrometry (TMIMS) instrument for protein analysis applications has been evaluated. The Collision Cross Section (CCS) of cytochrome c measured with the TMIMS is in agreement with values reported in the literature. Additionally, it enables tandem IMS-IMS prefiltration in dry gas and in vapor doped gas. The chemical specificity of the different dopants enables interesting studies on the structure of proteins as CCS changed strongly depending on the specific dopant. Hexane produced an unexpectedly high CCS shift, which can be utilized to evaluate the exposure of hydrophobic parts of the protein. Alcohols produced higher shifts with a dual behavior: an increase in CCS due to vapor uptake at specific absorption sites, followed by a linear shift typical for unspecific and unstable vapor uptake. The molten globule +8 shows a very specific transition. Initially, its CCS follows the trend of the compact folded states, and then it rapidly increases to the levels of the unfolded states. This strong variation suggests that the +8 charge state undergoes a dopant-induced conformational change. Interestingly, more sterically demanding alcohols seem to unfold the protein more effectively also in the gas phase. This study shows the capabilities of the TMIMS device for protein analysis and how tandem IMS-IMS with dopants could provide better understanding of the conformational changes of proteins.

Impact of Light and Temperature on the Uptake of Algal Symbionts by Coral Juveniles

PubMed Central

Abrego, David; Willis, Bette L.; van Oppen, Madeleine J. H.

2012-01-01

The effects of temperature and light on the breakdown of the coral-Symbiodinium symbiosis are well documented but current understanding of their roles during initial uptake and establishment of symbiosis is limited. In this study, we investigate how temperature and light affect the uptake of the algal symbionts, ITS1 types C1 and D, by juveniles of the broadcast-spawning corals Acropora tenuis and A. millepora. Elevated temperatures had a strong negative effect on Symbiodinium uptake in both coral species, with corals at 31°C showing as little as 8% uptake compared to 87% at 28°C. Juveniles in high light treatments (390 µmol photons m−2 s−1) had lower cell counts across all temperatures, emphasizing the importance of the light environment during the initial uptake phase. The proportions of the two Symbiodinium types taken up, as quantified by a real time PCR assay using clade C- and D-specific primers, were also influenced by temperature, although variation in uptake dynamics between the two coral species indicates a host effect. At 28°C, A. tenuis juveniles were dominated by C1 Symbiodinium, and while the number of D Symbiodinium cells increased at 31°C, they never exceeded the number of C1 cells. In contrast, juveniles of A. millepora had approximately equal numbers of C1 and D cells at 28°C, but were dominated by D at 30°C and 31°C. This study highlights the significant role that environmental factors play in the establishment of coral-Symbiodinium symbiosis and provides insights into how potentially competing Symbiodinium types take up residence in coral juveniles. PMID:23185603

Uptake and Accumulation of the Herbicides Chlorsulfuron and Clopyralid in Excised Pea Root Tissue 1

PubMed Central

Devine, Malcolm D.; Bestman, Hank D.; Vanden Born, William H.

1987-01-01

The herbicides chlorsulfuron and clopyralid were taken up rapidly by excised pea root tissue and accumulated in the tissue to concentrations ten and four times those in the external medium, respectively. Uptake was related linearly to external herbicide concentration over a wide concentration range, implying that transport across the membrane is by nonfacilitated diffusion. Uptake of both compounds was influenced by pH, with greatest uptake at low pH. The pH dependence of uptake suggests that the herbicides (both of which are weak acids) are transported across the plasma membrane in the undissociated form, and accumulate in the cytoplasm by an ion trap mechanism. Most of the absorbed herbicide effluxed from the tissue when it was transferred to herbicide-free buffer, indicating that the accumulation was not due to irreversible binding. Consequently, both herbicides remain available for transfer to the phloem. These results can explain the high reported phloem mobility of clopyralid in intact plants. The low phloem mobility of chlorsulfuron must be accounted for by factors that override its ability to accumulate in the symplast. PMID:16665689

Uptake, elimination, and relative distribution of perchlorate in various tissues of channel catfish

USGS Publications Warehouse

Park, J.-W.; Bradford, C.M.; Rinchard, J.; Liu, F.; Wages, M.; Waters, A.; Kendall, R.J.; Anderson, T.A.; Theodorakis, C.W.

2007-01-01

This study was undertaken to determine the kinetics of uptake and elimination of perchlorate in channel catfish, Ictalurus punctatus. Perchlorate - an oxidizer used in solid fuel rockets, fireworks, and illuminating munitions - has been shown to effect thyroid function, causing hormone disruption and potential perturbations of metabolic activities. For the uptake study, catfish were exposed to 100 mg/L sodium perchlorate for 12 h to 5 d in the laboratory. Perchlorate in tissues was analyzed using ion chromatography. The highest perchlorate concentrations were found in the head and fillet, indicating that these tissues are the most important tissues to analyze when determining perchlorate uptake into large fish. To calculate uptake and elimination rate constants for fillet, gills, G-I tract, liver, and head, fish were exposed to 100 ppm sodium perchlorate for 5 days, and allowed to depurate in clean water for up to 20 days. The animals rapidly eliminated the perchlorate accumulated showing the highest elimination in fillet (Ke = 1.67 day -1) and lowest elimination in liver (Ke = 0.79 day -1). ?? 2007 American Chemical Society.

Spatiotemporal dynamics of soil phosphorus and crop uptake in global cropland during the 20th century

NASA Astrophysics Data System (ADS)

Zhang, Jie; Beusen, Arthur H. W.; Van Apeldoorn, Dirk F.; Mogollón, José M.; Yu, Chaoqing; Bouwman, Alexander F.

2017-04-01

Phosphorus (P) plays a vital role in global crop production and food security. In this study, we investigate the changes in soil P pool inventories calibrated from historical countrywide crop P uptake, using a 0.5-by-0.5° spatially explicit model for the period 1900-2010. Globally, the total P pool per hectare increased rapidly between 1900 and 2010 in soils of Europe (+31 %), South America (+2 %), North America (+15 %), Asia (+17 %), and Oceania (+17 %), while it has been stable in Africa. Simulated crop P uptake is influenced by both soil properties (available P and the P retention potential) and crop characteristics (maximum uptake). Until 1950, P fertilizer application had a negligible influence on crop uptake, but recently it has become a driving factor for food production in industrialized countries and a number of transition countries like Brazil, Korea, and China. This comprehensive and spatially explicit model can be used to assess how long surplus P fertilization is needed or how long depletions of built-up surplus P can continue without affecting crop yield.

HuPSON: the human physiology simulation ontology.

PubMed

Gündel, Michaela; Younesi, Erfan; Malhotra, Ashutosh; Wang, Jiali; Li, Hui; Zhang, Bijun; de Bono, Bernard; Mevissen, Heinz-Theodor; Hofmann-Apitius, Martin

2013-11-22

Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios.The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain.

Isolation and identification of Trichoderma harzianum from groundwater: An effective biosorbent for defluoridation of groundwater.

PubMed

Koshle, Shalini; Mahesh, S; Swamy, S Nanjunda

2016-01-01

The ability of non-viable form of Trichoderma harzianum, isolated from fluoride rich groundwater, was investigated as biosorbent for defluoridation of groundwater. Biosorption experiments were carried out at laboratory scale for removal of fluoride from groundwater. Significant effect of operational parameters on fluoride biosorption using Trichoderma harzianum as biosorbent was evaluated by varying operational parameters such as: initial fluoride concentration (2-8 mgl(-1)), biosorbent dose (0.4-1.6g/100ml), groundwater pH (6-10), temperature (30-50 degrees C) and biosorption time (30-120 min). The fluoride adsorption isotherms were modeled by Langmuir and Freundlich isotherms. Our result showed that fluoride biosorption, significantly increased with increase in groundwater pH, biosorbent dose, temperature and biosorption time, whereas increase in initial fluoride concentration reduced fluoride removal. The fluoride biosorption was rapid and maximum fluoride uptake was attained with 1.6g 100ml(-1) biosorbent within 60 min. Optimal pH 10 and temperature 50 degrees C gave maximum defluoridation efficiency. Freundlich isotherm fits well for defluoridation of groundwater using Trichoderma harzianum as biosorbent which indicated that biosorbent surface sites were heterogeneous in nature and fitted into heterogeneous site binding model.

Predictors of insulin uptake among adults with type 2 diabetes in the Stepping Up Study.

PubMed

Holmes-Truscott, Elizabeth; Furler, John; Blackberry, Irene; O'Neal, David N; Speight, Jane

2017-11-01

We aimed to investigate predictors of insulin uptake, and change in insulin appraisals, among adults with type 2 diabetes mellitus (T2DM) who participated in the Stepping Up trial. The Stepping Up model of care, supporting timely insulin initiation in primary care, was evaluated in a two-armed cluster-randomised controlled trial. Participants were 266 adults (mean±SD age 62±10years; 39% women) with T2DM (median (IQR) duration 8.5 (5, 13)years) from 74 primary care practices (Stepping Up intervention: 57%, control 43%). At 12months, 47% (n=126) had commenced insulin. Controlling for randomisation, logistic regression was used to explore baseline predictors of insulin uptake, including: demographic and clinical characteristics, emotional wellbeing (depressive symptoms and diabetes-related distress), insulin treatment appraisals, and, 'willingness' to initiate insulin. Two-way analysis of variance examined effects of, and interaction between, randomisation and insulin uptake on 12-month change in insulin appraisals. Participants using insulin at 12months were more likely (all p<0.05) than those with non-insulin-treated T2DM to report: lower socioeconomic status, higher baseline HbA1c (median difference: 0.3%; 3mmol/mol), greater willingness to commence insulin (very willing: 27% vs 12%), and less negative and more positive insulin appraisals. All contributed significantly to the final model (χ 2 (8)=92.1, p<0.001) except insulin appraisals. Regardless of trial allocation, those initiating insulin reported significantly greater reductions in negative insulin appraisals. Controlling for randomisation, 12-month insulin use was predicted by higher baseline HbA1c and 'willingness' to use insulin if recommended. Negative insulin appraisals reduced following insulin initiation. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of assimilable nitrogen availability in glucose uptake kinetics in Saccharomyces cerevisiae during alcoholic fermentation

PubMed Central

2012-01-01

Background The expression and activity of the different Saccharomyces cerevisiae hexose uptake systems (Hxt) and the kinetics of glucose uptake are considered essential to industrial alcoholic fermentation performance. However, the dynamics of glucose uptake kinetics during the different stages of fermentation, depending on glucose and nitrogen availability, is very poorly characterized. The objective of the present work was to examine thoroughly the alterations occurring in glucose uptake kinetics during alcoholic fermentation, by the wine strain S. cerevisiae PYCC 4072, of a synthetic grape juice basal medium with either a limiting or non-limiting initial nitrogen concentration and following nitrogen supplementation of the nitrogen-depleted sluggish fermentation. Results Independently of the initial concentration of the nitrogen source, glucose transport capacity is maximal during the early stages of fermentation and presumably sustained by the low-affinity and high-capacity glucose transporter Hxt1p. During nitrogen-limited sluggish fermentation, glucose uptake capacity was reduced to approximately 20% of its initial values (Vmax = 4.9 ± 0.8 compared to 21.9 ± 1.2 μmol h-1 10-8 cells), being presumably sustained by the low-affinity glucose transporter Hxt3p (considering the calculated Km = 39.2 ± 8.6 mM). The supplementation of the sluggish fermentation broth with ammonium led to the increase of glucose transport capacity associated to the expression of different glucose uptake systems with low and high affinities for glucose (Km = 58.2 ± 9.1 and 2.7 ± 0.4 mM). A biclustering analysis carried out using microarray data, previously obtained for this yeast strain transcriptional response to equivalent fermentation conditions, indicates that the activation of the expression of genes encoding the glucose transporters Hxt2p (during the transition period to active fermentation) and Hxt3p, Hxt4p, Hxt6p and Hxt7p (during the period of active fermentation) may have a major role in the recovery of glucose uptake rate following ammonium supplementation. These results suggest a general derepression of the glucose-repressible HXT genes and are consistent with the downregulation of Mig1p and Rgt1p. Conclusions Although reduced, glucose uptake rate during nitrogen-limited fermentation is not abrogated. Following ammonium supplementation, sluggish fermentation recovery is associated to the increase of glucose uptake capacity, related to the de novo synthesis of glucose transporters with different affinity for glucose and capacity, presumably of Hxt2p, Hxt3p, Hxt4p, Hxt6p and Hxt7p. This study is a contribution to the understanding of yeast response to different stages of alcoholic fermentation at the level of glucose uptake kinetics, in particular under nitrogen limitation or replenish, which is useful knowledge to guide fermentation practices. PMID:22846176

Utilization of ammonium as a nitrogen source: effects of ambient acidity on growth and nitrogen accumulation by soybean

NASA Technical Reports Server (NTRS)

Tolley-Henry, L.; Raper, C. D. Jr; Raper CD, J. r. (Principal Investigator)

1986-01-01

Dry matter accumulation of plants utilizing NH4+ as the sole nitrogen source generally is less than that of plants receiving NO3- unless acidity of the root-zone is controlled at a pH of about 6.0. To test the hypothesis that the reduction in growth is a consequence of nitrogen stress within the plant in response to effects of increased acidity during uptake of NH4+ by roots, nonnodulated soybean plants (Glycine max [L.] Merr. cv Ransom) were grown for 24 days in flowing nutrient culture containing 1.0 millimolar NH4+ as the nitrogen source. Acidities of the culture solutions were controlled at pH 6.1, 5.1, and 4.1 +/- 0.1 by automatic additions of 0.01 N H2SO4 or Ca(OH)2. Plants were sampled at intervals of 3 to 4 days for determination of dry matter and nitrogen accumulation. Rates of NH4+ uptake per gram root dry weight were calculated from these data. Net CO2 exchange rates per unit leaf area were measured on attached leaves by infrared gas analysis. When acidity of the culture solution was increased from pH 6.1 to 5.1, dry matter and nitrogen accumulation were reduced by about 40% within 14 days. Net CO2 exchange rates per unit leaf area, however, were not affected, and the decreased growth was associated with a reduction in rates of appearance and expansion of new leaves. The uptake rates of NH4+ per gram root were about 25% lower throughout the 24 days at pH 5.1 than at 6.1. A further increase in solution acidity from pH 5.1 to 4.1 resulted in cessation of net dry matter production and appearance of new leaves within 10 days. Net CO2 exchange rates per unit leaf area declined rapidly until all viable leaves had abscised by 18 days. Uptake rates of NH4+, which were initially about 50% lower at pH 4.1 than at 6.1 continued to decline with time of exposure until net uptake ceased at 10 days. Since these responses also are characteristic of the sequence of responses that occur during onset and progression of a nitrogen stress, they corroborate our hypothesis.

High Permeation Rates in Liposome Systems Explain Rapid Glyphosate Biodegradation Associated with Strong Isotope Fractionation.

PubMed

Ehrl, Benno N; Mogusu, Emmanuel O; Kim, Kyoungtea; Hofstetter, Heike; Pedersen, Joel A; Elsner, Martin

2018-06-19

Bacterial uptake of charged organic pollutants such as the widely used herbicide glyphosate is typically attributed to active transporters, whereas passive membrane permeation as an uptake pathway is usually neglected. For 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC) liposomes, the pH-dependent apparent membrane permeation coefficients ( P app ) of glyphosate, determined by nuclear magnetic resonance (NMR) spectroscopy, varied from P app (pH 7.0) = 3.7 (±0.3) × 10 -7 m·s -1 to P app (pH 4.1) = 4.2 (±0.1) × 10 -6 m·s -1 . The magnitude of this surprisingly rapid membrane permeation depended on glyphosate speciation and was, at circumneutral pH, in the range of polar, noncharged molecules. These findings point to passive membrane permeation as a potential uptake pathway during glyphosate biodegradation. To test this hypothesis, a Gram-negative glyphosate degrader, Ochrobactrum sp. FrEM, was isolated from glyphosate-treated soil and glyphosate permeation rates inferred from the liposome model system were compared to bacterial degradation rates. Estimated maximum permeation rates were, indeed, 2 orders of magnitude higher than degradation rates of glyphosate. In addition, biodegradation of millimolar glyphosate concentrations gave rise to pronounced carbon isotope fractionation with an apparent kinetic isotope effect, AKIE carbon , of 1.014 ± 0.003. This value lies in the range typical of non-masked enzymatic isotope fractionation demonstrating that glyphosate biodegradation was not subject to mass transfer limitations and glyphosate exchange across the cell membrane was rapid relative to enzymatic turnover.

Uptake and translocation of imidacloprid, clothianidin and flupyradifurone in seed-treated soybeans.

PubMed

Stamm, Mitchell D; Heng-Moss, Tiffany M; Baxendale, Frederick P; Siegfried, Blair D; Blankenship, Erin E; Nauen, Ralf

2016-06-01

Seed treatment insecticides have become a popular management option for early-season insect control. This study investigated the total uptake and translocation of seed-applied [(14) C]imidacloprid, [(14) C]clothianidin and [(14) C]flupyradifurone into different plant parts in three soybean vegetative stages (VC, V1 and V2). The effects of soil moisture stress on insecticide uptake and translocation were also assessed among treatments. We hypothesized that (1) uptake and translocation would be different among the insecticides owing to differences in water solubility, and (2) moisture stress would increase insecticide uptake and translocation. Uptake and translocation did not follow a clear trend in the three vegetative stages. Initially, flupyradifurone uptake was greater than clothianidin uptake in VC soybeans. In V1 soybeans, differences in uptake among the three insecticides were not apparent and unaffected by soil moisture stress. Clothianidin was negatively affected by soil moisture stress in V2 soybeans, while imidacloprid and flupyradifurone were unaffected. Specifically, soil moisture stress had a positive effect on the distribution of flupyradifurone in leaves. This was not observed with the neonicotinoids. This study enhances our understanding of the uptake and distribution of insecticides used as seed treatments in soybean. The uptake and translocation of these insecticides differed in response to soil moisture stress. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity

PubMed Central

Muñoz, Alexandra; Costa, Max

2012-01-01

Nickel (Ni) is a worldwide pollutant and contaminant that humans are exposed to through various avenues resulting in multiple toxic responses - most alarming is its clear carcinogenic nature. A variety of particulate Ni compounds persist in the environment and can be distinguished by characteristics such as solubility, structure, and surface charge. These characteristics influence cellular uptake and toxicity. Some particulate forms of Ni are carcinogenic and are directly and rapidly endocytized by cells. A series of studies conducted in the 1980’s observed this process, and we have reanalyzed the results of these studies to help elucidate the molecular mechanism of particulate Ni uptake. Originally the process of uptake observed was described as phagocytosis, however in the context of recent research we hypothesize that the process is macropinocytosis and/or clathrin mediated endocytosis. Primary considerations in determining the route of uptake here include calcium dependence, particle size, and inhibition through temperature and pharmacological approaches. Particle characteristics that influenced uptake include size, charge, surface characteristics, and structure. This discussion is relevant in the context of nanoparticle studies and the emerging interest in nano-nickel (nano-Ni), where toxicity assessments require a clear understanding of the parameters of particulate uptake and where establishment of such parameters is often obscured through inconsistencies across experimental systems. In this regard, this review aims to carefully document one system (particulate nickel compound uptake) and characterize its properties. PMID:22206756

Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity

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

Muñoz, Alexandra; Costa, Max, E-mail: Max.Costa@nyumc.org

Nickel (Ni) is a worldwide pollutant and contaminant that humans are exposed to through various avenues resulting in multiple toxic responses — most alarming is its clear carcinogenic nature. A variety of particulate Ni compounds persist in the environment and can be distinguished by characteristics such as solubility, structure, and surface charge. These characteristics influence cellular uptake and toxicity. Some particulate forms of Ni are carcinogenic and are directly and rapidly endocytized by cells. A series of studies conducted in the 1980s observed this process, and we have reanalyzed the results of these studies to help elucidate the molecular mechanismmore » of particulate Ni uptake. Originally the process of uptake observed was described as phagocytosis, however in the context of recent research we hypothesize that the process is macropinocytosis and/or clathrin mediated endocytosis. Primary considerations in determining the route of uptake here include calcium dependence, particle size, and inhibition through temperature and pharmacological approaches. Particle characteristics that influenced uptake include size, charge, surface characteristics, and structure. This discussion is relevant in the context of nanoparticle studies and the emerging interest in nano-nickel (nano-Ni), where toxicity assessments require a clear understanding of the parameters of particulate uptake and where establishment of such parameters is often obscured through inconsistencies across experimental systems. In this regard, this review aims to carefully document one system (particulate nickel compound uptake) and characterize its properties.« less

Enhanced dopamine release by dopamine transport inhibitors described by a restricted diffusion model and fast scan cyclic voltammetry

PubMed Central

Hoffman, Alexander F.; Spivak, Charles E.; Lupica, Carl R.

2016-01-01

Fast-scan cyclic voltammetry (FSCV) using carbon fiber electrodes is widely used to rapidly monitor changes in dopamine (DA) levels in vitro and in vivo. Current analytical approaches utilize parameters such as peak oxidation current amplitude and decay times to estimate release and uptake processes, respectively. However, peak amplitude changes are often observed with uptake inhibitors, thereby confounding the interpretation of these parameters. To overcome this limitation, we demonstrate that a simple, 5 parameter, two compartment model mathematically describes DA signals as a balance of release (r/ke) and uptake (ku), summed with adsorption (kads and kdes) of DA to the carbon electrode surface. Using non-linear regression, we demonstrate that our model precisely describes measured DA signals obtained in brain slice recordings. The parameters extracted from these curves were then validated using pharmacological manipulations that selectively alter vesicular release or DA transporter (DAT)-mediated uptake. Manipulation of DA release through altered Ca2+/Mg2+ ratio or tetrodotoxin (TTX), reduced the release parameter with no effect on the uptake parameter. The DAT inhibitors methylenedioxypyrovalerone (MDPV), cocaine, and nomifensine significantly reduced uptake and increased vesicular DA release. In contrast, a low concentration of amphetamine reduced uptake but had no effect on DA release. Finally, the kappa-opioid receptor (KOR) agonist U50,488 significantly reduced vesicular DA release but had no effect on uptake. Together, these data demonstrate a novel analytical approach to distinguish the effects of manipulations on DA release or uptake that can be used to interpret FSCV data. PMID:27018734

Enhanced Dopamine Release by Dopamine Transport Inhibitors Described by a Restricted Diffusion Model and Fast-Scan Cyclic Voltammetry.

PubMed

Hoffman, Alexander F; Spivak, Charles E; Lupica, Carl R

2016-06-15

Fast-scan cyclic voltammetry (FSCV) using carbon fiber electrodes is widely used to rapidly monitor changes in dopamine (DA) levels in vitro and in vivo. Current analytical approaches utilize parameters such as peak oxidation current amplitude and decay times to estimate release and uptake processes, respectively. However, peak amplitude changes are often observed with uptake inhibitors, thereby confounding the interpretation of these parameters. To overcome this limitation, we demonstrate that a simple five-parameter, two-compartment model mathematically describes DA signals as a balance of release (r/ke) and uptake (ku), summed with adsorption (kads and kdes) of DA to the carbon electrode surface. Using nonlinear regression, we demonstrate that our model precisely describes measured DA signals obtained in brain slice recordings. The parameters extracted from these curves were then validated using pharmacological manipulations that selectively alter vesicular release or DA transporter (DAT)-mediated uptake. Manipulation of DA release through altering the Ca(2+)/Mg(2+) ratio or adding tetrodotoxin reduced the release parameter with no effect on the uptake parameter. DAT inhibitors methylenedioxypyrovalerone, cocaine, and nomifensine significantly reduced uptake and increased vesicular DA release. In contrast, a low concentration of amphetamine reduced uptake but had no effect on DA release. Finally, the kappa opioid receptor agonist U50,488 significantly reduced vesicular DA release but had no effect on uptake. Together, these data demonstrate a novel analytical approach to distinguish the effects of manipulations on DA release or uptake that can be used to interpret FSCV data.

Has the National Cancer Screening Program reduced income inequalities in screening attendance in South Korea?

PubMed

Kim, Sujin; Kwon, Soonman; Subramanian, S V

2015-11-01

In 1999, the Korean government introduced the National Cancer Screening Program (NCSP) to increase the cancer-screening rate, particularly among the low-income population. This study investigates how the NCSP has decreased both relative and absolute income inequalities in the uptake of cancer screening in South Korea. A nationally representative cross-sectional repeated data from the Korea National Health and Nutrition Examination Survey 1998-2012, managed by the Ministry of Health and Welfare, was used to assess changes over time and the extent of discontinuity at the NCSP-recommended initiation age in the uptake of screening for breast, colorectal, and gastric cancers across income quartiles. Relative inequalities in the uptake of screening for all cancers decreased significantly over the policy period. Absolute inequalities did not change for most cancers, but marginally increased from 9 to 14% points in the uptake of screening for colorectal cancer among men. At the recommended initiation age, absolute inequalities did not change for breast and colorectal cancers but increased from 5 to 16% points for gastric cancer, for which relative inequality significantly decreased. The NCSP, which reduced out-of-pocket payment, may not decrease absolute gap although it leads to overall increases in the uptake of cancer screening and decreases in relative inequalities. Further investigations are needed to understand barriers that prevent the low-income population from attending cancer screening.

Synthesis and biological evaluation of (99m)Tc-DMP-NGA as a novel hepatic asialoglycoprotein receptor imaging agent.

PubMed

Yang, Wenjiang; Mou, Tiantian; Zhang, Xianzhong; Wang, Xuebin

2010-01-01

A novel bifunctional coupling agents-biomolecular compound DMP-NGA was prepared by coupling the SATP with galactosyl-neoglycoalbumin (NGA). The DMP-NGA was labeled with technetium-99m, and the radiochemical purity in excess of 98% after purified with HPLC. In vivo biodistribution showed that (99m)Tc-DMP-NGA had very high initial liver uptake with good retention. The liver accumulated 99.35+/-9.77%, 74.25+/-3.03%, 52.47+/-7.58% of the injected dose per gram at 5, 30 and 120min after injection, respectively. It had relative higher initial liver uptake and much lower blood uptake than that of (99m)Tc-GSA. The liver/blood ratio reached 83.4 at 30min post-injection, while the ratio of liver/kidney was 14.4. The uptakes in other organs in the abdomen were also slightly low. In addition, the hepatic uptake of (99m)Tc-DMP-NGA was blocked by preinjecting free GSA as blocking agent. The result indicates that (99m)Tc-DMP-NGA has specific binding to ASGP receptor. Images acquired with Kodak In-Vivo Imaging System FX Pro showed significant difference before and after inhibition. The promising biological properties of (99m)Tc-DMP-NGA afford potential applications in liver receptor imaging for assessment of hepatocyte function.

Predictors of Initial Uptake of Human Papillomavirus Vaccine Uptake Among Rural Appalachian Young Women

PubMed Central

Crosby, Richard A.; Vanderpool, Robin C.; Dignan, Mark; Bates, Wallace

2016-01-01

Women in Appalachian Kentucky experience a high burden of cervical cancer and have low rates of human papillomavirus (HPV) vaccination. The purpose of this study was to identify normative influences predicting initial HPV vaccine uptake among a sample of young women in southeastern Kentucky. Women (N = 495), ages 18 through 26 years, were recruited from clinics and community colleges. After completing a questionnaire, women received a free voucher for HPV vaccination. Whether women redeemed the voucher for Dose 1 served as the primary outcome variable. Hierarchical logistic regression was used to estimate the influence of healthcare providers, friends, mothers, and fathers on vaccine uptake. One-quarter of the total sample (25.9 %) received Dose 1. Uptake was higher in the clinic sample (45.1 %) than in the college sample (6.9 %). On multivariate analysis, women indicating that their healthcare provider suggested the vaccine, that their friends would “definitely” want them to be vaccinated, and that their fathers would “definitely” want them to receive the vaccine all were 1.6 times more likely to receive Dose 1. Interaction effects occurred between recruitment site (clinic vs. community college) and all three of the normative influences retaining multivariate significance, indicating that the associations only applied to the clinic sample. HPV vaccine interventions may benefit from highlighting paternal endorsement, healthcare provider recommendation, and peer support. PMID:23325057

Antibody uptake into neurons occurs primarily via clathrin-dependent Fcγ receptor endocytosis and is a prerequisite for acute tau protein clearance.

PubMed

Congdon, Erin E; Gu, Jiaping; Sait, Hameetha B R; Sigurdsson, Einar M

2013-12-06

Tau immunotherapy is effective in transgenic mice, but the mechanisms of Tau clearance are not well known. To this end, Tau antibody uptake was analyzed in brain slice cultures and primary neurons. Internalization was rapid (<1 h), saturable, and substantial compared with control mouse IgG. Furthermore, temperature reduction to 4 °C, an excess of unlabeled mouse IgG, or an excess of Tau antibodies reduced uptake in slices by 63, 41, and 62%, respectively (p = 0.002, 0.04, and 0.005). Uptake strongly correlated with total and insoluble Tau levels (r(2) = 0.77 and 0.87 and p = 0.002 and 0.0002), suggesting that Tau aggregates influence antibody internalization and/or retention within neurons. Inhibiting phagocytosis did not reduce uptake in slices or neuronal cultures, indicating limited microglial involvement. In contrast, clathrin-specific inhibitors reduced uptake in neurons (≤ 78%, p < 0.0001) and slices (≤ 35%, p = 0.03), demonstrating receptor-mediated endocytosis as the primary uptake pathway. Fluid phase endocytosis accounted for the remainder of antibody uptake in primary neurons, based on co-staining with internalized dextran. The receptor-mediated uptake is to a large extent via low affinity FcγII/III receptors and can be blocked in slices (43%, p = 0.04) and neurons (53%, p = 0.008) with an antibody against these receptors. Importantly, antibody internalization appears to be necessary for Tau reduction in primary neurons. Overall, these findings clarify that Tau antibody uptake is primarily receptor-mediated, that these antibodies are mainly found in neurons with Tau aggregates, and that their intracellular interaction leads to clearance of Tau pathology, all of which have major implications for therapeutic development of this approach.

Modification in digestive processing strategies to reduce toxic trace metal uptake in a marine bivalve

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

Decho, A.W.; Luoma, S.N.

1994-12-31

Bivalves possess two major digestion pathways for processing food particles: a rapid ``intestinal`` pathway where digestion is largely extracellular; and a slower ``glandular`` pathway where digestion is largely intracellular. The slower glandular pathway often results in more efficient absorption of carbon but also more efficient uptake of certain metals (e.g. Cr associated with bacteria). In the bivalve Potamocorbula amurensis, large portions (> 90%) of bacteria are selectively routed to the glandular pathway. This results in efficient C uptake but also efficient uptake of associated Cr. The authors further determined if prolonged exposure to Cr-contaminated bacteria would result in high Crmore » uptake by animals or whether mechanisms exist to reduce Cr exposure and uptake. Bivalves were exposed to natural food + added bacteria (with or without added Cr) for a 6-day period, then pulse-chase experiments were conducted to quantify digestive processing and % absorption efficiencies (%AE) of bacterial Cr. Bivalves compensate at low (2--5 ug/g sed) Cr by reducing overall food ingestion, while digestive processing of food remains statistically similar to controls. At high Cr (200--500 ug/g sed) there are marked decreases in % bacteria processed by glandular digestion. This results in lower overall %AE of Cr. The results suggest that bivalves under natural conditions might balance efficient carbon sequestration against avoiding uptake of potentially toxic metals associated the food.« less

In vitro kinetic investigations on the bioactivity and cytocompatibility of bioactive glasses prepared via melting and sol-gel techniques for bone regeneration applications.

PubMed

El-Sayed, Mayyada M H; Mostafa, Amany A; Gaafar, Alaa M; El Hotaby, Walid; Hamzawy, Esmat Ma; El-Okaily, Mohamed S; Gamal-Eldeen, Amira M

2017-02-24

This work investigates and compares the influence of the synthesis process on the in vitro bioactivity of two quaternary bioactive glasses prepared via melting and sol-gel (SG) techniques. The two glasses are named MG and SG, respectively. Powder samples were soaked in simulated body fluid for different time intervals to study the kinetics of Ca and P uptake onto their surface as well as Si release. The uptake kinetics followed the pseudo-second order model, and the kinetic parameters in addition to the initial rates were estimated. MG manifested higher Ca uptake capacity than SG which could be attributed to the presence of a residual organic layer capping the surface of SG, as was confirmed by Fourier transform infrared and nuclear magnetic resonance analyses. However, higher rate of Ca uptake was exhibited by SG probably due to its higher reactivity that resulted from its smaller nano-size and higher negative charge as was evident from transmission electron microscopy and dynamic light scattering measurements, respectively. Furthermore, MG showed slightly higher P uptake capacity and lower amount of Si release. Initial rates of Ca and P uptakes onto SG as well as Si release from SG exceeded those of MG. Human bone osteosarcoma cells (Saos-2) were co-cultured with both MG and SG glasses and the latter showed higher alkaline phosphatase activity and higher cell growth induction. The results showed the promising potential of using both bioactive glasses in bone regeneration. However, the choice of the appropriate bioactive glass depends on the targeted applications.

Summer peaks in uptake of human papillomavirus (HPV) and other adolescent vaccines in the United States

PubMed Central

Moss, Jennifer L.; Reiter, Paul L.; Rimer, Barbara K.; Ribisl, Kurt M.; Brewer, Noel T.

2015-01-01

Background Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer. Methods Data came from healthcare provider-verified vaccination records for 70,144 adolescents (ages 13–17) from the 2008–2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in uptake of HPV and other recommended adolescent vaccines (tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine). HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. Results Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all p<.001). Uptake was 5 times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all p<.001). Conclusion Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination. Impact The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them. PMID:26677211

Summer Peaks in Uptake of Human Papillomavirus and Other Adolescent Vaccines in the United States.

PubMed

Moss, Jennifer L; Reiter, Paul L; Rimer, Barbara K; Ribisl, Kurt M; Brewer, Noel T

2016-02-01

Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer. Data came from health care provider-verified vaccination records for 70,144 adolescents (ages 13-17 years) from the 2008 to 2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in the uptake of HPV and other recommended adolescent vaccines [tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine]. HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all P < 0.001). Uptake was five times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all P < 0.001). Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination. The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them. ©2015 American Association for Cancer Research.

The application of zero-valent iron nanoparticles for the remediation of a uranium-contaminated waste effluent.

PubMed

Dickinson, Michelle; Scott, Thomas B

2010-06-15

Zero-valent iron nanoparticles (INP) were investigated as a remediation strategy for a uranium-contaminated waste effluent from AWE, Aldermaston. Nanoparticles were introduced to the effluent, under both oxic and anoxic conditions, and allowed to react for a 28-d period during which the liquid and nanoparticle solids were periodically sampled. Analysis of the solution indicated that under both conditions U was removed to <1.5% of its initial concentration within 1h of introduction and remained at similar concentrations until approximately 48 h. A rapid release of Fe into solution was also recorded during this initial period; attributed to the limited partial dissolution of the INP. XPS analyses of the reacted nanoparticulate solids between 1 and 48 h showed an increased Fe(III):Fe(II) ratio, consistent with the detection of iron oxidation products (akaganeite and magnetite) by XRD and FIB. XPS analysis also recorded uranium on the recovered particulates indicating the chemical reduction of U(VI) to U(IV) within 1h. Following the initial retention period U-dissolution of U was recorded from 48 h, and attributed to reoxidation. The efficient uptake and retention of U on the INP for periods up to 48 h provide proof that INP may be effectively used for the remediation of complex U-contaminated effluents. Copyright 2010 Elsevier B.V. All rights reserved.

Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation.

PubMed

Zhang, Fan; Nance, Elizabeth; Alnasser, Yossef; Kannan, Rangaramanujam; Kannan, Sujatha

2016-03-22

Microglial cells have been implicated in neuroinflammation-mediated injury in the brain, including neurodevelopmental disorders such as cerebral palsy (CP) and autism. Pro-inflammatory activation of microglial cells results in the impairment of their neuroprotective functions, leading to an exaggerated, ongoing immune dysregulation that can persist long after the initial insult. We have previously shown that dendrimer-mediated delivery of an anti-inflammatory agent can attenuate inflammation in a rabbit model of maternal inflammation-induced CP and significantly improve the motor phenotype, due to the ability of the dendrimer to selectively localize in activated microglia. To elucidate the interactions between dendrimers and microglia, we created an organotypic whole-hemisphere brain slice culture model from newborn rabbits with and without exposure to inflammation in utero. We then used this model to analyze the dynamics of microglial migration and their interactions with dendrimers in the presence of neuroinflammation. Microglial cells in animals with CP had an amoeboid morphology and impaired cell migration, demonstrated by decreased migration distance and velocity when compared to cells in healthy, age-matched controls. However, this decreased migration was associated with a greater, more rapid dendrimer uptake compared to microglial cells from healthy controls. This study demonstrates that maternal intrauterine inflammation is associated with impaired microglial function and movement in the newborn brain. This microglial impairment may play a role in the development of ongoing brain injury and CP in the offspring. Increased uptake of dendrimers by the "impaired" microglia can be exploited to deliver drugs specifically to these cells and modulate their functions. Host tissue and target cell characteristics are important aspects to be considered in the design and evaluation of targeted dendrimer-based nanotherapeutics for improved and sustained efficacy. This ex vivo model also provides a rapid screening tool for evaluation of the effects of various therapies on microglial function.

Uptake mechanism for iodine species to black carbon.

PubMed

Choung, Sungwook; Um, Wooyong; Kim, Minkyung; Kim, Min-Gyu

2013-09-17

Natural organic matter (NOM) plays an important role in determining the fate and transport of iodine species such as iodide (I(-)) and iodate (IO3(-)) in groundwater system. Although NOM exists as diverse forms in environments, prior iodine studies have mainly focused on uptake processes of iodide and iodate to humic materials. This study was conducted to determine the iodide and iodate uptake potential for a particulate NOM (i.e., black carbon [BC]). A laboratory-produced BC and commercial humic acid were used for batch experiments to compare their iodine uptake properties. The BC exhibited >100 times greater uptake capability for iodide than iodate at low pH of ~3, while iodide uptake was negligible for the humic acid. The uptake properties of both solids strongly depend on the initial iodine aqueous concentrations. After uptake reaction of iodide to the BC, X-ray absorption fine structure spectroscopy results indicated that the iodide was converted to electrophilic species, and iodine was covalently bound to carbon atom in polycyclic aromatic hydrocarbons present in the BC. The computed distribution coefficients (i.e., Kd values) suggest that the BC materials retard significantly the transport of iodide at low pH in environmental systems containing even a small amount of BC.

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

PubMed Central

Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

2016-01-01

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

Studies on uptake of trivalent and hexavalent chromium by maize (Zea mays).

PubMed

Mishra, S; Singh, V; Srivastava, S; Srivastava, R; Srivastava, M M; Dass, S; Satsangi, G P; Prakash, S

1995-05-01

Pot culture experiments were carried out to study the uptake and translocation of chromium from irrigation water when supplied in its trivalent and hexavalent states to maize plants grown in soil and sand culture. The uptake of chromium was observed to increase with increase in the concentration for both oxidation states of chromium. For the root, the observed order of uptake was CrIII sand > CrVI sand > CrIII soil > CrVI soil, whereas in the lower shoot, upper shoot and fruit the order was CrVI sand > CrVI soil > CrIII sand > CrIII soil. Significantly high uptake of chromium by roots in the sand culture (CrIII treatment) is attributed to the effect of root exudates and degradation products on the mobilization of CrIII. In aerial parts of the plants a higher uptake was observed when the initial supply was CrVI. The trends observed are explained on the basis of the redox behaviour of chromium.

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells.

PubMed

Kraehling, Jan R; Chidlow, John H; Rajagopal, Chitra; Sugiyama, Michael G; Fowler, Joseph W; Lee, Monica Y; Zhang, Xinbo; Ramírez, Cristina M; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L; Fernández-Hernando, Carlos; Sessa, William C

2016-11-21

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL.

Attitudes and beliefs to the uptake and maintenance of physical activity among community-dwelling South Asians aged 60-70 years: a qualitative study.

PubMed

Horne, M; Skelton, D A; Speed, S; Todd, C

2012-05-01

To identify the attitudes and beliefs associated with the uptake and adherence of physical activity among community-dwelling South Asians aged 60-70 years. A qualitative research study using an ethnographic approach. Focus groups and in-depth interviews were conducted to explore motivational factors associated with initiating and maintaining physical activity. Data analysis followed the framework approach. Health, maintaining independence and social support were important in terms of initiating physical activity. Social support, psychosocial elements of activity, health and integrating physical activity within everyday activities were important for adherence to physical activity. The need for gendered physical activity sessions was important to initiating exercise among Muslim South Asians aged 60-70 years. Promoting active lifestyles and building physical activity in and around day-to-day activities are important strategies in increasing activity levels. However, the needs for culturally appropriate facilities, peer mentors who could assist those with language barriers, specific tailored advice, advice on integrating physical activity in everyday life and general social support could promote uptake and subsequent adherence among this population group. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Urban Stream Burial Increases Watershed-Scale Nitrate Export.

PubMed

Beaulieu, Jake J; Golden, Heather E; Knightes, Christopher D; Mayer, Paul M; Kaushal, Sujay S; Pennino, Michael J; Arango, Clay P; Balz, David A; Elonen, Colleen M; Fritz, Ken M; Hill, Brian H

2015-01-01

Nitrogen (N) uptake in streams is an important ecosystem service that reduces nutrient loading to downstream ecosystems. Here we synthesize studies that investigated the effects of urban stream burial on N-uptake in two metropolitan areas and use simulation modeling to scale our measurements to the broader watershed scale. We report that nitrate travels on average 18 times farther downstream in buried than in open streams before being removed from the water column, indicating that burial substantially reduces N uptake in streams. Simulation modeling suggests that as burial expands throughout a river network, N uptake rates increase in the remaining open reaches which somewhat offsets reduced N uptake in buried reaches. This is particularly true at low levels of stream burial. At higher levels of stream burial, however, open reaches become rare and cumulative N uptake across all open reaches in the watershed rapidly declines. As a result, watershed-scale N export increases slowly at low levels of stream burial, after which increases in export become more pronounced. Stream burial in the lower, more urbanized portions of the watershed had a greater effect on N export than an equivalent amount of stream burial in the upper watershed. We suggest that stream daylighting (i.e., uncovering buried streams) can increase watershed-scale N retention.

Urban Stream Burial Increases Watershed-Scale Nitrate Export

PubMed Central

Beaulieu, Jake J.; Golden, Heather E.; Knightes, Christopher D.; Mayer, Paul M.; Kaushal, Sujay S.; Pennino, Michael J.; Arango, Clay P.; Balz, David A.; Elonen, Colleen M.; Fritz, Ken M.; Hill, Brian H.

2015-01-01

Nitrogen (N) uptake in streams is an important ecosystem service that reduces nutrient loading to downstream ecosystems. Here we synthesize studies that investigated the effects of urban stream burial on N-uptake in two metropolitan areas and use simulation modeling to scale our measurements to the broader watershed scale. We report that nitrate travels on average 18 times farther downstream in buried than in open streams before being removed from the water column, indicating that burial substantially reduces N uptake in streams. Simulation modeling suggests that as burial expands throughout a river network, N uptake rates increase in the remaining open reaches which somewhat offsets reduced N uptake in buried reaches. This is particularly true at low levels of stream burial. At higher levels of stream burial, however, open reaches become rare and cumulative N uptake across all open reaches in the watershed rapidly declines. As a result, watershed-scale N export increases slowly at low levels of stream burial, after which increases in export become more pronounced. Stream burial in the lower, more urbanized portions of the watershed had a greater effect on N export than an equivalent amount of stream burial in the upper watershed. We suggest that stream daylighting (i.e., uncovering buried streams) can increase watershed-scale N retention. PMID:26186731

Crassulacean acid metabolism, CO2-recycling, and tissue desiccation in the Mexican epiphyte Tillandsia schiedeana Steud (Bromeliaceae).

PubMed

Martin, C E; Adams, W W

1987-01-01

After 23 days without water in a greenhouse, rates of nocturnal CO2 uptake in Tillandsia schiedeana decreased substantially and maximum rates occurred later in the dark period eventually coinciding with the onset of illumination. Nocturnal CO2 uptake accounted for less than half the total nighttime increase in acidity measured in well-watered plants. With increased tissue desiccation, only 11-12% of measured acid accumulation was attributable to atmospheric CO2 uptake. Plants desiccated for 30 days regained initial levels of nocturnal acid accumulation and CO2 uptake after rehydration for 10h. These results stress the importance of CO2 recycling via CAM in this epiphytic bromeliad, especially during droughts.

Drought Rapidly Diminishes the Large Net CO2 Uptake in 2011 Over Semi-Arid Australia

NASA Technical Reports Server (NTRS)

Ma, Xuanlong; Huete, Alfredo; Cleverly, James; Eamus, Derek; Chevallier, Frederic; Joiner, Joanna; Poulter, Benjamin; Zhang, Yongguang; Guanter, Luis; Meyer, Wayne;

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

Salminen, S.O.; Streeter, J.G.

Bradyrhizobium japonicum bacteroids were isolated anaerobically and were supplied with /sup 14/C-labeled trehalose, sucrose, UDP-glucose, glucose, or fructose under low O/sub 2/ (2% in the gas phase). Uptake and conversion of /sup 14/C to CO/sub 2/ were measured at intervals up to 90 minutes. Of the five compounds studied, UDP-glucose was most rapidly absorbed but it was very slowly metabolized. Trehalose was the sugar most rapidly converted to CO/sub 2/, and fructose was respired at a rate of at least double that of glucose. Sucrose and glucose were converted to CO/sub 2/ at a very low but measurable rate (<0.1more » nanomoles per milligram protein per hour). Carbon Number 1 of glucose appeared in CO/sub 2/ at a rate 30 times greater than the conversion of carbon Number 6 to CO/sub 2/, indicating high activity of the pentose phosphate pathway. Enzymes of the Entner-Doudoroff pathway were not detected in bacteroids, but very low activities of sucrose synthase and phosphofructokinase were demonstrated. Although metabolism of sugars by B. japonicum bacteroids was clearly demonstrated, the rate of sugar uptake was only 1/30 to 1/50 the rate of succinate uptake. The overall results support the view that, although bacteroids metabolize sugars, the rates are very low and are inadequate to support nitrogenase.« less

Drought rapidly diminishes the large net CO2 uptake in 2011 over semi-arid Australia

NASA Astrophysics Data System (ADS)

Ma, Xuanlong; Huete, Alfredo; Cleverly, James; Eamus, Derek; Chevallier, Frédéric; Joiner, Joanna; Poulter, Benjamin; Zhang, Yongguang; Guanter, Luis; Meyer, Wayne; Xie, Zunyi; Ponce-Campos, Guillermo

2016-11-01

Each year, terrestrial ecosystems absorb more than a quarter of the anthropogenic carbon emissions, termed as land carbon sink. An exceptionally large land carbon sink anomaly was recorded in 2011, of which more than half was attributed to Australia. However, the persistence and spatially attribution of this carbon sink remain largely unknown. Here we conducted an observation-based study to characterize the Australian land carbon sink through the novel coupling of satellite retrievals of atmospheric CO2 and photosynthesis and in-situ flux tower measures. We show the 2010-11 carbon sink was primarily ascribed to savannas and grasslands. When all biomes were normalized by rainfall, shrublands however, were most efficient in absorbing carbon. We found the 2010-11 net CO2 uptake was highly transient with rapid dissipation through drought. The size of the 2010-11 carbon sink over Australia (0.97 Pg) was reduced to 0.48 Pg in 2011-12, and was nearly eliminated in 2012-13 (0.08 Pg). We further report evidence of an earlier 2000-01 large net CO2 uptake, demonstrating a repetitive nature of this land carbon sink. Given a significant increasing trend in extreme wet year precipitation over Australia, we suggest that carbon sink episodes will exert greater future impacts on global carbon cycle.

Drought rapidly diminishes the large net CO2 uptake in 2011 over semi-arid Australia.

PubMed

Ma, Xuanlong; Huete, Alfredo; Cleverly, James; Eamus, Derek; Chevallier, Frédéric; Joiner, Joanna; Poulter, Benjamin; Zhang, Yongguang; Guanter, Luis; Meyer, Wayne; Xie, Zunyi; Ponce-Campos, Guillermo

2016-11-25

Each year, terrestrial ecosystems absorb more than a quarter of the anthropogenic carbon emissions, termed as land carbon sink. An exceptionally large land carbon sink anomaly was recorded in 2011, of which more than half was attributed to Australia. However, the persistence and spatially attribution of this carbon sink remain largely unknown. Here we conducted an observation-based study to characterize the Australian land carbon sink through the novel coupling of satellite retrievals of atmospheric CO 2 and photosynthesis and in-situ flux tower measures. We show the 2010-11 carbon sink was primarily ascribed to savannas and grasslands. When all biomes were normalized by rainfall, shrublands however, were most efficient in absorbing carbon. We found the 2010-11 net CO 2 uptake was highly transient with rapid dissipation through drought. The size of the 2010-11 carbon sink over Australia (0.97 Pg) was reduced to 0.48 Pg in 2011-12, and was nearly eliminated in 2012-13 (0.08 Pg). We further report evidence of an earlier 2000-01 large net CO 2 uptake, demonstrating a repetitive nature of this land carbon sink. Given a significant increasing trend in extreme wet year precipitation over Australia, we suggest that carbon sink episodes will exert greater future impacts on global carbon cycle.

High in Vivo Stability of 64Cu-Labeled Cross-Bridged Chelators Is a Crucial Factor in Improved Tumor Imaging of RGD Peptide Conjugates.

PubMed

Sarkar, Swarbhanu; Bhatt, Nikunj; Ha, Yeong Su; Huynh, Phuong Tu; Soni, Nisarg; Lee, Woonghee; Lee, Yong Jin; Kim, Jung Young; Pandya, Darpan N; An, Gwang Il; Lee, Kyo Chul; Chang, Yongmin; Yoo, Jeongsoo

2018-01-11

Although the importance of bifunctional chelators (BFCs) is well recognized, the chemophysical parameters of chelators that govern the biological behavior of the corresponding bioconjugates have not been clearly elucidated. Here, five BFCs closely related in structure were conjugated with a cyclic RGD peptide and radiolabeled with Cu-64 ions. Various biophysical and chemical properties of the Cu(II) complexes were analyzed with the aim of identifying correlations between individual factors and the biological behavior of the conjugates. Tumor uptake and body clearance of the 64 Cu-labeled bioconjugates were directly compared by animal PET imaging in animal models, which was further supported by biodistribution studies. Conjugates containing propylene cross-bridged chelators showed higher tumor uptake, while a closely related ethylene cross-bridged analogue exhibited rapid body clearance. High in vivo stability of the copper-chelator complex was strongly correlated with high tumor uptake, while the overall lipophilicity of the bioconjugate affected both tumor uptake and body clearance.

Relation between the location of elements in the periodic table and various organ-uptake rates.

PubMed

Ando, A; Ando, I; Hiraki, T; Hisada, K

1989-01-01

Fifty four elements and 65 radioactive compounds were examined to determine the organ uptake rates for rats 3, 24 and 48 h after i.v. injection of these compounds. They were prepared as carrier free nuclides, or containing a small amount of stable nuclide. Generally speaking, behaviors of K, Rb, Cs and Tl in all the organs were very similar to one another, but they differed from that of Na. Bivalent hard acids were avidly taken up into bone; therefore, uptake rates in soft tissues were very small. Hard acids of tri-, quadri- and pentavalence which were taken up into the soft tissue organs decreased more slowly from these organs than other ions. Soft acids such as Hg2+ were bound very firmly to the component in the kidney. Anions (with few exceptions), GeCl4 and SbCl3 were rapidly excreted in urine, so that the uptake rates in organs were low.

Development of [18F]DASA-23 for Imaging Tumor Glycolysis Through Noninvasive Measurement of Pyruvate Kinase M2.

PubMed

Beinat, Corinne; Alam, Israt S; James, Michelle L; Srinivasan, Ananth; Gambhir, Sanjiv Sam

2017-10-01

A hallmark of cancer is metabolic reprogramming, which is exploited by cancer cells to ensure rapid growth and survival. Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key step in tumor metabolism and growth. Recently, we reported the radiosynthesis of the first positron emission tomography tracer for visualizing PKM2 in vivo-i.e., [ 11 C]DASA-23. Due to the highly promising imaging results obtained with [ 11 C]DASA-23 in rodent model glioblastoma, we set out to generate an F-18-labeled version of this tracer, with the end goal of clinical translation in mind. Herein, we report the radiosynthesis of 1-((2-fluoro-6-[ 18 F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([ 18 F]DASA-23) and our initial investigation of its binding properties in cancer cells. We synthesized [ 18 F]DASA-23 via fluorination of 1-((2-fluoro-6-nitrophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine (10) with K[ 18 F]F/K2.2.2 in N,N-dimethylformamide at 110 °C for 20 min. Subsequently, we evaluated uptake of [ 18 F]DASA-23 in HeLa cervical adenocarcinoma cells and in vitro stability in human and mouse serum. We successfully prepared [ 18 F]DASA-23 in 2.61 ± 1.54 % radiochemical yield (n = 10, non-decay corrected at end of synthesis) with a specific activity of 2.59 ± 0.44 Ci/μmol. Preliminary cell uptake experiments revealed high uptake in HeLa cells, which was effectively blocked by pretreating cells with the structurally distinct PKM2 activator, TEPP-46. [ 18 F]DASA-23 remained intact in human and mouse serum up to 120 min. Herein, we have identified a F-18-labeled PKM2 specific radiotracer which shows potential for in vivo imaging. The promising cell uptake results reported herein warrant the further evaluation of [ 18 F]DASA-23 for its ability to detect and monitor cancer noninvasively.

Rapid sodium signaling couples glutamate uptake to breakdown of ATP in perivascular astrocyte endfeet.

PubMed

Langer, Julia; Gerkau, Niklas J; Derouiche, Amin; Kleinhans, Christian; Moshrefi-Ravasdjani, Behrouz; Fredrich, Michaela; Kafitz, Karl W; Seifert, Gerald; Steinhäuser, Christian; Rose, Christine R

2017-02-01

Perivascular endfeet of astrocytes are highly polarized compartments that ensheath blood vessels and contribute to the blood-brain barrier. They experience calcium transients with neuronal activity, a phenomenon involved in neurovascular coupling. Endfeet also mediate the uptake of glucose from the blood, a process stimulated in active brain regions. Here, we demonstrate in mouse hippocampal tissue slices that endfeet undergo sodium signaling upon stimulation of glutamatergic synaptic activity. Glutamate-induced endfeet sodium transients were diminished by TFB-TBOA, suggesting that they were generated by sodium-dependent glutamate uptake. With local agonist application, they could be restricted to endfeet and immunohistochemical analysis revealed prominent expression of glutamate transporters GLAST and GLT-1 localized towards the neuropil vs. the vascular side of endfeet. Endfeet sodium signals spread at an apparent maximum velocity of ∼120 µm/s and directly propagated from stimulated into neighboring endfeet; this spread was omitted in Cx30/Cx43 double-deficient mice. Sodium transients resulted in elevation of intracellular magnesium, indicating a decrease in intracellular ATP. In summary, our results establish that excitatory synaptic activity and stimulation of glutamate uptake in astrocytes trigger transient sodium increases in perivascular endfeet which rapidly spread through gap junctions into neighboring endfeet and cause a reduction of intracellular ATP. The newly discovered endfeet sodium signaling thereby represents a fast, long-lived and inter-cellularly acting indicator of synaptic activity at the blood-brain barrier, which likely constitutes an important component of neuro-metabolic coupling in the brain. GLIA 2017;65:293-308. © 2016 Wiley Periodicals, Inc.

Decadal evolution of the surface energy budget during the fast warming and global warming hiatus periods in the ERA-interim

NASA Astrophysics Data System (ADS)

Hu, Xiaoming; Sejas, Sergio A.; Cai, Ming; Taylor, Patrick C.; Deng, Yi; Yang, Song

2018-05-01

The global-mean surface temperature has experienced a rapid warming from the 1980s to early-2000s but a muted warming since, referred to as the global warming hiatus in the literature. Decadal changes in deep ocean heat uptake are thought to primarily account for the rapid warming and subsequent slowdown. Here, we examine the role of ocean heat uptake in establishing the fast warming and warming hiatus periods in the ERA-Interim through a decomposition of the global-mean surface energy budget. We find the increase of carbon dioxide alone yields a nearly steady increase of the downward longwave radiation at the surface from the 1980s to the present, but neither accounts for the fast warming nor warming hiatus periods. During the global warming hiatus period, the transfer of latent heat energy from the ocean to atmosphere increases and the total downward radiative energy flux to the surface decreases due to a reduction of solar absorption caused primarily by an increase of clouds. The reduction of radiative energy into the ocean and the surface latent heat flux increase cause the ocean heat uptake to decrease and thus contribute to the slowdown of the global-mean surface warming. Our analysis also finds that in addition to a reduction of deep ocean heat uptake, the fast warming period is also driven by enhanced solar absorption due predominantly to a decrease of clouds and by enhanced longwave absorption mainly attributed to the air temperature feedback.

177 Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice

DOE PAGES

Choy, Cindy J.; Ling, Xiaoxi; Geruntho, Jonathan J.; ...

2017-04-27

Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a 177Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401). The radiolabeling of CTT1401 and CTT1403 was achieved using click chemistrymore » to connect 177Lu-DOTA-N3 to the dibenzocyclooctyne (DBCO)-bearing CTT1298 inhibitor cores. A direct comparison in vitro and in vivo performance was made for CTT1401 and CTT1403; the specificity and efficacy by means of cellular uptake and internalization, biodistribution, and therapeutic efficacy were determined for both compounds. And while both compounds displayed excellent uptake and rapid internalization in PSMA+ PC3-PIP cells, the albumin binding moiety in CTT1403 conferred clear advantages to the PSMA-inhibitor scaffold including increased circulating half-life and prostate tumor uptake that continued to increase up to 168 h post-injection. This then increased tumor uptake translated into superior therapeutic efficacy of CTT1403 in PSMA+ PC3-PIP human xenograft tumors.« less

177 Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice

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

Choy, Cindy J.; Ling, Xiaoxi; Geruntho, Jonathan J.

Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a 177Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401). The radiolabeling of CTT1401 and CTT1403 was achieved using click chemistrymore » to connect 177Lu-DOTA-N3 to the dibenzocyclooctyne (DBCO)-bearing CTT1298 inhibitor cores. A direct comparison in vitro and in vivo performance was made for CTT1401 and CTT1403; the specificity and efficacy by means of cellular uptake and internalization, biodistribution, and therapeutic efficacy were determined for both compounds. And while both compounds displayed excellent uptake and rapid internalization in PSMA+ PC3-PIP cells, the albumin binding moiety in CTT1403 conferred clear advantages to the PSMA-inhibitor scaffold including increased circulating half-life and prostate tumor uptake that continued to increase up to 168 h post-injection. This then increased tumor uptake translated into superior therapeutic efficacy of CTT1403 in PSMA+ PC3-PIP human xenograft tumors.« less

Visualization of self-delivering hydrophobically modified siRNA cellular internalization

PubMed Central

Ly, Socheata; Navaroli, Deanna M.; Didiot, Marie-Cécile; Cardia, James; Pandarinathan, Lakshmipathi; Alterman, Julia F.; Fogarty, Kevin; Standley, Clive; Lifshitz, Lawrence M.; Bellve, Karl D.; Prot, Matthieu; Echeverria, Dimas; Corvera, Silvia; Khvorova, Anastasia

2017-01-01

siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs®) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation of vesicular structures and internalization. Furthermore, sd-rxRNAs are internalized by a specific class of early endosomes and show preferential association with epidermal growth factor (EGF) but not transferrin (Tf) trafficking pathways as shown by live cell TIRF and structured illumination microscopy (SIM). In fixed cells, we observe ∼25% of sd-rxRNA co-localizing with EGF and <5% with Tf, which is indicative of selective endosomal sorting. Likewise, preferential sd-rxRNA co-localization was demonstrated with EEA1 but not RBSN-containing endosomes, consistent with preferential EGF-like trafficking through EEA1-containing endosomes. sd-rxRNA cellular uptake is a two-step process, with rapid membrane association followed by internalization through a selective, saturable subset of the endocytic process. However, the mechanistic role of EEA1 is not yet known. This method of visualization can be used to better understand the kinetics and mechanisms of hydrophobic siRNA cellular uptake and will assist in further optimization of these types of compounds for therapeutic intervention. PMID:27899655

Dramatic effects of external alkalinity on neuronal calcium recovery following a short-duration glutamate challenge: the role of the plasma membrane Ca2+/H+ pump.

PubMed

Khodorov, B; Pinelis, V; Vergun, O; Storozhevykh, T; Fajuk, D; Vinskaya, N; Arsenjeva, E; Khaspekov, L; Lyzin, A; Isaev, N

1995-09-11

Alkalinization of the external medium has been shown to suppress Ca2+ extrusion from neurons due to inhibition of the plasmalemmal Ca2+/H+ pump. In our experiments on fura-2-loaded rat cerebellar granule cells and mouse hippocampal neurons, an increase in pHo from 7.4 to 8.5 following a 1-min glutamate or NMDA challenge caused a dramatic delay in [Ca2+]i recovery which in some cases was accompanied by an additional increase in [Ca2+]i. Normalization of pHo, or removal of Ca2+ from the alkaline solution allowed [Ca2+]i to decrease rapidly again. External alkalinity did not affect the initial rapid decline in [Ca2+]i following a 25 mMK+ pulse. In cerebellar granule cells, the alkaline pHo considerably increased the 45Ca2+ uptake both at rest and following a 2-min GLU pulse. A comparison of these effects of alkaline pHo with those produced by removal of the external Na+ led us to conclude that the Ca2+/H+ pump plays a dominant role in the mechanism of the fast Ca2+ extrusion from glutamate- or NMDA-treated neurons.

Nerves and Tissue Repair.

DTIC Science & Technology

1994-07-01

axolotl limbs are transected the concentration of transferrin in the distal limb tissue declines rapidly and limb regeneration stops. These results...transferrin binding and expression of the transferrin gene in cells of axolotl peripheral nerve indicate that both uptake and synthesis of this factor occur

Introduction of a new Rotavirus vaccine: Initial results of uptake and impact on laboratory confirmed cases in Anglia and Essex, United Kingdom, July 2015.

PubMed

Inns, Thomas; Trindall, Amy; Dunling-Hall, Sara; Shankar, Ananda Giri

2016-04-02

Rotavirus gastroenteritis accounts for an estimated 130,000 GP consultations and 13,000 hospitalisations for children under 5 y old each year in England and Wales. In July 2013, an oral live attenuated rotavirus vaccine (Rotarix®) was introduced into the UK infant immunisation program as a 2 dose schedule at 2 and 3 months of age. We collected vaccination uptake from October 2013 to March 2015 and laboratory confirmed cases data on children under the age of 5 y from 1 January 2004 to 31 May 2015. The vaccine uptake rates and laboratory confirmed cases were compared to provide evidence of the impact of this vaccination program. Vaccine uptake rates were available from sentinel data with between 91-98% of GP practices in Anglia and Essex providing data every month. These data showed from February 2014 to March 2015 between 90-92% of infants received the recommended 2 doses of Rotarix® each month. The numbers of rotavirus cases reported by laboratories decreased on average by 82% in the post vaccination seasons. The mean number of cases reported in weeks 1-22 for 2004-2013 in Anglia and Essex was 1,318. For the same period in 2014, 256 cases were reported and initial data for 2015 report 226 cases. In the first 5 months 2014 the greatest reduction in cases (89%) was seen in those under 1 yr (who would have been directly affected by vaccination) with case numbers falling to 59 from a mean 537 cases in the equivalent period for 2004-2013. Initially data suggests a 92% reduction in 2015 compared to the same pre-vaccination periods. For those aged 1 to <5 y who would not have been vaccinated, a reduction of 75% was also evident in 2014 and 77% in 2015, suggesting indirect protection in this group. In conclusion, initial results following the introduction of the Rotavirus vaccine clearly indicates a very good uptake of the vaccine and a significant reduction in the numbers of laboratory confirmed cases.

Introduction of a new Rotavirus vaccine: Initial results of uptake and impact on laboratory confirmed cases in Anglia and Essex, United Kingdom, July 2015

PubMed Central

Inns, Thomas; Trindall, Amy; Dunling-Hall, Sara; Shankar, Ananda Giri

2016-01-01

abstract Rotavirus gastroenteritis accounts for an estimated 130,000 GP consultations and 13,000 hospitalisations for children under 5 y old each year in England and Wales. In July 2013, an oral live attenuated rotavirus vaccine (Rotarix®) was introduced into the UK infant immunisation program as a 2 dose schedule at 2 and 3 months of age. We collected vaccination uptake from October 2013 to March 2015 and laboratory confirmed cases data on children under the age of 5 y from 1 January 2004 to 31 May 2015. The vaccine uptake rates and laboratory confirmed cases were compared to provide evidence of the impact of this vaccination program. Vaccine uptake rates were available from sentinel data with between 91–98% of GP practices in Anglia and Essex providing data every month. These data showed from February 2014 to March 2015 between 90–92% of infants received the recommended 2 doses of Rotarix® each month. The numbers of rotavirus cases reported by laboratories decreased on average by 82% in the post vaccination seasons. The mean number of cases reported in weeks 1–22 for 2004–2013 in Anglia and Essex was 1,318. For the same period in 2014, 256 cases were reported and initial data for 2015 report 226 cases. In the first 5 months 2014 the greatest reduction in cases (89%) was seen in those under 1 yr (who would have been directly affected by vaccination) with case numbers falling to 59 from a mean 537 cases in the equivalent period for 2004–2013. Initially data suggests a 92% reduction in 2015 compared to the same pre-vaccination periods. For those aged 1 to <5 y who would not have been vaccinated, a reduction of 75% was also evident in 2014 and 77% in 2015, suggesting indirect protection in this group. In conclusion, initial results following the introduction of the Rotavirus vaccine clearly indicates a very good uptake of the vaccine and a significant reduction in the numbers of laboratory confirmed cases. PMID:26618660

Processes of nickel and cobalt uptake by a manganese oxide forming sediment in Pinal Creek, Globe mining district, Arizona

USGS Publications Warehouse

Kay, J.T.; Conklin, M.H.; Fuller, C.C.; O'Day, P. A.

2001-01-01

A series of column experiments was conducted using manganese oxide coated sediments collected from the hyporheic zone in Pinal Creek (AZ), a metal-contaminated stream, to study the uptake and retention of Mn, Ni, and Co. Experimental variables included the absence (abiotic) and presence (biotic) of active Mn-oxidizing bacteria, the absence and presence of dissolved Mn, and sediment manganese oxide content. Uptake of Mn under biotic conditions was between 8 and 39% higher than under abiotic conditions. Continuous uptake of Mn due to biotic oxidation was evident from extraction of column sediments. Manganese uptake is hypothesized to initially occur as adsorption, which led to subsequent surface and/or microbial oxidation. Complete breakthrough of Ni within 100 pore volumes indicated no process of continuous uptake and was modeled as an equilibrium adsorption process. Nickel uptake in the presence of dissolved Mn was 67-100% reversible. Sediment extractions suggest that Ni uptake occurred through weak and strong adsorption. Continuous uptake of cobalt increased with sediment manganese oxide content, and Co uptake was up to 75% greater under biotic than abiotic conditions. Cobalt uptake was controlled by both existing and newly formed manganese oxides. Only a small amount of Co uptake was reversible (10-25%). XANES spectral analysis indicated that most Co(II) was oxidized to Co(III) and probably incorporated structurally into manganese oxides. Although manganese oxides were the primary phase controlling uptake and retention of Mn, Ni, and Co, the mechanisms varied among the metals.

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment

PubMed Central

Li, Min; Wang, Li; Liu, Jiang-Hong; Zhan, Shu-Qin

2018-01-01

Objective: Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. Data Sources: Using the combined keywords: “RBD”, “neurodegenerative disease”, “Parkinson disease”, and “magnetic resonance imaging”, the PubMed/MEDLINE literature search was conducted up to January 1, 2018. Study Selection: A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. Results: Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. Conclusions: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases. PMID:29664058

Injury-induced rapid activation of MAPK signaling in dechorionated eggs and larvae of the silkworm Bombyx mori.

PubMed

Gu, Shi-Hong; Chen, Chien-Hung

2017-04-01

Previous study showed that diapause in Bombyx mori eggs can be terminated by dechorionation and that activation in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) in dechorionated cultured eggs is involved in diapause termination. In the present study, the possible mechanism underlying activation of ERK upon dechorionation was further investigated. Results showed that mechanical injury of diapause eggs without medium incubation also resulted in rapid increase in the phospho-ERK levels and that injury increased the phospho-ERK levels at different stages of both diapause eggs and eggs in which diapause initiation was prevented by HCl. Effects of anaerobiosis on dechorionation-stimulated phospho-ERK levels showed that the mechanical injury itself but not the dramatic increase in oxygen uptake upon injury is involved in a rapid activation of ERK. Chemical anaerobiosis on dechorionation-stimulated phospho-ERK levels and the in vivo effect of anaerobiosis showed that the supply of oxygen also plays a role in ERK signaling. In addition, injury induced the phosphorylation of c-jun N-terminal kinases (JNKs) and p38 kinase, components of two parallel MAPK pathways. A kinase assay showed a dramatic increase in JNK kinase activity in egg lysates upon injury. When newly hatched first instar larvae were injured, an increase in the phospho-ERK levels similar to that in dechorionated eggs was observed. From the results, we hypothesize that the injury-induced rapid activation of MAPK signaling, which serves as a natural signal for embryonic development, is related to diapause termination in dechorionated eggs. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Hiatal hernia uptake of iodine-131 mimicking mediastinal metastasis of papillary thyroid carcinoma.

PubMed

Haghighatafshar, Mahdi; Khajehrahimi, Farnaz

2015-01-01

There are a few case reports of hiatal hernia demonstrating thoracic uptake on I-131 scintigraphy. In this case, high thyroglobulin levels in combination with misinterpretation of I-131 uptake in the mediastinum, leaded to mismanagement of the patient. Here we present a case of focal I-131 uptake within a hiatal hernia initially mimicking an isolated mediastinal metastasis. There are many potential causes of false-positive I-131 scan result. In this case, adjunctive chest computed tomography and gastroesophageal barium study helped to elucidate the true nature of this I-131 uptake. False-positive findings may be caused by a wide variety of nonthyroidal carcinomas, which can concentrate radioiodine or from skin contamination. Several organs, such as the gastric, salivary glands, renal cyst, pericardial effusion, and ovarian can accumulate I-131. It should be borne in mind as a potential source of false-positive whole-body I-131 imaging.

HPV vaccination uptake among Cambodian mothers.

PubMed

Taylor, Victoria M; Burke, Nancy; Do, Hoai; Liu, Qi; Yasui, Yutaka; Bastani, Roshan

2012-03-01

Women of Southeast Asian descent have higher cervical cancer incidence rates than any other group. Widespread use of HPV vaccination could prevent up to 70% of cervical cancers. There is little published information addressing HPV vaccination uptake among Asian Americans. We conducted a survey of Cambodian women with daughters who were age-eligible for HPV vaccination. Survey items addressed HPV vaccination barriers, facilitators, and uptake. Only 26% of the survey participants reported any of their age-eligible daughters had received vaccination, and only 40% reported a previous physician recommendation for vaccination. Higher levels of vaccine uptake were strongly associated with having received a doctor's recommendation for vaccination (p < 0.001) and having asked a doctor for vaccination (p = 0.002). HPV vaccine uptake was relatively low in our Cambodian study group. Educational initiatives should encourage health care providers who serve Cambodian families to recommend HPV vaccination and empower Cambodian mothers to ask their daughters' doctors for vaccination.

Comparison of in vitro fluoride uptake from whitening toothpastes and a conventional toothpaste in demineralised enamel.

PubMed

Altenburger, Markus J; Bernhart, Jasmin; Schicha, Thurid D; Wrbas, Karl-Thomas; Hellwig, Elmar

2010-01-01

Studies on the compatibility of abrasives and fluoride compounds deal exclusively with fluoride uptake and remineralization after storing the enamel specimens in a toothpaste-saliva mixture. The influence of brushing on the fluoride uptake when highly abrasive toothpastes are used has hardly been investigated so far. The aim of the present study was to investigate fluoride uptake in initially demineralised dental enamel after storage in, or brushing with, whitening toothpaste slurries, compared to a conventional toothpaste. For this purpose two widely available whitening toothpastes with ionically bound fluoride (sodium fluoride NaF), two with covalently-bound fluoride toothpastes (sodium monofluorophosphate, NaMFP) and a conventional amine fluoride toothpaste (AmF) were compared. The fluoride uptake after use of the AmF toothpaste was shown to be statistically significantly higher than that after application of the NaF toothpastes, which in turn was statistically significantly higher than the uptake resulting from NaMFP application. The fluoride uptake was slightly higher when the enamel samples were brushed with NaF toothpaste, rather than just stored in the respective toothpaste slurry. Brushing with highly abrasive toothpastes did not negatively influence fluoride uptake in demineralised dental enamel. The ionic form of the fluoride in toothpastes appears to be critical for increased fluoride uptake. The acidic components of the AmF toothpaste improved fluoride uptake compared to alkaline NaF toothpastes.

Struma Ovarii With Hyperthyroidism.

PubMed

Ang, Lynn P; Avram, Anca M; Lieberman, Richard W; Esfandiari, Nazanene H

2017-06-01

We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii. This case illustrates the advantage of fusion SPECT/CT imaging with planar I-WBS for diagnosis of extrathyroidal thyrotoxicosis.

Diverse bone scan abnormalitites in "shin splints".

PubMed

Spencer, R P; Levinson, E D; Baldwin, R D; Sziklas, J J; Witek, J T; Rosenberg, R

1979-12-01

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of the foot.

Ga-67 citrate myocardial uptake in a patient with AIDS, toxoplasmosis, and myocarditis

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

Memel, D.S.; DeRogatis, A.J.; William, D.C.

1991-05-01

A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis.

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

Galatola, G.; Jazrawi, R.P.; Bridges, C.

/sup 75/Se-homocholic acid-taurine (/sup 75/SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for /sup 75/SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, (/sup 14/C)cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for /sup 75/SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6%more » vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for /sup 75/SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for /sup 75/SeHCAT (14.3% and 1.5% dose/min) than for (/sup 14/C)cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (2/sup 75/ vs. 670 ml/min). In vitro, /sup 75/SeHCAT was bound to serum proteins more completely than (/sup 14/C)cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that /sup 75/SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as (/sup 14/C)cholic acid-taurine, probably due to its stronger protein binding. The clinical value of /sup 75/SeHCAT in assessing liver disease should be investigated.« less

HIV policy and implementation: a national policy review and an implementation case study of a rural area of northern Malawi.

PubMed

Dasgupta, Aisha N Z; Wringe, Alison; Crampin, Amelia C; Chisambo, Christina; Koole, Olivier; Makombe, Simon; Sungani, Charles; Todd, Jim; Church, Kathryn

2016-09-01

Malawi is a global leader in the design and implementation of progressive HIV policies. However, there continues to be substantial attrition of people living with HIV across the "cascade" of HIV services from diagnosis to treatment, and program outcomes could improve further. Ability to successfully implement national HIV policy, especially in rural areas, may have an impact on consistency of service uptake. We reviewed Malawian policies and guidelines published between 2003 and 2013 relating to accessibility of adult HIV testing, prevention of mother-to-child transmission and HIV care and treatment services using a policy extraction tool, with gaps completed through key informant interviews. A health facility survey was conducted in six facilities serving the population of a demographic surveillance site in rural northern Malawi to investigate service-level policy implementation. Survey data were analyzed using descriptive statistics. Policy implementation was assessed by comparing policy content and facility practice using pre-defined indicators covering service access: quality of care, service coordination and patient tracking, patient support, and medical management. ART was rolled out in Malawi in 2004 and became available in the study area in 2005. In most areas, practices in the surveyed health facilities complied with or exceeded national policy, including those designed to promote rapid initiation onto treatment, such as free services and task-shifting for treatment initiation. However, policy and/or practice were/was lacking in certain areas, in particular those strategies to promote retention in HIV care (e.g., adherence monitoring and home-based care). In some instances, though, facilities implemented alternative progressive practices aimed at improving quality of care and encouraging adherence. While Malawi has formulated a range of progressive policies aiming to promote rapid initiation onto ART, increased investment in policy implementation strategies and quality service delivery, in particular to promote long-term retention on treatment may improve outcomes further.

Usefulness of 3'-[F-18]fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy.

PubMed

Pio, Betty S; Park, Cecilia K; Pietras, Richard; Hsueh, Wei-Ann; Satyamurthy, Nagichettiar; Pegram, Mark D; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

2006-01-01

The usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) in monitoring breast cancer response to chemotherapy has previously been reported. Elevated uptake of FDG by treated tumors can persist however, particularly in the early period after treatment is initiated. 3'-[F-18]Fluoro-3'-deoxythymidine (FLT) has been developed as a marker for cellular proliferation and, in principle, could be a more accurate predictor of the long-term effect of chemotherapy on tumor viability. We examined side-by-side FDG and FLT imaging for monitoring and predicting tumor response to chemotherapy. Fourteen patients with newly diagnosed primary or metastatic breast cancer, who were about to commence a new pharmacologic treatment regimen, were prospectively studied. Dynamic 3-D PET imaging of uptake into a field of view centered over tumor began immediately after administration of FDG or FLT (150 MBq). After 45 minutes of dynamic acquisition, a clinically standard whole-body PET scan was acquired. Patients were scanned with both tracers on two separate days within one week of each other (1) before beginning treatment, (2) two weeks following the end of the first cycle of the new regimen, and (3) following the final cycle of that regimen, or one year after the initial PET scans, whichever came first. (Median and mean times of early scans were 5.0 and 6.6 weeks after treatment initiation; median and mean times for late scans were 26.0 and 30.6 weeks after treatment initiation.) Scan data were analyzed on both tumor-by-tumor and patient-by-patient bases, and compared to each patient's clinical course. Mean change in FLT uptake in primary and metastatic tumors after the first course of chemotherapy showed a significant correlation with late (av. interval 5.8 months) changes in CA27.29 tumor marker levels (r = 0.79, P = 0.001). When comparing changes in tracer uptake after one chemotherapy course versus late changes in tumor size as measured by CT scans, FLT was again a good predictor of eventual tumor response (r = 0.74, P = 0.01). Tumor uptake of FLT was near-maximal by 10 minutes after injection. The time frame five to 10 minutes postinjection of FLT produced standardized uptake value (SUV) values highly correlated with SUV values obtained after 45-minute uptake (r = 0.83, P < 0.0001), and changes in these early SUVs after the first course of chemotherapy correlated with late changes in CA27.29 (r = 0.93, P = 0.003). A 10-minute FLT-PET scan acquired two weeks after the end of the first course of chemotherapy is useful for predicting longer-term efficacy of chemotherapy regimens for women with breast cancer.

The Correlation of the Initial Rate of I131 Uptake in the Thyroid with the Clinical Evaluation of the Thyroid Function,

DTIC Science & Technology

1950-10-01

the need for definitive treatment of the patient suspected of having hyperthyroidism . These studies are time-consuming. At the suggestion of A.V.H in...curve in differentiating the normal from the hyperthyroid patient. The rate of uptake of I131 in the thyroid during the interval of a few hours after

A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model

PubMed Central

Perry, Steve F.

2016-01-01

The effects of acute exposure to acidic water on Na+ and Cl− homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio. Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na+ uptake and whole body Na+ content. Nevertheless, the capacity for Na+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na+ enrichment after preexposure to acidic water: H+-ATPase rich (HR) cells, which coexpress the Na+/H+ exchanger isoform 3b (NHE3b), and a non-HR cell population. In fish experiencing Na+-Cl− cotransporter (NCC) knockdown, we observed no Sodium Green accumulation in the latter cell type, suggesting the non-HR cells were NCC cells. Elimination of NHE3b-expressing HR cells did not prevent the increased Na+ uptake following acid exposure. On the other hand, the increased Na+ uptake was abolished when the acidic water was enriched with Na+ and Cl−, but not with Na+ only, indicating that the elevated Na+ uptake after acid exposure was associated with the compensatory regulation of Cl−. Further examinations demonstrated that acute acid exposure also reduced whole body Cl− levels and increased the capacity for Cl− uptake. Moreover, knockdown of NCC prevented the increased uptake of both Na+ and Cl− after exposure to acidic water. Together, the results of the present study revealed a novel role of NCC in the compensatory regulation of Na+ and Cl− uptake following acute acidosis. PMID:27784676

Uptake of lactosylated low-density lipoprotein by galactose-specific receptors in rat liver.

PubMed

Bijsterbosch, M K; Van Berkel, T J

1990-08-15

The liver contains two types of galactose receptors, specific for Kupffer and parenchymal cells respectively. These receptors are only expressed in the liver, and therefore are attractive targets for the specific delivery of drugs. We provided low-density lipoprotein (LDL), a particle with a diameter of 23 nm in which a variety of drugs can be incorporated, with terminal galactose residues by lactosylation. Radioiodinated LDL, lactosylated to various extents (60-400 mol of lactose/ mol of LDL), was injected into rats. The plasma clearance and hepatic uptake of radioactivity were correlated with the extent of lactosylation. Highly lactosylated LDL (greater than 300 lactose/LDL) is completely cleared from the blood by liver within 10 min. Pre-injection with N-acetylgalactosamine blocks liver uptake, which indicates that the hepatic recognition sites are galactose-specific. The hepatic uptake occurs mainly by parenchymal and Kupffer cells. At a low degree of lactosylation, approx. 60 lactose/LDL, the specific uptake (ng/mg of cell protein) is 28 times higher in Kupffer cells than in parenchymal cells. However, because of their much larger mass, parenchymal cells are the main site of uptake. At high degrees of lactosylation (greater than 300 lactose/LDL), the specific uptake in Kupffer cells is 70-95 times that in parenchymal cells. Under these conditions, Kupffer cells are, despite their much smaller mass, the main site of uptake. Thus not only the size but also the surface density of galactose on lactosylated LDL is important for the balance of uptake between Kupffer and parenchymal cells. This knowledge should allow us to design particulate galactose-bearing carriers for the rapid transport of various drugs to either parenchymal cells or Kupffer cells.

Barrier dysfunction and bacterial uptake in the follicle-associated epithelium of ileal Crohn's disease.

PubMed

Keita, Asa V; Söderholm, Johan D

2012-07-01

The ability to control uptake across the mucosa and protect from harmful substances in the gut lumen is defined as intestinal barrier function. The etiology of Crohn's disease is unknown, but genetic, environmental, and immunological factors all contribute. The frontline between these factors lies in the intestinal barrier. The most important inflammation-driving environmental factor in Crohn's disease is the microbiota, where Esherichia coli strains have been assigned a key role. The first observable signs of Crohn's disease are small aphtoid ulcers over Peyer's patches and lymphoid follicles. The overlaying follicle-associated epithelium (FAE) is specialized for luminal sampling and is an entry site for antigens and bacteria. We have demonstrated increased E. coli uptake across the FAE in Crohn's disease, which may initiate inflammation. This short review will discuss barrier dysfunction and bacteria in the context of ileal Crohn's disease, and how the FAE might be the site of initial inflammation. © 2012 New York Academy of Sciences.

EFFECT, UPTAKE AND DISPOSITION OF NITROBENZENE IN SEVERAL TERRESTRIAL PLANTS

EPA Science Inventory

Eight species of plants were exposed to nitrobenzene in a hydroponic solution. our species experienced no depression of either transpiration or photosynthetic rates, while one was rapidly killed and the other three were temporarily affected but recovered from the treatment. ptake...

Anthropogenic chemicals as drivers of change for coastal ecosystems: wetlands, mangroves and seagrass habitats.

EPA Science Inventory

Coastal wetlands, mangrove and seagrass habitats are rapidly declining worldwide which reduces their many ecological services. This presentation summarizes the results of a literature survey conducted to determine scientific understanding of contaminant uptake and toxicity of non...

Rapid phenotyping of alfalfa root system architecture

USDA-ARS?s Scientific Manuscript database

Root system architecture (RSA) influences the capacity of an alfalfa plant for symbiotic nitrogen fixation, nutrient uptake and water use efficiency, resistance to frost heaving, winterhardiness, and some pest and pathogen resistance. However, we currently lack a basic understanding of root system d...

Foliar uptake of cesium from the water column by aquatic macrophytes.

PubMed

Pinder, J E; Hinton, T G; Whicker, F W

2006-01-01

The probable occurrence and rate of foliar absorption of stable cesium (133Cs) from the water column by aquatic macrophyte species was analyzed following the addition of 133Cs into a small reservoir near Aiken, South Carolina, USA. An uptake parameter u (10(3)Lkg(-1)d(-1)) and a loss rate parameter k (d(-1)) were estimated for each species using time series of 133Cs concentrations in the water and plant tissues. Foliar uptake, as indicated by rapid increases in plant concentrations following the 133Cs addition, occurred in two floating-leaf species, Brasenia schreberi and Nymphaea odorata, and two submerged species, Myriophyllum spicatum and Utricularia inflata. These species had values of u> or =0.75 x 10(3)Lkg(-1)d(-1). Less evidence for foliar uptake was observed in three emergent species, including Typha latifolia. Ratios of u to k for B. schreberi, M. spicatum, N. odorata and U. inflata can be used to estimate concentration ratios (CR) at equilibrium, and these estimates were generally within a factor of 2 of the CR for 137Cs for these species in the same reservoir. This correspondence suggests that foliar uptake of Cs was the principal absorption mechanism for these species. Assessments of: (1) the prevalence of foliar uptake of potassium, rubidium and Cs isotopes by aquatic macrophytes and (2) the possible importance of foliar uptake of Cs in other lentic systems are made from a review of foliar uptake studies and estimation of comparable u and k values from lake studies involving Cs releases.

Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

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

Hartvig, P.; Bergstroem, K.; Lindberg, B.

1984-07-01

The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appearedmore » 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.« less

Effectiveness of using thyrocalcitonin for the prevention of a calcium metabolic disorder in the mineralized tissues of rabbits with 30 days hypokinesia

NASA Technical Reports Server (NTRS)

Volozhin, A. I.; Shashkov, V. S.; Dmitriyev, B. S.; Yegorov, B. B.; Lobachik, V. I.; Brishin, A. I.

1980-01-01

A 30 day hypokinesia in rabbits led to a considerable lag in weight gain for the skeletal bones, reduction in Ca45 uptake, and an increase in isotope resorption rate in the rapidly metabolized fraction of extremity bones. On the other hand, Ca45 content in the teeth and maxillae increased, which may be explained by redistribution of isotope among the various mineralized tissues. Injection of thyrocalcitonin (50 IU/day) produced a distinct normalizing effect on Ca45 uptake and resorption in the mineralized tissues of rabbits kept hypokinetic.

The African American Women and Mass Media (AAMM) campaign in Georgia: quantifying community response to a CDC pilot campaign

PubMed Central

Johnson-Turbes, Ashani; Berkowitz, Zahava; Zavahir, Yasmine

2015-01-01

Purpose To evaluate whether a culturally appropriate campaign using “Black radio” and print media increased awareness and utilization of local mammography screening services provided by the Centers for Disease Control and Prevention’s National Breast and Cervical Cancer Early Detection Program among African American women. Methods The evaluation used a quasi-experimental design involving data collection during and after campaign implementation in two intervention sites in GA (Savannah with radio and print media and Macon with radio only) and one comparison site (Columbus, GA). We used descriptive statistics to compare mammography uptake for African American women during the initial months of the campaign (8/08–1/09) with the latter months (2/09–8/09) and a post-campaign (9/09–12/09) period in each of the study sites. Comparisons of monthly mammogram uptake between cities were performed with multinomial logistic regression. We assumed a p value <0.05 to be significant. Results We observed an increase of 46 and 20 % in Savannah and Macon, respectively, from the initial period of the campaign to the later period. However, the increase did not persist in the post-campaign period. Analysis comparing monthly mammogram uptake in Savannah and Macon with Columbus showed a significant increase in uptake from the first to the second period in Savannah only (OR 1.269, 95 % CI (1.005–1.602), p = 0.0449). Conclusions Dissemination of health promotion messages via a culturally appropriate, multicomponent campaign using Black radio and print media was effective in increasing mammogram uptake in Savannah among low-income, African American women. Additional research is needed to quantify the relative contribution of campaign radio, print media, and community components to sustain increased mammography uptake. PMID:25732344

Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum.

PubMed

Niemand, J; Louw, A I; Birkholtz, L; Kirk, K

2012-09-01

Polyamines and the enzymes involved in their biosynthesis are present at high levels in rapidly proliferating cells, including cancer cells and protozoan parasites. Inhibition of polyamine biosynthesis in asexual blood-stage malaria parasites causes cytostatic arrest of parasite development under in vitro conditions, but does not cure infections in vivo. This may be due to replenishment of the parasite's intracellular polyamine pool via salvage of exogenous polyamines from the host. However, the mechanism(s) of polyamine uptake by the intraerythrocytic parasite are not well understood. In this study, the uptake of the polyamines, putrescine and spermidine, into Plasmodium falciparum parasites functionally isolated from their host erythrocyte was investigated using radioisotope flux techniques. Both putrescine and spermidine were taken up into isolated parasites via a temperature-dependent process that showed cross-competition between different polyamines. There was also some inhibition of polyamine uptake by basic amino acids. Inhibition of polyamine biosynthesis led to an increase in the total amount of putrescine and spermidine taken up from the extracellular medium. The uptake of putrescine and spermidine by isolated parasites was independent of extracellular Na(+) but increased with increasing external pH. Uptake also showed a marked dependence on the parasite's membrane potential, decreasing with membrane depolarization and increasing with membrane hyperpolarization. The data are consistent with polyamines being taken up into the parasite via an electrogenic uptake process, energised by the parasite's inwardly negative membrane potential. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

A Novel ¹¹¹In-Labeled Anti-Prostate-Specific Membrane Antigen Nanobody for Targeted SPECT/CT Imaging of Prostate Cancer.

PubMed

Chatalic, Kristell L S; Veldhoven-Zweistra, Joke; Bolkestein, Michiel; Hoeben, Sander; Koning, Gerben A; Boerman, Otto C; de Jong, Marion; van Weerden, Wytske M

2015-07-01

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer (PCa) and a promising target for molecular imaging and therapy. Nanobodies (single-domain antibodies, VHH) are the smallest antibody-based fragments possessing ideal molecular imaging properties, such as high target specificity and rapid background clearance. We developed a novel anti-PSMA Nanobody (JVZ-007) for targeted imaging and therapy of PCa. Here, we report on the application of the (111)In-radiolabeled Nanobody for SPECT/CT imaging of PCa. A Nanobody library was generated by immunization of a llama with 4 human PCa cell lines. Anti-PSMA Nanobodies were captured by biopanning on PSMA-overexpressing cells. JVZ-007 was selected for evaluation as an imaging probe. JVZ-007 was initially produced with a c-myc-hexahistidine (his) tag allowing purification and detection. The c-myc-his tag was subsequently replaced by a single cysteine at the C terminus, allowing site-specific conjugation of chelates for radiolabeling. JVZ-007-c-myc-his was conjugated to 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (p-SCN-DTPA) via the lysines, whereas JVZ-007-cys was conjugated to maleimide-DTPA via the C-terminal cysteine. PSMA targeting was analyzed in vitro by cell-binding experiments using flow cytometry, autoradiography, and internalization assays with various PCa cell lines and patient-derived xenografts (PDXs). The targeting properties of radiolabeled Nanobodies were evaluated in vivo in biodistribution and SPECT/CT imaging experiments, using nude mice bearing PSMA-positive PC-310 and PSMA-negative PC-3 tumors. JVZ-007 was successfully conjugated to DTPA for radiolabeling with (111)In at room temperature. (111)In-JVZ007-c-myc-his and (111)In-JVZ007-cys internalized in LNCaP cells and bound to PSMA-expressing PDXs and, importantly, not to PSMA-negative PDXs and human kidneys. Good tumor targeting and fast blood clearance were observed for (111)In-JVZ-007-c-myc-his and (111)In-JVZ-007-cys. Renal uptake of (111)In-JVZ-007-c-myc-his was initially high but was efficiently reduced by coinjection of gelofusine and lysine. The replacement of the c-myc-his tag by the cysteine contributed to a further reduction of renal uptake without loss of targeting. PC-310 tumors were clearly visualized by SPECT/CT with both tracers, with low renal uptake (<4 percentage injected dose per gram) for (111)In-JVZ-007-cys already at 3 h after injection. We developed an (111)In-radiolabeled anti-PSMA Nanobody, showing good tumor targeting, low uptake in nontarget tissues, and low renal retention, allowing excellent SPECT/CT imaging of PCa within a few hours after injection. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A five-year study of the impact of nitrogen addition on methane uptake in alpine grassland.

PubMed

Yue, Ping; Li, Kaihui; Gong, Yanming; Hu, Yukun; Mohammat, Anwar; Christie, Peter; Liu, Xuejun

2016-08-30

It remains unclear how nitrogen (N) deposition affects soil methane (CH4) uptake in semiarid and arid zones. An in situ field experiment was conducted from 2010 to 2014 to systematically study the effect of various N application rates (0, 10, 30, and 90 kg N ha(-1) yr(-1)) on CH4 flux in alpine grassland in the Tianshan Mountains. No significant influence of N addition on CH4 uptake was found. Initially the CH4 uptake rate increased with increasing N application rate by up to 11.5% in 2011 and then there was gradual inhibition by 2014. However, the between-year variability in CH4 uptake was very highly significant with average uptake ranging from 52.9 to 106.6 μg C m(-2) h(-1) and the rate depended largely on seasonal variability in precipitation and temperature. CH4 uptake was positively correlated with soil temperature, air temperature and to a lesser extent with precipitation, and was negatively correlated with soil moisture and NO3(-)-N content. The results indicate that between-year variability in CH4 uptake was impacted by precipitation and temperature and was not sensitive to elevated N deposition in alpine grassland.

A five-year study of the impact of nitrogen addition on methane uptake in alpine grassland

PubMed Central

Yue, Ping; Li, Kaihui; Gong, Yanming; Hu, Yukun; Mohammat, Anwar; Christie, Peter; Liu, Xuejun

2016-01-01

It remains unclear how nitrogen (N) deposition affects soil methane (CH4) uptake in semiarid and arid zones. An in situ field experiment was conducted from 2010 to 2014 to systematically study the effect of various N application rates (0, 10, 30, and 90 kg N ha−1 yr−1) on CH4 flux in alpine grassland in the Tianshan Mountains. No significant influence of N addition on CH4 uptake was found. Initially the CH4 uptake rate increased with increasing N application rate by up to 11.5% in 2011 and then there was gradual inhibition by 2014. However, the between-year variability in CH4 uptake was very highly significant with average uptake ranging from 52.9 to 106.6 μg C m−2 h−1 and the rate depended largely on seasonal variability in precipitation and temperature. CH4 uptake was positively correlated with soil temperature, air temperature and to a lesser extent with precipitation, and was negatively correlated with soil moisture and NO3−-N content. The results indicate that between-year variability in CH4 uptake was impacted by precipitation and temperature and was not sensitive to elevated N deposition in alpine grassland. PMID:27571892

The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria.

PubMed

Buntinas, L; Gunter, K K; Sparagna, G C; Gunter, T E

2001-04-02

A mechanism of Ca(2+) uptake, capable of sequestering significant amounts of Ca(2+) from cytosolic Ca(2+) pulses, has previously been identified in liver mitochondria. This mechanism, the Rapid Mode of Ca(2+) uptake (RaM), was shown to sequester Ca(2+) very rapidly at the beginning of each pulse in a sequence [Sparagna et al. (1995) J. Biol. Chem. 270, 27510-27515]. The existence and properties of RaM in heart mitochondria, however, are unknown and are the basis for this study. We show that RaM functions in heart mitochondria with some of the characteristics of RaM in liver, but its activation and inhibition are quite different. It is feasible that these differences represent different physiological adaptations in these two tissues. In both tissues, RaM is highly conductive at the beginning of a Ca(2+) pulse, but is inhibited by the rising [Ca(2+)] of the pulse itself. In heart mitochondria, the time required at low [Ca(2+)] to reestablish high Ca(2+) conductivity via RaM i.e. the 'resetting time' of RaM is much longer than in liver. RaM in liver mitochondria is strongly activated by spermine, activated by ATP or GTP and unaffected by ADP and AMP. In heart, RaM is activated much less strongly by spermine and unaffected by ATP or GTP. RaM in heart is strongly inhibited by AMP and has a biphasic response to ADP; it is activated at low concentrations and inhibited at high concentrations. Finally, an hypothesis consistent with the data and characteristics of liver and heart is presented to explain how RaM may function to control the rate of oxidative phosphorylation in each tissue. Under this hypothesis, RaM functions to create a brief, high free Ca(2+) concentration inside mitochondria which may activate intramitochondrial metabolic reactions with relatively small amounts of Ca(2+) uptake. This hypothesis is consistent with the view that intramitochondrial [Ca(2+)] may be used to control the rate of ADP phosphorylation in such a way as to minimize the probability of activating the Ca(2+)-induced mitochondrial membrane permeability transition (MPT).

Active caspase-1 induces plasma membrane pores that precede pyroptotic lysis and are blocked by lanthanides#

PubMed Central

Russo, Hana M.; Rathkey, Joseph; Boyd-Tressler, Andrea; Katsnelson, Michael A.; Abbott, Derek W.; Dubyak, George R.

2016-01-01

Canonical inflammasome activation induces a caspase-1/gasdermin D (Gsdmd) dependent lytic cell death called pyroptosis which promotes anti-microbial host defense but may contribute to sepsis. The nature of the caspase-1-dependent change in plasma membrane (PM) permeability during pyroptotic progression remains incompletely defined. We assayed propidium2+ (Pro2+) influx kinetics during NLRP3 or Pyrin inflammasome activation in murine bone marrow-derived macrophages (BMDM) as an indicator of this PM permeabilization. BMDM were characterized by rapid Pro2+ influx after initiation of NLRP3 or Pyrin inflammasomes by nigericin or C. difficile toxin B (TcdB), respectively. No Pro2+ uptake in response to nigericin or TcdB was observed in Caspase-1−/− or ASC−/− BMDM. The cytoprotectant glycine profoundly suppressed nigericin and TcdB-induced lysis but not Pro2+ influx. The absence of Gsdmd expression resulted in suppression of nigericin-stimulated Pro2+ influx and pyroptotic lysis. Extracellular La3+ and Gd3+ rapidly and reversibly blocked the induced Pro2+ influx and markedly delayed pyroptotic lysis without limiting upstream inflammasome assembly and caspase-1 activation. Thus, caspase-1 driven pyroptosis requires induction of initial pre-lytic pores in the PM that are dependent on Gsdmd expression. These PM pores also facilitated the efflux of cytosolic ATP and influx of extracellular Ca2+. Although lanthanides and Gsdmd deletion both suppressed PM pore activity and pyroptotic lysis, robust IL-1β release was observed in lanthanide-treated BMDM but not in Gsdmd-deficient cells. This suggests roles for Gsdmd in both passive IL-1β release secondary to pyroptotic lysis and in non-lytic/non-classical IL-1β export. PMID:27385778

Fluorescent aromatic hydrocarbons in bile as a biomarker of exposure of brown bullheads (Ameiurus nebulosus) to contaminated sediments

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

Leadly, T.A.; Haffner, G.D.; Arcand-Hoy, L.D.

1999-04-01

Analysis of fluorescent aromatic compounds (FACs) in the bile of fish has been widely used as a biomarker of exposure to polynuclear aromatic hydrocarbon (PAH) contamination. However, bile FAC data for feral fish populations are typically highly variable, and in a few cases, elevation of FACs has not been observed in fish from contaminated areas. In this study, the bile FACs and hepatic ethoxyresorufin-O-deethylase activity in brown bullheads (Ameiurus nebulosus) exposed in the laboratory to contaminated sediments from Hamilton Harbour, Ontario, Canada, increased by 173-fold within 72 h of initial exposure and rapidly declined thereafter. In bullheads caged in themore » contaminated Trenton Channel area of the Detroit River, bile FACs also increased rapidly within 4 d of initial exposure to mean levels >3,000 ng of benzo[a]pyrene equivalents per milliliter of bile. Surprisingly, there was no difference in the mean-levels of bile FACs in fish caged above the sediment versus fish caged in direct contact with the sediment, indicating that water may be the major vector for uptake of PAHs. The lower bile FACs in bullheads caged in other regions of the Detroit River were consistent with the lower concentrations of PAHs in the sediments from these areas. These data indicate that bile FAC levels are a biomarker of recent exposure to aromatic hydrocarbons in sediments. However, FAC data were highly variable even in these studies, in which fish were relatively homogenous in size, feeding status, and exposure history. Therefore, Even higher variability in bile FAC data are expected in biomarker studies as a result of differences in reproductive status, size, diet, and mobility of the fish.« less

The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism.

PubMed

Cisternas, Pedro; Silva-Alvarez, Carmen; Martínez, Fernando; Fernandez, Emilio; Ferrada, Luciano; Oyarce, Karina; Salazar, Katterine; Bolaños, Juan P; Nualart, Francisco

2014-05-01

Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time- and dose-dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes. © 2014 International Society for Neurochemistry.

Intracellular putrescine and spermidine deprivation induces increased uptake of the natural polyamines and methylglyoxal bis(guanylhydrazone).

PubMed Central

Alhonen-Hongisto, L; Seppänen, P; Jänne, J

1980-01-01

Inhibition of polyamine synthesis by alpha-difluoromethylornithine in cultured Ehrlich ascites-carcinoma cells rapidly enhanced the uptake of exogenous putrescine, spermidine and spermine from the culture medium. In tumour cells exposed to the drug for 2 days, the intracellular concentration of spermidine was decreased to less than 10% of that found in untreated cells. However, the strikingly stimulated transport system brought the concentration of spermidine to the control values in less than 2h after supplementation of the cells with micromolar concentrations of the polyamine. In the absence of polyamine deprivation, tumour cells did not accumulate extracellular polyamines to any appreciable extent. Ascites-tumour cells deprived of putrescine and spermidine likewise concentrated methylglyoxal bis(guanylhydrazone) [1,1'-[methylethanedylidine)dinitrilo]diguanidine] at a greatly enhanced rate. A previous "priming of tumour cells with difluoromethylornithine followed by an exposure of the cells to methylglyoxal bis(guanylhydrazone) resulted in a marked and rapid anti-proliferative effect. PMID:6786285

Arsenate adsorption mechanisms at the allophane - Water interface

USGS Publications Warehouse

Arai, Y.; Sparks, D.L.; Davis, J.A.

2005-01-01

We investigated arsenate (As(V)) reactivity and surface speciation on amorphous aluminosilicate mineral (synthetic allophane) surfaces using batch adsorption experiments, powder X-ray diffraction (XRD), and X-ray absorption spectroscopy (XAS). The adsorption isotherm experiments indicated that As(V) uptake increased with increasing [As(V)]0 from 50 to 1000 ??M (i.e., Langmuir type adsorption isotherm) and that the total As adsorption slightly decreased with increasing NaCl concentrations from 0.01 to 0.1 M. Arsenate adsorption was initially (0-10 h) rapid followed by a slow continuum uptake, and the adsorption processes reached the steady state after 720 h. X-ray absorption spectroscopic analyses suggest that As(V) predominantly forms bidentate binuclear surface species on aluminum octahedral structures, and these species are stable up to 11 months. Solubility calculations and powder XRD analyses indicate no evidence of crystalline AI-As(V) precipitates in the experimental systems. Overall, macroscopic and spectroscopic evidence suggest that the As(V) adsorption mechanisms at the allophane-water interface are attributable to ligand exchange reactions between As(V) and surface-coordinated water molecules and hydroxyl and silicate ions. The research findings imply that dissolved tetrahedral oxyanions (e.g., H2PO42- and H2AsO42-) are readily retained on amorphous aluminosilicate minerals in aquifer and soils at near neutral pH. The innersphere adsorption mechanisms might be important in controlling dissolved arsenate and phosphate in amorphous aluminosilicate-rich low-temperature geochemical environments. ?? 2005 American Chemical Society.

Tumor Targeting and Pharmacokinetics of a Near-Infrared Fluorescent-Labeled δ-Opioid Receptor Antagonist Agent, Dmt-Tic-Cy5.

PubMed

Huynh, Amanda Shanks; Estrella, Veronica; Stark, Valerie E; Cohen, Allison S; Chen, Tingan; Casagni, Todd J; Josan, Jatinder S; Lloyd, Mark C; Johnson, Joseph; Kim, Jongphil; Hruby, Victor J; Vagner, Josef; Morse, David L

2016-02-01

Fluorescence molecular imaging can be employed for the development of novel cancer targeting agents. Herein, we investigated the pharmacokinetics (PK) and cellular uptake of Dmt-Tic-Cy5, a delta-opioid receptor (δOR) antagonist-fluorescent dye conjugate, as a tumor-targeting molecular imaging agent. δOR expression is observed normally in the CNS, and pathologically in some tumors, including lung liver and breast cancers. In vitro, in vivo, and ex vivo experiments were conducted to image and quantify the fluorescence signal associated with Dmt-Tic-Cy5 over time using in vitro and intravital fluorescence microscopy and small animal fluorescence imaging of tumor-bearing mice. We observed specific retention of Dmt-Tic-Cy5 in tumors with maximum uptake in δOR-expressing positive tumors at 3 h and observable persistence for >96 h; clearance from δOR nonexpressing negative tumors by 6 h; and systemic clearance from normal organs by 24 h. Live-cell and intravital fluorescence microscopy demonstrated that Dmt-Tic-Cy5 had sustained cell-surface binding lasting at least 24 h with gradual internalization over the initial 6 h following administration. Dmt-Tic-Cy5 is a δOR-targeted agent that exhibits long-lasting and specific signal in δOR-expressing tumors, is rapidly cleared from systemic circulation, and is not retained in non-δOR-expressing tissues. Hence, Dmt-Tic-Cy5 has potential as a fluorescent tumor imaging agent.

Clathrin-dependent entry and vesicle-mediated exocytosis define insulin transcytosis across microvascular endothelial cells

PubMed Central

Azizi, Paymon M.; Zyla, Roman E.; Guan, Sha; Wang, Changsen; Liu, Jun; Bolz, Steffen-Sebastian; Heit, Bryan; Klip, Amira; Lee, Warren L.

2015-01-01

Transport of insulin across the microvasculature is necessary to reach its target organs (e.g., adipose and muscle tissues) and is rate limiting in insulin action. Morphological evidence suggests that insulin enters endothelial cells of the microvasculature, and studies with large vessel–derived endothelial cells show insulin uptake; however, little is known about the actual transcytosis of insulin and how this occurs in the relevant microvascular endothelial cells. We report an approach to study insulin transcytosis across individual, primary human adipose microvascular endothelial cells (HAMECs), involving insulin uptake followed by vesicle-mediated exocytosis visualized by total internal reflection fluorescence microscopy. In this setting, fluorophore-conjugated insulin exocytosis depended on its initial binding and uptake, which was saturable and much greater than in muscle cells. Unlike its degradation within muscle cells, insulin was stable within HAMECs and escaped lysosomal colocalization. Insulin transcytosis required dynamin but was unaffected by caveolin-1 knockdown or cholesterol depletion. Instead, insulin transcytosis was significantly inhibited by the clathrin-mediated endocytosis inhibitor Pitstop 2 or siRNA-mediated clathrin depletion. Accordingly, insulin internalized for 1 min in HAMECs colocalized with clathrin far more than with caveolin-1. This study constitutes the first evidence of vesicle-mediated insulin transcytosis and highlights that its initial uptake is clathrin dependent and caveolae independent. PMID:25540431

BELOWGROUND NITROGEN UPTAKE AND ALLOCATION ...

EPA Pesticide Factsheets

Anthropogenic nitrogen inputs coupled with rising sea level complicate predictions of marsh stability. As marsh stability is a function of its vegetation, it is important to understand the mechanisms that drive community dynamics. Many studies have examined aboveground dynamics and nutrient cycling, but few have studied the belowground uptake and allocation of nitrogen. Literature suggests that D. spicata may dominate the marsh platform in nutrient-rich conditions, though the mechanism driving the vegetation shift is unclear. Our study examines belowground nutrient uptake and allocation underlying these patterns. To determine whether D. spicata is a more efficient scavenger of nutrients than S. alterniflora we performed a 15N pulse-chase experiment. Tracer was added to mesocosms growing D. spicata and S. alterniflora in monoculture. After the initial pulse, a subset of pots were sacrificed weekly and partitioned into detailed depth intervals for 15N analysis of several belowground pools: live coarse and fine roots, live rhizomes, dead organic matter, and bulk sediment. Comparisons between D. spicata and S. alterniflora uptake and allocation can explain mechanisms of competitive advantage and predictions of D. spicata dominance. Additionally, we used denitrification enzyme assays (DEA) and greenhouse gas slurries to quantify denitrification rates and potentials. Initial results suggest that the vegetation types support similar N-relevant microbial communities. Th

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

PubMed

Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

2015-01-01

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

Sorption-reduction coupled gold recovery process boosted by Pycnoporus sanguineus biomass: Uptake pattern and performance enhancement via biomass surface modification.

PubMed

Shi, Chaohong; Zhu, Nengwu; Kang, Naixin; Wu, Pingxiao; Zhang, Xiaoping; Zhang, Yanhong

2017-09-01

Biorecovery is emerging as a promising process to retrieve gold from secondary resources. The present study aimed to explore the uptake pattern of Pycnoporus sanguineus biomass for gold, identify the effective functional groups in gold recovery process, and thus further intensify the process via microbial surface modification. Results showed that P. sanguineus biomass could effectively recover gold with the formation of highly crystal AuNPs without any exogeneous electron donor. Under the conditions of various initial gold concentrations (1.0, 2.0, and 3.0 mM), biomass dosage of 2.0 g/L, solution pH value of 4.0, and incubation temperature of 30°C, the uptake equilibrium established after 4, 8, and 12 h, respectively. The uptake process could be well described by pseudo-second order kinetics model (R 2  = 0.9988) and Langmuir isotherm model (R 2  = 0.9958). The maximum uptake capacity of P. sanguineus reached as high as 358.69 mg/g. Further analysis indicated that amino, carboxyl and hydroxyl groups positively contributed to the uptake process. Among them, amino group significantly favored the uptake of gold during recovery process. When P. sanguineus biomass was modified by introduction of amino group, the gold uptake process was successfully intensified by shortening the uptake period and enhancing the uptake capacity. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1314-1322, 2017. © 2017 American Institute of Chemical Engineers.

Compensatory Root Water Uptake of Overlapping Root Systems

NASA Astrophysics Data System (ADS)

Agee, E.; Ivanov, V. Y.; He, L.; Bisht, G.; Shahbaz, P.; Fatichi, S.; Gough, C. M.; Couvreur, V.; Matheny, A. M.; Bohrer, G.

2015-12-01

Land-surface models use simplified representations of root water uptake based on biomass distributions and empirical functions that constrain water uptake during unfavorable soil moisture conditions. These models fail to capture the observed hydraulic plasticity that allows plants to regulate root hydraulic conductivity and zones of active uptake based on local gradients. Recent developments in root water uptake modeling have sought to increase its mechanistic representation by bridging the gap between physically based microscopic models and computationally feasible macroscopic approaches. It remains to be demonstrated whether bulk parameterization of microscale characteristics (e.g., root system morphology and root conductivity) can improve process representation at the ecosystem scale. We employ the Couvreur method of microscopic uptake to yield macroscopic representation in a coupled soil-root model. Using a modified version of the PFLOTRAN model, which represents the 3-D physics of variably saturated soil, we model a one-hectare temperate forest stand under natural and synthetic climatic forcing. Our results show that as shallow soil layers dry, uptake at the tree and stand level shift to deeper soil layers, allowing the transpiration stream demanded by the atmosphere. We assess the potential capacity of the model to capture compensatory root water uptake. Further, the hydraulic plasticity of the root system is demonstrated by the quick response of uptake to rainfall pulses. These initial results indicate a promising direction for land surface models in which significant three-dimensional information from large root systems can be feasibly integrated into the forest scale simulations of root water uptake.

Osmotic regulation of myo-inositol uptake in primary astrocyte cultures.

PubMed

Isaacks, R E; Bender, A S; Kim, C Y; Prieto, N M; Norenberg, M D

1994-03-01

Uptake of myo-inositol by astrocytes in hypertonic medium (440 mosm/kg H2O) was increased near 3-fold after incubation for 24 hours, which continued for 72 hours, as compared with the uptake by cells cultured in isotonic medium (38 nmoles/mg protein). myo-Inositol uptake by astrocytes cultured in hypotonic medium (180 mosm/kg H2O) for periods up to 72 hours was reduced by 74% to 8 to 10 nmoles/mg protein. Astrocytes incubated in either hypotonic or hypertonic medium for 24 hours and then placed in isotonic medium reversed the initial down- or up-regulation of uptake. Activation of chronic RVD and RVI correlates with regulation of myo-inositol uptake. A 30 to 40 mosm/kg H2O deviation from physiological osmolality can influence myo-inositol homeostasis. The intracellular content of myo-inositol in astrocytes in isotonic medium was 25.6 +/- 1.3 micrograms/mg protein (28 mM). This level of myo-inositol is sufficient for this compound to function as an osmoregulator in primary astrocytes and it is likely to contribute to the maintenance of brain volume.

Simultaneous Simulations of Uptake in Plants and Leaching to Groundwater of Cadmium and Lead for Arable Land Amended with Compost or Farmyard Manure

PubMed Central

Legind, Charlotte N.; Rein, Arno; Serre, Jeanne; Brochier, Violaine; Haudin, Claire-Sophie; Cambier, Philippe; Houot, Sabine; Trapp, Stefan

2012-01-01

The water budget of soil, the uptake in plants and the leaching to groundwater of cadmium (Cd) and lead (Pb) were simulated simultaneously using a physiological plant uptake model and a tipping buckets water and solute transport model for soil. Simulations were compared to results from a ten-year experimental field study, where four organic amendments were applied every second year. Predicted concentrations slightly decreased (Cd) or stagnated (Pb) in control soils, but increased in amended soils by about 10% (Cd) and 6% to 18% (Pb). Estimated plant uptake was lower in amended plots, due to an increase of Kd (dry soil to water partition coefficient). Predicted concentrations in plants were close to measured levels in plant residues (straw), but higher than measured concentrations in grains. Initially, Pb was mainly predicted to deposit from air into plants (82% in 1998); the next years, uptake from soil became dominating (30% from air in 2006), because of decreasing levels in air. For Cd, predicted uptake from air into plants was negligible (1–5%). PMID:23056555

Water uptake by growing cells: an assessment of the controlling roles of wall relaxation, solute uptake, and hydraulic conductance

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1993-01-01

Growing plant cells increase in volume principally by water uptake into the vacuole. There are only three general mechanisms by which a cell can modulate the process of water uptake: (a) by relaxing wall stress to reduce cell turgor pressure (thereby reducing cell water potential), (b) by modifying the solute content of the cell or its surroundings (likewise affecting water potential), and (c) by changing the hydraulic conductance of the water uptake pathway (this works only for cells remote from water potential equilibrium). Recent studies supporting each of these potential mechanisms are reviewed and critically assessed. The importance of solute uptake and hydraulic conductance is advocated by some recent studies, but the evidence is indirect and conclusions remain controversial. For most growing plant cells with substantial turgor pressure, it appears that reduction in cell turgor pressure, as a consequence of wall relaxation, serves as the major initiator and control point for plant cell enlargement. Two views of wall relaxation as a viscoelastic or a chemorheological process are compared and distinguished.

Development and Characterization of a 3D Printed, Keratin-Based Hydrogel.

PubMed

Placone, Jesse K; Navarro, Javier; Laslo, Gregory W; Lerman, Max J; Gabard, Alexis R; Herendeen, Gregory J; Falco, Erin E; Tomblyn, Seth; Burnett, Luke; Fisher, John P

2017-01-01

Keratin, a naturally-derived polymer derived from human hair, is physiologically biodegradable, provides adequate cell support, and can self-assemble or be crosslinked to form hydrogels. Nevertheless, it has had limited use in tissue engineering and has been mainly used as casted scaffolds for drug or growth factor delivery applications. Here, we present and assess a novel method for the printed, sequential production of 3D keratin scaffolds. Using a riboflavin-SPS-hydroquinone (initiator-catalyst-inhibitor) photosensitive solution we produced 3D keratin constructs via UV crosslinking in a lithography-based 3D printer. The hydrogels obtained have adequate printing resolution and result in compressive and dynamic mechanical properties, uptake and swelling capacities, cytotoxicity, and microstructural characteristics that are comparable or superior to those of casted keratin scaffolds previously reported. The novel keratin-based printing resin and printing methodology presented have the potential to impact future research by providing an avenue to rapidly and reproducibly manufacture patient-specific hydrogels for tissue engineering and regenerative medicine applications.

Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death

PubMed Central

Sanman, Laura E; Qian, Yu; Eisele, Nicholas A; Ng, Tessie M; van der Linden, Wouter A; Monack, Denise M; Weerapana, Eranthie; Bogyo, Matthew

2016-01-01

When innate immune cells such as macrophages are challenged with environmental stresses or infection by pathogens, they trigger the rapid assembly of multi-protein complexes called inflammasomes that are responsible for initiating pro-inflammatory responses and a form of cell death termed pyroptosis. We describe here the identification of an intracellular trigger of NLRP3-mediated inflammatory signaling, IL-1β production and pyroptosis in primed murine bone marrow-derived macrophages that is mediated by the disruption of glycolytic flux. This signal results from a drop of NADH levels and induction of mitochondrial ROS production and can be rescued by addition of products that restore NADH production. This signal is also important for host-cell response to the intracellular pathogen Salmonella typhimurium, which can disrupt metabolism by uptake of host-cell glucose. These results reveal an important inflammatory signaling network used by immune cells to sense metabolic dysfunction or infection by intracellular pathogens. DOI: http://dx.doi.org/10.7554/eLife.13663.001 PMID:27011353

Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells

PubMed Central

2015-01-01

Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond–drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers. PMID:25437772

Biosorption of copper(II) from aqueous solutions by green alga Cladophora fascicularis.

PubMed

Deng, Liping; Zhu, Xiaobin; Wang, Xinting; Su, Yingying; Su, Hua

2007-08-01

Biosorption is an effective means of removal of heavy metals from wastewater. In this work the biosorption behavior of Cladophora fascicularis was investigated as a function of pH, amount of biosorbent, initial Cu2+ concentration, temperature, and co-existing ions. Adsorption equilibria were well described by Langmuir isotherm models. The enthalpy change for the biosorption process was found to be 6.86 kJ mol(-1) by use of the Langmuir constant b. The biosorption process was found to be rapid in the first 30 min. The presence of co-existing cations such as Na+, K+, Mg2+, and Ca2+ and anions such as chloride, nitrate, sulfate, and acetate did not significantly affect uptake of Cu2+ whereas EDTA substantially affected adsorption of the metal. When experiments were performed with different desorbents the results indicated that EDTA was an efficient desorbent for the recovery of Cu2+ from biomass. IR spectral analysis suggested amido or hydroxy, C=O, and C-O could combine strongly with Cu2+.

Vapor annealing synthesis of non-epitaxial MgB2 films on glassy carbon

NASA Astrophysics Data System (ADS)

Baker, A. A.; Bayu Aji, L. B.; Bae, J. H.; Stavrou, E.; Steich, D. J.; McCall, S. K.; Kucheyev, S. O.

2018-05-01

We describe the fabrication and characterization of 25–800 nm thick MgB2 films on glassy carbon substrates by Mg vapor annealing of sputter-deposited amorphous B films. Results demonstrate a critical role of both the initial B film thickness and the temperature–time profile on the microstructure, elemental composition, and superconducting properties of the resultant MgB2 films. Films with thicknesses of 55 nm and below exhibit a smooth surface, with a roughness of 1.1 nm, while thicker films have surface morphology consisting of elongated nano-crystallites. The suppression of the superconducting transition temperature for thin films scales linearly with the oxygen impurity concentration and also correlates with the amount of lattice disorder probed by Raman scattering. The best results are obtained by a rapid (12 min) anneal at 850 °C with large temperature ramp and cooling rates of ∼540 °C min‑1. Such fast processing suppresses the deleterious oxygen uptake.

REAL-TIME INTRAVITAL IMAGING ESTABLISHES TUMOUR-ASSOCIATED MACROPHAGES AS THE EXTRASKELETAL TARGET OF BISPHOSPHONATE ACTION IN CANCER

PubMed Central

Junankar, Simon; Shay, Gemma; Jurczyluk, Julie; Ali, Naveid; Down, Jenny; Pocock, Nicholas; Parker, Andrew; Nguyen, Akira; Sun, Shuting; Kashemirov, Boris; McKenna, Charles E.; Croucher, Peter I.; Swarbrick, Alexander; Weilbaecher, Katherine; Phan, Tri Giang; Rogers, Michael J.

2014-01-01

Recent clinical trials have shown that bisphosphonate drugs improve breast cancer patient survival independent of their anti-resorptive effects on the skeleton. However, since bisphosphonates bind rapidly to bone mineral, the exact mechanisms of their anti-tumour action, particularly on cells outside of bone, remain unknown. Here we used real-time intravital two-photon microscopy to show extensive leakage of fluorescent bisphosphonate from the vasculature in 4T1 mouse mammary tumours, where it initially binds to areas of small, granular microcalcifications that are engulfed by tumour-associated macrophages (TAMs), but not tumour cells. Importantly, we also observed uptake of radiolabeled bisphosphonate in the primary breast tumour of a patient and showed the resected tumour to be infiltrated with TAMs and to contain similar granular microcalcifications. These data represent the first compelling in vivo evidence that bisphosphonates can target cells in tumours outside the skeleton and that their anti-tumour activity is likely to be mediated via TAMs. PMID:25312016

Fast-tracking implementation through trial design: the case of buprenorphine treatment in Victoria.

PubMed

Bammer, Gabriele; Ritter, Alison; Kutin, Jozica J; Lintzeris, Nicholas

2009-02-01

We investigated how a randomised controlled trial (RCT) could be designed to incorporate features known or thought likely to enhance the uptake of the new treatment into clinical practice post-trial. Between 1999 and 2001, we trialled buprenorphine treatment for heroin dependence in community settings throughout Victoria, using 28 experienced methadone prescribers and 34 pharmacists across 19 sites. In this case study, we describe how we incorporated seven features considered important in treatment uptake: skilled and experienced practitioners, government and policy support, incentives to prescribe the new treatment, specialist support services, clinical guidelines, training programs and patient involvement and information. We also present information showing that uptake of buprenorphine treatment was substantially boosted in Victoria compared with other Australian jurisdictions immediately after the trial in 2001 and that this increase was sustained until at least 2006. While we cannot prove that our trial design was responsible for the increased uptake of buprenorphine treatment in Victoria, we do show that design has been a neglected aspect of clinical trials in terms of enhancing post-trial uptake of the treatment being tested. Those interested in closing the 'know-do' gap between research and practice may wish to further explore this very promising lead. Imaginative linking of features known to enhance treatment uptake to pressing research questions may lead to new information on efficacy, as well as getting valuable drugs into the treatment system more rapidly.

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

PubMed

Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

2013-10-01

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

Diverse bone scan abnormalities in shin splints

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

Spencer, R.P.; Levinson, E.D.; Baldwin, R.D.

1979-12-01

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of themore » foot.« less

Effects of polyamine inhibitors on zinc uptake by COMMA-1D mammary epithelial cells

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

Allen, J.C.; Haedrich, L.H.

1991-03-15

Zn uptake or transport is stimulated by glucocorticoids in many types of epithelial cells, including the COMMA-1D mouse mammary cell line. The current objective was to determine whether polyamines also mediate glucocorticoid stimulation of Zn-uptake. Initially, cells grown in lactogenic hormone supplemented-media had approximately 65% greater {sup 65}Zn-uptake over 24 h than cells in nonsupplemented growth media (GM). {sup 65}Zn-uptake from HM with 10{sup {minus}5}M methylglyoxal-bis(guanylhydrazone) (MGBG) (s-adenosyl-methionine decarboxylase inhibitor to block polyamine synthesis) added was less than from GM. Exogenous spermidine added to the MGBG-HM media increased {sup 65}Zn-uptake. However, up to 10mM difluoromethylornithine (DFMO), a more specific inhibitormore » of sperimidine synthesis, had no significant effect on 24-h {sup 65}Zn-uptake by cells in HM. In GM, DFMO caused a slight dose-dependent decrease in {sup 65}Zn-uptake over the range 10{sup {minus}6} to 5 {times} 10{sup 3}M. Also, with 8 h of incubation, DFMO tended to decrease {sup 65}Zn-uptake in HM-stimulated cells. These data cannot yet distinguish between the possibilities that DFMO is inactivated during the 24-h incubation or that the dramatic effects of MGBG on {sup 65}Zn-uptake in these mammary-derived cells is not related to its inhibition of polyamine synthesis. Because COMMA-1D cells alter Zn uptake in response to lactogenic hormones and MGBG, the model system is suitable for further studies of the mechanisms of zinc transport in epithelia.« less

Recurrent Graves' hyperthyroidism after prolonged radioiodine-induced hypothyroidism.

PubMed

Salman, Fariha; Oktaei, Hooman; Solomon, Solomon; Nyenwe, Ebenezer

2017-07-01

Radioactive iodine (RAI) is the most cost effective therapy for Graves' disease (GD). Patients with GD who have become hypothyroid after therapeutic RAI, rarely develop recurrence of disease. Herein we describe a case of recurrence of thyrotoxicosis after 2 years of hypothyroidism. We present the clinical features, laboratory findings, imaging and management of an unusual case of recurrent hyperthyroidism. A 48-year-old male presented to the emergency room with a 2-day history of palpitation, chest discomfort and 30 pounds of weight loss. Examination was remarkable for rapid and irregular pulse, diffuse thyromegaly and brisk deep tendon reflexes but no eye changes or tremors. Laboratory tests showed thyroid-stimulating hormone (TSH) of <0.004 (0.3-5.6 mIU/ml), free thyroxine (FT4) 4.96 (0.9-1.8 ng/dl), free triiodothyronine (FT3) >20 (1.8-4.7 pg/ml), total thyroxine >800 (80-200 ng/dl). Electrocardiogram showed atrial fibrillation with rapid ventricular response. RAI uptake and scan showed a homogenous gland with 54% uptake in 6 h and 45% in 24 h. He was treated with propranolol and propylthiouracil with some clinical improvement. He subsequently underwent RAI therapy and developed hypothyroidism after 8 weeks. Hypothyroidism was treated with levothyroxine. At 2 years after RAI ablation, he again developed symptoms of hyperthyroidism and had suppressed TSH. The levothyroxine dose was stopped, 3 weeks after discontinuing levothyroxine, he remained hyperthyroid with TSH of 0.008 and FT4 of 1.62 and FT3 of 4.8. RAI uptake demonstrated 17% uptake at 24 h. Recurrent hyperthyroidism in GD is uncommon after development of post-ablative hypothyroidism. Our case illustrates the need for continued surveillance.

Healthcare providers' knowledge and attitudes about rapid tissue donation (RTD): phase one of establishing a rapid tissue donation programme in thoracic oncology.

PubMed

Schabath, Matthew B; McIntyre, Jessica; Pratt, Christie; Gonzalez, Luis E; Munoz-Antonia, Teresita; Haura, Eric B; Quinn, Gwendolyn P

2014-02-01

In preparation for the development of a rapid tissue donation (RTD) programme, we surveyed healthcare providers (HCPs) in our institution about knowledge and attitudes related to RTD with lung cancer patients. A 31-item web based survey was developed collecting data on demographics, knowledge and attitudes about RTD. The survey contained three items measuring participants' knowledge about RTD, five items assessing attitudes towards RTD recruitment and six items assessing HCPs' level of agreement with factors influencing decisions to discuss RTD. Response options were presented on a 5-point Likert scale. Ninety-one HCPs participated in the study. 66% indicated they had never heard of RTD prior to the survey, 78% rated knowledge of RTD as none or limited and 95.6% reported not having ethical or religious concerns about discussing RTD with patients. The majority were either not comfortable (17.8%) or not sure if they felt comfortable discussing RTD with cancer patients (42.2%). 56.1% indicated their knowledge of RTD would play an integral role in their decision to discuss RTD with patients. 71.4% reported concerns with RTD discussion and the emotional state of the patient. Physicians and nurses play an important role in initiating conversations about recruitment and donation to research that can ultimately influence uptake. Increasing HCP knowledge about RTD is a necessary step towards building an RTD programme. Our study provides important information about characteristics associated with low levels of knowledge and practice related to RTD where additional education and training may be warranted.

The compartmentation of phosphorylated thiamine derivatives in cultured neuroblastoma cells.

PubMed

Bettendorff, L

1994-05-26

Thiamine transport in cultured neuroblastoma cells is mediated by a high-affinity carrier (KM = 40 nM). In contrast, the uptake of the more hydrophobic sulbutiamine (isobutyrylthiamine disulfide) is unsaturable and its initial transport rate is 20-times faster than for thiamine. In the cytoplasm, sulbutiamine is rapidly hydrolyzed and reduced to free thiamine, the overall process resulting in a rapid and concentrative thiamine accumulation. Incorporation of radioactivity from [14C]thiamine or [14C]sulbutiamine into intracellular thiamine diphosphate is slow in both cases. Despite the fact that the diphosphate is probably the direct precursor for both thiamine monophosphate and triphosphate, the specific radioactivity increased much faster for the latter two compounds than for thiamine diphosphate. This suggests the existence of two pools of thiamine diphosphate, the larger one having a very slow turnover (about 17 h); a much smaller, rapidly turning over pool would be the precursor of thiamine mono- and triphosphate. The turnover time for thiamine triphosphate could be estimated to be 1-2 h. When preloading the cells with [14C]sulbutiamine was followed by a chase with the same concentration of the unlabeled compound, the specific radioactivities of thiamine and thiamine monophosphate decreased exponentially as expected, but labeling of the diphosphate continued to increase slowly. Specific radioactivity of thiamine triphosphate increased first, but after 30 min it began to slowly decrease. These results show for the first time the existence of distinct thiamine diphosphate pools in the same homogeneous cell population. They also suggest a complex compartmentation of thiamine metabolism.

Drought rapidly diminishes the large net CO2 uptake in 2011 over semi-arid Australia

PubMed Central

Ma, Xuanlong; Huete, Alfredo; Cleverly, James; Eamus, Derek; Chevallier, Frédéric; Joiner, Joanna; Poulter, Benjamin; Zhang, Yongguang; Guanter, Luis; Meyer, Wayne; Xie, Zunyi; Ponce-Campos, Guillermo

2016-01-01

Each year, terrestrial ecosystems absorb more than a quarter of the anthropogenic carbon emissions, termed as land carbon sink. An exceptionally large land carbon sink anomaly was recorded in 2011, of which more than half was attributed to Australia. However, the persistence and spatially attribution of this carbon sink remain largely unknown. Here we conducted an observation-based study to characterize the Australian land carbon sink through the novel coupling of satellite retrievals of atmospheric CO2 and photosynthesis and in-situ flux tower measures. We show the 2010–11 carbon sink was primarily ascribed to savannas and grasslands. When all biomes were normalized by rainfall, shrublands however, were most efficient in absorbing carbon. We found the 2010–11 net CO2 uptake was highly transient with rapid dissipation through drought. The size of the 2010–11 carbon sink over Australia (0.97 Pg) was reduced to 0.48 Pg in 2011–12, and was nearly eliminated in 2012–13 (0.08 Pg). We further report evidence of an earlier 2000–01 large net CO2 uptake, demonstrating a repetitive nature of this land carbon sink. Given a significant increasing trend in extreme wet year precipitation over Australia, we suggest that carbon sink episodes will exert greater future impacts on global carbon cycle. PMID:27886216

Fluorescent water-soluble perylenediimide-cored cationic dendrimers: synthesis, optical properties, and cell uptake.

PubMed

Xu, Zejun; He, Bicheng; Shen, Jie; Yang, Wantai; Yin, Meizhen

2013-05-07

Different generations of perylenediimide-cored dendrimers with peripheral amine groups were synthesized. All these water-soluble dendrimers could rapidly internalize into live cells with high efficacy of gene transfection and low cytotoxicity. Increasing dendrimer generation increased their ability for gene transfection.

HuPSON: the human physiology simulation ontology

PubMed Central

2013-01-01

Background Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. Results We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios. The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). Conclusions HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain. PMID:24267822

Residence times of reef-island sediments constrained by post-mortem precipitates

NASA Astrophysics Data System (ADS)

Mann, Thomas; Wizemann, André; Kench, Paul; Jompa, Jamaluddin; Westphal, Hildegard

2017-04-01

The precipitation of carbonate cements is a rapid process in tropical marine environments. Distinct from calcification, the onset of cementation coincides with the termination of 14C uptake within carbonate-sediment forming organisms. Here we show that this relationship presents new opportunities for examining the temporal lag between organism death and deposition in carbonate systems - the prerequisite for reliable depositional chronologies. We dated skeletal constituents collected from discretely stratified reef-island deposits in Indonesia. In each of the strata, internally least cemented segments of the calcifying green alga Halimeda yield the youngest ages. Complementary mesocosm experiments on cementation rates reveal that post-mortem cement growth initiates within months after transport commences. Continuous pore-filling cementation promptly stabilizes the initially fragile Halimeda skeleton. Furthermore, abrasion experiments show that such cementation significantly increases the durability of segments during transport. Implications of these findings are profound in two respects; first, evaluating residence times of skeletal carbonate constituents based on abrasion features is far from being adequate. Second, the absence of cements within sedimentary Halimeda segments signals that post-mortem transport through the intertidal zone occurred quasi-instantaneously. Radiometric ages from such specimens should minimize the temporal lag between organism death and deposition thus making them reliable indicators of sedimentation in supratidal environments.

The role of receptor topology in the vitamin D3 uptake and Ca{sup 2+} response systems

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

Morrill, Gene A., E-mail: gene.morrill@einstein.yu.edu; Kostellow, Adele B.; Gupta, Raj K.

The steroid hormone, vitamin D{sub 3}, regulates gene transcription via at least two receptors and initiates putative rapid response systems at the plasma membrane. The vitamin D receptor (VDR) binds vitamin D{sub 3} and a second receptor, importin-4, imports the VDR-vitamin D{sub 3} complex into the nucleus via nuclear pores. Here we present evidence that the Homo sapiens VDR homodimer contains two transmembrane (TM) helices ({sup 327}E – D{sup 342}), two TM “half-helix” ({sup 264}K − N{sup 276}), one or more large channels, and 16 cholesterol binding (CRAC/CARC) domains. The importin-4 monomer exhibits 3 pore-lining regions ({sup 226}E – L{supmore » 251}; {sup 768}V – G{sup 783}; {sup 876}S – A{sup 891}) and 16 CRAC/CARC domains. The MEMSAT algorithm indicates that VDR and importin-4 may not be restricted to cytoplasm and nucleus. VDR homodimer TM helix-topology predicts insertion into the plasma membrane, with two 84 residue C-terminal regions being extracellular. Similarly, MEMSAT predicts importin-4 insertion into the plasma membrane with 226 residue extracellular N-terminal regions and 96 residue C-terminal extracellular loops; with the pore-lining regions contributing gated Ca{sup 2+} channels. The PoreWalker algorithm indicates that, of the 427 residues in each VDR monomer, 91 line the largest channel, including two vitamin D{sub 3} binding sites and residues from both the TM helix and “half-helix”. Cholesterol-binding domains also extend into the channel within the ligand binding region. Programmed changes in bound cholesterol may regulate both membrane Ca{sup 2+} response systems and vitamin D{sub 3} uptake as well as receptor internalization by the endomembrane system culminating in uptake of the vitamin D{sub 3}-VDR-importin-4 complex into the nucleus.« less

Formation of Fe(III) oxyhydroxide colloids in freshwater and brackish seawater, with incorporation of phosphate and calcium

NASA Astrophysics Data System (ADS)

Gunnars, Anneli; Blomqvist, Sven; Johansson, Peter; Andersson, Christian

2002-03-01

The formation of Fe(III) oxyhydroxide colloids by oxidation of Fe(II) and their subsequent aggregation to larger particles were studied in laboratory experiments with natural water from a freshwater lake and a brackish coastal sea. Phosphate was incorporated in the solid phase during the course of hydrolysis of iron. The resulting precipitated amorphous Fe(III) oxyhydroxide phases were of varying composition, depending primarily on the initial dissolved Fe/P molar ratio, but with little influence by salinity or concentration of calcium ions. The lower limiting Fe/P ratio found for the solid phase suggests the formation of a basic Fe(III) phosphate compound with a stoichiometric Fe/P ratio of close to two. This implies that an Fe/P stoichiometry of ≈2 ultimately limits the capacity of precipitating Fe(III) to fix dissolved phosphate at oxic/anoxic boundaries in natural waters. In contrast to phosphorus, the uptake of calcium seemed to be controlled by sorption processes at the surface of the iron-rich particles formed. This uptake was more efficient in freshwater than in brackish water, suggesting that salinity restrains the uptake of calcium by newly formed Fe(III) oxyhydroxides in natural waters. Moreover, salinity enhanced the aggregation rate of the colloids formed. The suspensions were stabilised by the presence of organic matter, although this effect was less pronounced in seawater than in freshwater. Thus, in seawater of 6 to 33 ‰S, the removal of particles was fast (removal half time < 200 h), whereas the colloidal suspensions formed in freshwater were stable (removal half time > 900 h). Overall, oxidation of Fe(II) and removal of Fe(III) oxyhydroxide particles were much faster in seawater than in freshwater. This more rapid turnover results in lower iron availability in coastal seawater than in freshwater, making iron more likely to become a limiting element for chemical scavenging and biologic production.

A Radiofluorinated Divalent Cystine Knot Peptide for Tumor PET Imaging

DOE PAGES

Jiang, Lei; Kimura, Richard H.; Ma, Xiaowei; ...

2014-04-09

A divalent knottin containing two separate integrin binding epitopes (RGD) in the adjacent loops, 3-4A, was recently developed and reported in our previous publication. In the current study, 3-4A was radiofluorinated with a 4-nitrophenyl 2- 18F-fluoropropinate ( 18F-NFP) group and the resulting divalent positron emission tomography (PET) probe, 18F-FP–3-4A, was evaluated as a novel imaging probe to detect integrin αvβ3 positive tumors in living animals. Knottin 3-4A was synthesized by solid phase peptide synthesis, folded, and site-specifically conjugated with 18/19F-NFP to produce the fluorinated peptide 18/19F-fluoropropinate-3-4A ( 18/19F-FP–3-4A). The stability of 18F-FP–3-4A was tested in both phosphate buffered saline (PBS)more » buffer and mouse serum. Cell uptake assays of the radiolabeled peptides were performed using U87MG cells. In addition, small animal PET imaging and biodistribution studies of 18F-FP–3-4A were performed in U87MG tumor-bearing mice. The receptor targeting specificity of the radiolabeled peptide was also verified by coinjecting the probe with a blocking peptide cyclo(RGDyK). Our study showed that 18F-FP–3-4A exhibited excellent stability in PBS buffer (pH 7.4) and mouse serum. Small animal PET imaging and biodistribution data revealed that 18F-FP–3-4A exhibited rapid and good tumor uptake (3.76 ± 0.59% ID/g and 2.22 ± 0.62% ID/g at 0.5 and 1 h, respectively). 18F-FP–3-4A was rapidly cleared from the normal tissues, resulting in excellent tumor-to-normal tissue contrasts. For example, liver uptake was only 0.39 ± 0.07% ID/g and the tumor to liver ratio was 5.69 at 1 h p.i. Furthermore, coinjection of cyclo(RGDyK) with 18F-FP–3-4A significantly inhibited tumor uptake (0.41 ± 0.12 vs 1.02 ± 0.19% ID/g at 2.5 h) in U87MG xenograft models, demonstrating specific accumulation of the probe in the tumor. In summary, the divalent probe 18F-FP–3-4A is characterized by rapid and high tumor uptake and excellent tumor-to-normal tissue ratios. 18F-FP–3-4A is a highly promising knottin based PET probe for translating into clinical imaging of tumor angiogenesis.« less

Beneficial role of hydrophytes in removing Cr(VI) from wastewater in association with chromate-reducing bacterial strains Ochrobactrum intermedium and Brevibacterium.

PubMed

Faisal, Muhammad; Hasnain, Shahida

2005-01-01

This study deals with the use of three chromium-resistant bacterial strains (Ochrobactrum intermedium CrT-1, Brevibacterium CrT-13, and CrM-1) in conjunction with Eichornia crassipes for the removal of toxic chromium from wastewater. Bacterial strains resulted in reduced uptake of chromate into inoculated plants as compared to noninoculated control plants. In the presence of different heavy metals, chromium uptake into the plants was 28.7 and 7.15% less at an initial K2CrO4 concentration of 100 and 500 microg ml(-1) in comparison to a metal free chromium solution. K2CrO4 uptake into the plant occurred at different pHs tested, but maximum uptake was observed at pH 5. Nevertheless, the bacterial strains caused some decrease in chromate uptake into the plants, but the combined effect of plants and bacterial strains conduce more removal of Cr(VI) from the solution.

Engagement of men in antenatal care services: Increased HIV testing and treatment uptake in a community participatory action program in Mozambique

PubMed Central

Audet, Carolyn M.; Blevins, Meridith; Chire, Yazalde Manuel; Aliyu, Muktar H; Vaz, Lara M. E.; Antonio, Elisio; Alvim, Fernanda; Bechtel, Ruth; Wester, C. William; Vermund, Sten H.

2016-01-01

Uptake of HIV testing and antiretroviral therapy (ART) services during antenatal care (ANC) in rural Mozambique is disappointing. To nurture supportive male engagement in ANC services, we partnered with Traditional Birth Attendants and trained a new type of male-to-male community health agent, “Male Champions”, who focused on counseling male partners to create new, male-friendly community norms around engagement in spousal/partner pregnancies. We assessed ANC service uptake using a pre-post intervention design. The intervention was associated with increases in: (1) uptake of provider-initiated counseling and testing among pregnant woman (81% vs. 92%; p<0.001); (2) male engagement in ANC (5% vs. 34%; p<0.001); and (3) uptake of ART (8% vs. 19%; p<0.001). When men accepted HIV testing, rates of testing rose markedly among pregnant women. With the challenges in scale-up of Option B+ in sub-Saharan Africa, similar interventions may increase testing and treatment acceptability during pregnancy. PMID:26906021

Pharmacological characterization of a fluorescent uptake assay for the noradrenaline transporter.

PubMed

Haunsø, Anders; Buchanan, Dawn

2007-04-01

The noradrenaline transporter (NET) is a Na(+)/Cl(-) dependent monoamine transporter that mediates rapid clearance of noradrenaline from the synaptic cleft, thereby terminating neuronal signaling. NET is an important target for drug development and is known to be modulated by many psychoactive compounds, including psychostimulants and antidepressants. Here, the authors describe the development and pharmacological characterization of a nonhomogeneous fluorescent NET uptake assay using the compound 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP(+)). Data presented show that the pharmacology of both the classic radiolabeled (3)H-noradrenaline- and ASP(+)-based uptake assays are comparable, with an excellent correlation between potency obtained for known modulators of NET (r = 0.95, p < 0.0001). Furthermore, the fluorescent uptake assay is highly reproducible and has sufficiently large Z' values to be amenable for high-throughput screening (HTS). The advantage of this assay is compatibility with both 96- and 384-well formats and lack of radioactivity usage. Thus, the authors conclude that the assay is an inexpensive, viable approach for the identification and pharmacological profiling of small-molecule modulators of the monoamine transporter NET and may be amenable for HTS.

Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

PubMed

Baek, Jong-Suep; Cho, Cheong-Weon

2017-08-01

Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

PubMed Central

Misra, Madhusmita; Levitsky, Lynne L.

2015-01-01

Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

Diagnosis of pediatric hyperthyroidism: technetium 99 uptake versus thyroid stimulating immunoglobulins.

PubMed

Baskaran, Charumathi; Misra, Madhusmita; Levitsky, Lynne L

2015-01-01

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

A model analysis of arterial oxygen desaturation during apnea in preterm infants.

PubMed

Sands, Scott A; Edwards, Bradley A; Kelly, Vanessa J; Davidson, Malcolm R; Wilkinson, Malcolm H; Berger, Philip J

2009-12-01

Rapid arterial O(2) desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O(2) desaturation during apnea (Sa(O)₂) is complicated by the non-linear O(2) dissociation curve, falling pulmonary O(2) uptake, and by the fact that O(2) desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O(2) consumption accelerates Sa(O)₂throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar P(O)₂causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates Sa(O)₂during stage 1, and finally, total blood O(2) capacity (blood volume and hemoglobin content) alone determines Sa(O)₂during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia.

Interactions of Cadmium, Zinc, and Phosphorus in Marine Synechococcus: Field Uptake, Physiological and Proteomic Studies

DTIC Science & Technology

2011-06-01

numbers at harvest 170 Figure 4.6 Ratio of chlorophyll a to phycoerythrin fluorescence per cell 172 Figure 4.7 Cluster analysis of...performed at depths varying from 8-600 m. Bottles were incubated for 24 hours. Time course 110Cd uptake experiments involved bottles being harvested ...fold decrease in Synechococcus cell abundance in the control treatment at harvest compared to initial abundance, with an approximately two-fold

An epigenetic antimalarial resistance mechanism involving parasite genes linked to nutrient uptake.

PubMed

Sharma, Paresh; Wollenberg, Kurt; Sellers, Morgan; Zainabadi, Kayvan; Galinsky, Kevin; Moss, Eli; Nguitragool, Wang; Neafsey, Daniel; Desai, Sanjay A

2013-07-05

Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In Plasmodium falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag genes linked to channel activity, but had no genome-level changes. Silencing aborted production of the channel protein and was directly responsible for reduced uptake. Silencing affected clag paralogs on two chromosomes and was mediated by specific histone modifications, allowing a rapidly reversible drug resistance phenotype advantageous to the parasite. These findings implicate a novel epigenetic resistance mechanism that involves reduced host cell uptake and is a worrisome liability for water-soluble antimalarial drugs.

Phagocytosis: studies by optical tweezers and time-resolved microspectrofluorometry

NASA Astrophysics Data System (ADS)

Schneckenburger, Herbert; Sailer, Reinhard; Hendinger, Anita; Gschwend, Michael H.; Bauer, Manfred; Strauss, Wolfgang S. L.

1999-01-01

Cellular uptake of transparent Latex particles by J774A.1 mouse macrophages has been studied: First, single beads were kept within an optical light trap and located in close vicinity to individual cells. Uptake of the beads was visualized, and intrinsic fluorescence was detected in the spectral range of 420 - 530 nm. Second, time-gated fluorescence spectra of single cells were recorded at pre- selected times during one hour after cellular uptake. A rapid increase of autofluorescence and a subsequent decrease to the level of control cells within about 10 min. was measured within a time gate of 0 - 5 ns after the exciting laser pulses, and attributed to the 'free' coenzyme NAD(P)H. In contrast, fluorescence increase of NAD(P)H bound to proteins (measured within time gates of 5 - 10 ns or 10 - 15 ns) was less pronounced, and the subsequent decrease occurred within a longer period (about one hour).

WRKY6 Transcription Factor Restricts Arsenate Uptake and Transposon Activation in Arabidopsis[W

PubMed Central

Castrillo, Gabriel; Sánchez-Bermejo, Eduardo; de Lorenzo, Laura; Crevillén, Pedro; Fraile-Escanciano, Ana; TC, Mohan; Mouriz, Alfonso; Catarecha, Pablo; Sobrino-Plata, Juan; Olsson, Sanna; Leo del Puerto, Yolanda; Mateos, Isabel; Rojo, Enrique; Hernández, Luis E.; Jarillo, Jose A.; Piñeiro, Manuel; Paz-Ares, Javier; Leyva, Antonio

2013-01-01

Stress constantly challenges plant adaptation to the environment. Of all stress types, arsenic was a major threat during the early evolution of plants. The most prevalent chemical form of arsenic is arsenate, whose similarity to phosphate renders it easily incorporated into cells via the phosphate transporters. Here, we found that arsenate stress provokes a notable transposon burst in plants, in coordination with arsenate/phosphate transporter repression, which immediately restricts arsenate uptake. This repression was accompanied by delocalization of the phosphate transporter from the plasma membrane. When arsenate was removed, the system rapidly restored transcriptional expression and membrane localization of the transporter. We identify WRKY6 as an arsenate-responsive transcription factor that mediates arsenate/phosphate transporter gene expression and restricts arsenate-induced transposon activation. Plants therefore have a dual WRKY-dependent signaling mechanism that modulates arsenate uptake and transposon expression, providing a coordinated strategy for arsenate tolerance and transposon gene silencing. PMID:23922208

Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.

PubMed

Schaffert, David H; Okholm, Anders H; Sørensen, Rasmus S; Nielsen, Jesper S; Tørring, Thomas; Rosen, Christian B; Kodal, Anne Louise B; Mortensen, Michael R; Gothelf, Kurt V; Kjems, Jørgen

2016-05-01

DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fine-scale detection of pollutants by a benthic marine jellyfish.

PubMed

Epstein, Hannah E; Templeman, Michelle A; Kingsford, Michael J

2016-06-15

Local sources of pollution can vary immensely on small geographic scales and short time frames due to differences in runoff and adjacent land use. This study examined the rate of uptake and retention of trace metals in Cassiopea maremetens, a benthic marine jellyfish, over a short time frame and in the presence of multiple pollutants. This study also validated the ability of C. maremetens to uptake metals in the field. Experimental manipulation demonstrated that metal accumulation in jellyfish tissue began within 24h of exposure to treated water and trended for higher accumulation in the presence of multiple pollutants. C. maremetens was found to uptake trace metals in the field and provide unique signatures among locations. This fine-scale detection and rapid accumulation of metals in jellyfish tissue can have major implications for both biomonitoring and the trophic transfer of pollutants through local ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Opt-out provider-initiated HIV testing and counselling in primary care outpatient clinics in Zambia

PubMed Central

Chipukuma, Julien M; Chiko, Matimba M; Wamulume, Chibesa S; Bolton-Moore, Carolyn; Reid, Stewart E

2011-01-01

Abstract Objective To increase case-finding of infection with human immunodeficiency virus (HIV) in Zambia and their referral to HIV care and treatment by supplementing existing client-initiated voluntary counselling and testing (VCT), the dominant mode of HIV testing in the country. Methods Lay counsellors offered provider-initiated HIV testing and counselling (PITC) to all outpatients who attended primary clinics and did not know their HIV serostatus. Data on counselling and testing were collected in registers. Outcomes of interest included HIV testing coverage, the acceptability of testing, the proportion testing HIV-positive (HIV+), the proportion enrolling in HIV care and treatment and the time between testing and enrolment. Findings After the addition of PITC to VCT, the number tested for HIV infection in the nine clinics was twice the number undergoing VCT alone. Over 30 months, 44 420 patients were counselled under PITC and 31 197 patients, 44% of them men, accepted testing. Of those tested, 21% (6572) were HIV+; 38% of these HIV+ patients (2515) enrolled in HIV care and treatment. The median time between testing and enrolment was 6 days. The acceptability of testing rose over time. Conclusion The introduction of routine PITC using lay counsellors into health-care clinics in Lusaka, Zambia, dramatically increased the uptake and acceptability of HIV testing. Moreover, PITC was incorporated rapidly into primary care outpatient departments. Maximizing the number of patients who proceed to HIV care and treatment remains a challenge and warrants further research. PMID:21556300

Perceived Utility of the RE-AIM Framework for Health Promotion/Disease Prevention Initiatives for Older Adults: A Case Study from the U.S. Evidence-Based Disease Prevention Initiative.

PubMed

Ory, Marcia G; Altpeter, Mary; Belza, Basia; Helduser, Janet; Zhang, Chen; Smith, Matthew Lee

2014-01-01

Dissemination and implementation (D&I) frameworks are increasingly being promoted in public health research. However, less is known about their uptake in the field, especially for diverse sets of programs. Limited questionnaires exist to assess the ways that frameworks can be utilized in program planning and evaluation. We present a case study from the United States that describes the implementation of the RE-AIM framework by state aging services providers and public health partners and a questionnaire that can be used to assess the utility of such frameworks in practice. An online questionnaire was developed to capture community perspectives about the utility of the RE-AIM framework. Distributed to project leads in 27 funded states in an evidence-based disease prevention initiative for older adults, 40 key stakeholders responded representing a 100% state-participation rate among the 27 funded states. Findings suggest that there is perceived utility in using the RE-AIM framework when evaluating grand-scale initiatives for older adults. The RE-AIM framework was seen as useful for planning, implementation, and evaluation with relevance for evaluators, providers, community leaders, and policy makers. Yet, the uptake was not universal, and some respondents reported difficulties in use, especially adopting the framework as a whole. This questionnaire can serve as the basis to assess ways the RE-AIM framework can be utilized by practitioners in state-wide D&I efforts. Maximal benefit can be derived from examining the assessment of RE-AIM-related knowledge and confidence as part of a continual quality assurance process. We recommend such an assessment be performed before the implementation of new funding initiatives and throughout their course to assess RE-AIM uptake and to identify areas for technical assistance.

Radiolabeling and initial biological evaluation of [18F]KBM-1 for imaging RAR-α receptors in neuroblastoma.

PubMed

Solingapuram Sai, Kiran Kumar; Das, Bhaskar C; Sattiraju, Anirudh; Almaguel, Frankis G; Craft, Suzanne; Mintz, Akiva

2017-03-15

Retinoic acid receptor alpha (RAR-α) plays a significant role in a number of diseases, including neuroblastoma. Children diagnosed with high-risk neuroblastoma are treated13-cis-retinoic acid, which reduces risk of cancer recurrence. Neuroblastoma cell death is mediated via RAR-α, and expression of RAR-α is upregulated after treatment. A molecular imaging probe that binds RAR-α will help clinicians to diagnose and stratify risk for patients with neuroblastoma, who could benefit from retinoid-based therapy. In this study, we report the radiolabeling, and initial in vivo evaluation of [ 18 F]KBM-1, a novel RAR-α agonist. The radiochemical synthesis of [ 18 F]KBM-1 was carried out through KHF 2 assisted substitution of [ 18 F] - from aryl-substituted pinacolatoesters-based retinoid precursor. In vitro cell uptake assay in human neuroblastoma cell line showed that the uptake of [ 18 F]KBM-1 was significantly inhibited by all three blocking agents (KBM-1, ATRA, BD4) at all the selected incubation times. Standard biodistribution in mice bearing neuroblastoma tumors demonstrated increased tumor uptake from 5min to 60min post radiotracer injection and the uptake ratios for target to non-target (tumor: muscle) increased 2.2-fold to 3.7-fold from 30min to 60min post injection. Tumor uptake in subset of 30min blocking group was 1.7-fold lower than unblocked. These results demonstrate the potential utility of [ 18 F]KBM-1 as a RAR-α imaging agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel fluorescent assay for sucrose transporters.

PubMed

Gora, Peter J; Reinders, Anke; Ward, John M

2012-04-04

We have developed a novel assay based on the ability of type I sucrose uptake transporters (SUTs) to transport the fluorescent coumarin β-glucoside, esculin. Budding yeast (Saccharomyces cerevisiae) is routinely used for the heterologous expression of SUTs and does not take up esculin. When type I sucrose transporters StSUT1 from potato or AtSUC2 from Arabidopsis were expressed in yeast, the cells were able to take up esculin and became brightly fluorescent. We tested a variety of incubation times, esculin concentrations, and buffer pH values and found that for these transporters, a 1 hr incubation at 0.1 to 1 mM esculin at pH 4.0 produced fluorescent cells that were easily distinguished from vector controls. Esculin uptake was assayed by several methods including fluorescence microscopy, spectrofluorometry and fluorescence-activiated cell sorting (FACS). Expression of the type II sucrose transporter OsSUT1 from rice did not result in increased esculin uptake under any conditions tested. Results were reproduced successfully in two distinct yeast strains, SEY6210 (an invertase mutant) and BY4742. The esculin uptake assay is rapid and sensitive and should be generally useful for preliminary tests of sucrose transporter function by heterologous expression in yeast. This assay is also suitable for selection of yeast showing esculin uptake activity using FACS.

Phosphate uptake studies of cross-linked chitosan bead materials.

PubMed

Mahaninia, Mohammad H; Wilson, Lee D

2017-01-01

A systematic experimental study is reported that provides a molecular based understanding of cross-linked chitosan beads and their adsorption properties in aqueous solution containing phosphate dianion (HPO 4 2- ) species. Synthetically modified chitosan using epichlorohydrin and glutaraldehyde cross-linkers result in surface modified beads with variable hydrophile-lipophile character and tunable HPO 4 2- uptake properties. The kinetic and thermodynamic adsorption properties of cross-linked chitosan beads with HPO 4 2- species were studied in aqueous solution. Complementary structure and physicochemical characterization of chitosan beads via potentiometry, Raman spectroscopy, DSC, and dye adsorption measurements was carried out to establish structure-property relationships. The maximum uptake (Q m ) of bead systems with HPO 4 2- at equilibrium was 52.1mgg -1 ; whereas, kinetic uptake results for chitosan bead/phosphate systems are relatively rapid (0.111-0.113min -1 ) with an intraparticle diffusion rate-limiting step. The adsorption process follows a multi-step pathway involving inner- and outer-sphere complexes with significant changes in hydration. Phosphate uptake strongly depends on the composition and type of cross-linker used for preparation of chitosan beads. The adsorption isotherms and structural characterization of bead systems illustrate the role of surface charge, hydrophile-lipophile balance, adsorption site accessibility, and hydration properties of the chitosan bead surface. Copyright © 2016 Elsevier Inc. All rights reserved.

Predicting dietborne metal toxicity from metal influxes

USGS Publications Warehouse

Croteau, M.-N.; Luoma, S.N.

2009-01-01

Dietborne metal uptake prevails for many species in nature. However, the links between dietary metal exposure and toxicity are not well understood. Sources of uncertainty include the lack of suitable tracers to quantify exposure for metals such as copper, the difficulty to assess dietary processes such as food ingestion rate, and the complexity to link metal bioaccumulation and effects. We characterized dietborne copper, nickel, and cadmium influxes in a freshwater gastropod exposed to diatoms labeled with enriched stable metal isotopes. Metal influxes in Lymnaea stagnalis correlated linearly with dietborne metal concentrations over a range encompassing most environmental exposures. Dietary Cd and Ni uptake rate constants (kuf) were, respectively, 3.3 and 2.3 times higher than that for Cu. Detoxification rate constants (k detox) were similar among metals and appeared 100 times higher than efflux rate constants (ke). Extremely high Cu concentrations reduced feeding rates, causing the relationship between exposure and influx to deviate from linearity; i.e., Cu uptake rates leveled off between 1500 and 1800 nmol g-1 day-1. L. stagnalis rapidly takes up Cu, Cd, and Ni from food but detoxifies the accumulated metals, instead of reducing uptake or intensifying excretion. Above a threshold uptake rate, however, the detoxification capabilities of L. stagnalis are overwhelmed.

Stimulation of Cl- uptake and morphological changes in gill mitochondria-rich cells in freshwater tilapia (Oreochromis mossambicus).

PubMed

Chang, Il-Chi; Wei, Yuan-Yaw; Chou, Fong-In; Hwang, Pung-Pung

2003-01-01

The purpose of the present article is to examine the relationships between ion uptakes and morphologies of gill mitochondria-rich (MR) cells in freshwater tilapia. Tilapia were acclimated to three different artificial freshwaters (high Na [10 mM], high Cl [7.5 mM]; high Na, low Cl [0.02-0.07 mM], and low Na [0.5 mM], low Cl) for 1 wk, and then morphological measurements of gill MR cells were made and ion influxes were determined. The number and the apical size of wavy-convex MR cells positively associated with the level of Cl(-) influx. Conversely, Na(+) influx showed no positive correlation with the morphologies of MR cells. The dominant MR cell type in tilapia gills changed from deep-hole to wavy-convex within 6 h after acute transfer from a high-Cl(-) to a low-Cl(-) environment. Deep-hole MR cells became dominant 24-96 h after acute transfer from a low-Cl(-) to a high-Cl(-) environment. We conclude that wavy-convex MR cells associate with Cl(-) uptake but not Na(+) uptake, and the rapid formation of wavy-convex MR cells reflects the timely stimulation of Cl(-) uptake to recover the homeostasis of internal Cl(-) levels on acute challenge with low environmental Cl(-).

Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited.

PubMed

Vazquez, Alexei; Liu, Jiangxia; Zhou, Yi; Oltvai, Zoltán N

2010-05-06

Cancer cells simultaneously exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen, a phenomenon known as the Warburg effect. The maintenance of this mixed metabolic phenotype is seemingly counterintuitive given that aerobic glycolysis is far less efficient in terms of ATP yield per moles of glucose than mitochondrial respiration. Here, we resolve this apparent contradiction by expanding the notion of metabolic efficiency. We study a reduced flux balance model of ATP production that is constrained by the glucose uptake capacity and by the solvent capacity of the cell's cytoplasm, the latter quantifying the maximum amount of macromolecules that can occupy the intracellular space. At low glucose uptake rates we find that mitochondrial respiration is indeed the most efficient pathway for ATP generation. Above a threshold glucose uptake rate, however, a gradual activation of aerobic glycolysis and slight decrease of mitochondrial respiration results in the highest rate of ATP production. Our analyses indicate that the Warburg effect is a favorable catabolic state for all rapidly proliferating mammalian cells with high glucose uptake capacity. It arises because while aerobic glycolysis is less efficient than mitochondrial respiration in terms of ATP yield per glucose uptake, it is more efficient in terms of the required solvent capacity. These results may have direct relevance to chemotherapeutic strategies attempting to target cancer metabolism.

Selective binding and transcytosis of Ulex europaeus 1 lectin by mouse Peyer's patch M-cells in vivo.

PubMed

Clark, M A; Jepson, M A; Simmons, N L; Hirst, B H

1995-12-01

The in vivo interaction of the lectin Ulex europaeus agglutinin 1 with mouse Peyer's patch follicle-associated epithelial cells was studied in the mouse Peyer's patch gut loop model by immunofluorescence and electron microscopy. The lectin targets to mouse Peyer's patch M-cells and is rapidly endocytosed and transcytosed. These processes are accompanied by morphological changes in the M-cell microvilli and by redistribution of polymerised actin. The demonstration of selective binding and uptake of a lectin by intestinal M-cells in vivo suggests that M-cell-specific surface glycoconjugates might act as receptors for the selective adhesion/uptake of microorganisms.

Nitric oxide generated by nitrate reductase increases nitrogen uptake capacity by inducing lateral root formation and inorganic nitrogen uptake under partial nitrate nutrition in rice

PubMed Central

Sun, Huwei; Li, Jiao; Song, Wenjing; Tao, Jinyuan; Huang, Shuangjie; Chen, Si; Hou, Mengmeng; Xu, Guohua; Zhang, Yali

2015-01-01

Increasing evidence shows that partial nitrate nutrition (PNN) can be attributed to improved plant growth and nitrogen-use efficiency (NUE) in rice. Nitric oxide (NO) is a signalling molecule involved in many physiological processes during plant development and nitrogen (N) assimilation. It remains unclear whether molecular NO improves NUE through PNN. Two rice cultivars (cvs Nanguang and Elio), with high and low NUE, respectively, were used in the analysis of NO production, nitrate reductase (NR) activity, lateral root (LR) density, and 15N uptake under PNN, with or without NO production donor and inhibitors. PNN increased NO accumulation in cv. Nanguang possibly through the NIA2-dependent NR pathway. PNN-mediated NO increases contributed to LR initiation, 15NH4 +/15NO3 – influx into the root, and levels of ammonium and nitrate transporters in cv. Nanguang but not cv. Elio. Further results revealed marked and specific induction of LR initiation and 15NH4 +/15NO3 – influx into the roots of plants supplied with NH4 ++sodium nitroprusside (SNP) relative to those supplied with NH4 + alone, and considerable inhibition upon the application of cPTIO or tungstate (NR inhibitor) in addition to PNN, which is in agreement with the change in NO fluorescence in the two rice cultivars. The findings suggest that NO generated by the NR pathway plays a pivotal role in improving the N acquisition capacity by increasing LR initiation and the inorganic N uptake rate, which may represent a strategy for rice plants to adapt to a fluctuating nitrate supply and increase NUE. PMID:25784715

Calmodulin antagonists have differential effects on Ca/sup 2 +/ uptake, (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase and Ca/sup 2 +/ release in hepatic endoplasmic reticulum

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

Delfert, D.M.; Koepnick, S.; McDonald, J.M.

1986-05-01

The effect of calmodulin (CaM) antagonists on Ca/sup 2 +/ handling by hepatic endoplasmic reticulum (ER) was studied. Ca/sup 2 +/ uptake by saponin-permeabilized hepatocytes or isolated ER was measured using /sup 45/Ca/sup 2 +/ in a filtration assay in the presence of 0.09 ..mu..M free (Ca/sup 2 +/) and inhibitors of mitochondrial Ca/sup 2 +/ transport. Each CaM-antagonist (chlorpromazine, CPZ; trifluoperazine, TFP; calmidazolium, W7 and 48/80) showed a dose-dependent inhibition of Ca/sup 2 +/ accumulation in permeabilized hepatocytes. Both the initial rate and steady state values for Ca/sup 2 +/ uptake were reduced by 50% with 40 ..mu..M calmidazolium,more » 100 ..mu..M TFP, 150..mu..M W7, 150 ..mu..M CPZ and 300 ..mu..M 48/80. Using isolated ER both calmidazolium (20 ..mu..M) and W7 (150 ..mu..M) inhibited the initial rate and steady state level of Ca/sup 2 +/ accumulation. At this concentration calmidazolium inhibited the initial rate of (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase activity, and enhanced Ca/sup 2 +/ release. In contrast, W7 had no effect on these parameters. These results suggest that the reduced level of Ca/sup 2 +/ uptake into ER vesicles in the presence of calmidazolium may result from inhibition of the (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase as well as induction of Ca/sup 2 +/ release, while W7 may act to uncouple Ca/sup 2 +/ transport from its (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase counterpart.« less

Use of an Innovative Personality-Mindset Profiling Tool to Guide Culture-Change Strategies among Different Healthcare Worker Groups.

PubMed

Grayson, M Lindsay; Macesic, Nenad; Huang, G Khai; Bond, Katherine; Fletcher, Jason; Gilbert, Gwendolyn L; Gordon, David L; Hellsten, Jane F; Iredell, Jonathan; Keighley, Caitlin; Stuart, Rhonda L; Xuereb, Charles S; Cruickshank, Marilyn

2015-01-01

Important culture-change initiatives (e.g. improving hand hygiene compliance) are frequently associated with variable uptake among different healthcare worker (HCW) categories. Inherent personality differences between these groups may explain change uptake and help improve future intervention design. We used an innovative personality-profiling tool (ColourGrid®) to assess personality differences among standard HCW categories at five large Australian hospitals using two data sources (HCW participant surveys [PS] and generic institution-wide human resource [HR] data) to: a) compare the relative accuracy of these two sources; b) identify differences between HCW groups and c) use the observed profiles to guide design strategies to improve uptake of three clinically-important initiatives (improved hand hygiene, antimicrobial stewardship and isolation procedure adherence). Results from 34,243 HCWs (HR data) and 1045 survey participants (PS data) suggest that HCWs were different from the general population, displaying more individualism, lower power distance, less uncertainty avoidance and greater cynicism about advertising messages. HR and PS data were highly concordant in identifying differences between the three key HCW categories (doctors, nursing/allied-health, support services) and predicting appropriate implementation strategies. Among doctors, the data suggest that key messaging should differ between full-time vs part-time (visiting) senior medical officers (SMO, VMO) and junior hospital medical officers (HMO), with SMO messaging focused on evidence-based compliance, VMO initiatives emphasising structured mandatory controls and prestige loss for non-adherence, and for HMOs focusing on leadership opportunity and future career risk for non-adherence. Compared to current standardised approaches, targeted interventions based on personality differences between HCW categories should result in improved infection control-related culture-change uptake. Personality profiling based on HR data may represent a useful means of developing a national culture-change "blueprint" for HCW education.

Water flow and solute transport in the soil-plant-atmosphere continuum: Upscaling from rhizosphere to root zone

NASA Astrophysics Data System (ADS)

Lazarovitch, Naftali; Perelman, Adi; Guerra, Helena; Vanderborght, Jan; Pohlmeier, Andreas

2016-04-01

Root water and nutrient uptake are among the most important processes considered in numerical models simulating water content and fluxes in the subsurface, as they control plant growth and production as well as water flow and nutrient transport out of the root zone. Root water uptake may lead to salt accumulation at the root-soil interface, resulting in rhizophere salt concentrations much higher than in the bulk soil. This salt accumulation is caused by soluble salt transport towards the roots by mass flow through the soil, followed by preferential adsorption of specific nutrients by active uptake, thereby excluding most other salts at the root-soil interface or in the root apoplast. The salinity buildup can lead to large osmotic pressure gradients across the roots thereby effectively reducing root water uptake. The initial results from rhizoslides (capillary paper growth system) show that sodium concentration is decreasing with distance from the root, compared with the bulk that remained more stable. When transpiration rate was decreased under high salinity levels, sodium concentration was more homogenous compared with low salinity levels. Additionally, sodium and gadolinium distributions were measured nondestructively around tomato roots using magnetic resonance imaging (MRI). This technique could also observe the root structure and water content around single roots. Results from the MRI confirm the solutes concentration pattern around roots and its relation to their initial concentration. We conclude that local water potentials at the soil-root interface differ from bulk potentials. These relative differences increase with decreasing root density, decreasing initial salt concentration and increasing transpiration rate. Furthermore, since climate may significantly influence plant response to salinity a dynamic climate-coupled salinity reduction functions are critical in while using macroscopic numerical models.

Human papillomavirus vaccine uptake among 18- to 26-year-old women in the United States: National Health Interview Survey, 2010.

PubMed

Laz, Tabassum H; Rahman, Mahbubur; Berenson, Abbey B

2013-04-01

Human papillomavirus (HPV) vaccine uptake among young adult women has been reported to be very low. The authors conducted this study to provide an update on HPV vaccine uptake among 18- to 26-year-old women. The authors used the National Health Interview Survey 2010 data to estimate HPV vaccine coverage and their correlates. Overall, 22.7% of women initiated (≥1 dose) and 12.7% completed the vaccine (≥3 doses). Thus, about 56% of women who initiated the vaccine completed it. Multivariate logistic regression analyses showed that younger age, unmarried status, Papanicolaou test, influenza vaccine, lifetime vaccines, and HPV vaccine awareness were positively associated with receiving ≥1 and ≥3 doses. In addition, uninsured women were less likely to receive ≥1 dose (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28-0.84), and blacks (OR, 0.48; 95% CI, 0.23-0.99) and women with a family income <100% of the federal poverty level (OR, 0.40; 95% CI, 0.21-0.73) were less likely to receive ≥3 doses. Furthermore, based on vaccine initiators, blacks were less likely than whites to complete the vaccine (OR, 0.29; 95% CI, 0.16-0.55). Two thirds of unvaccinated women were not interested in future vaccination. Among those who were interested, >76.4% preferred to receive it free or at a lower cost, whereas 20% would pay the full cost of the vaccine. One in 8 women completed the 3-dose HPV vaccine. Educational and vaccine financing programs are needed to improve the uptake among low-income minority women who are at increased risk for cervical cancer. Copyright © 2012 American Cancer Society.

Regulation of the Na+2Cl–K+ cotransporter in in vitro perfused rectal gland tubules of Squalus acanthias.

PubMed

Warth, R; Bleich, M; Thiele, I; Lang, F; Greger, R

1998-07-01

Previously it has been shown that the Na+2Cl–K+ cotransporter accepts NH4 + at its K+ binding site. This property can be used to estimate its transport rates by adding NH4 + to the bath and measuring the initial furosemide-dependent rates of change in BCECF fluorescence. We have utilized this technique to determine the regulation of the furosemide-inhibitable Na+2Cl–K+ cotransporter in in vitroperfused rectal gland tubules (RGT) of Squalus acanthias. Addition of NH4 + to the bath (20 mmol/l) led to an initial alkalinization, corresponding to NH3 uptake. This was followed by an acidification, corresponding to NH4 + uptake. The rate of this uptake was quantified by exponential curve fitting and is given in arbitrary units (Δfluorescence/time). This acidification could be completely inhibited by furosemide. In the absence of any secretagogue preincubation of RGT in a low Cl– solution (6 mmol/l, low Cl–) for 10 min enhanced the uptake rate significantly from 4.04±0.51 to 12.7±1.30 (n=5). The addition of urea (200 mmol/l) was without effect, but the addition of 300 mmol/l mannitol (+300 mannitol) enhanced the rate significantly from 7.24±1.33 to 14.7±4.6 (n=6). Stimulation of NaCl secretion by a solution maximizing the cytosolic cAMP concentration (Stim) led to a significant increase in NH4 + uptake rate from 5.00±1.33 to 13.3±1.54 (n=6). Similar results were obtained in the additional presence of Ba2+ (1 mmol/l): the uptake rate was increased significantly from 4.23±0.34 to 15.1±1.86 (n=16). In the presence of Stim low Cl– had no additional effect on the uptake rate: 15.1±3.1 versus 15.2±2.8 in high Cl– (n=6). The uptake rate in Stim containing additional +300 mannitol (22.3±4.0, n=5) was not significantly different from that obtained with Stim or +300 mannitol alone. By whatever mechanism the NH4 + uptake rate was increased furosemide (500 µmol/l) always reduced this rate to control values. Hence three manoeuvres enhanced furosemide-inhibitable uptake rates of the Na+2Cl–K+ cotransporter probably independently: (1) lowering of cytosolic Cl– concentration; (2) cell shrinkage; and (3) activation by cAMP.

Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure.

PubMed

Nedredal, Geir I; Elvevold, Kjetil; Chedid, Marcio F; Ytrebø, Lars M; Rose, Christopher F; Sen, Sambit; Smedsrød, Bård; Jalan, Rajiv; Revhaug, Arthur

2016-01-01

Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. As compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease.

Impact of a Pharmacy Benefit Change on New Use of Mail Order Pharmacy among Diabetes Patients: The Diabetes Study of Northern California (DISTANCE)

PubMed Central

Karter, Andrew J; Parker, Melissa M; Duru, O Kenrik; Schillinger, Dean; Adler, Nancy E; Moffet, Howard H; Adams, Alyce S; Chan, James; Herman, Willam H; Schmittdiel, Julie A

2015-01-01

Objective To assess the impact of a pharmacy benefit change on mail order pharmacy (MOP) uptake. Data Sources/Study Setting Race-stratified, random sample of diabetes patients in an integrated health care delivery system. Study Design In this natural experiment, we studied the impact of a pharmacy benefit change that conditionally discounted medications if patients used MOP and prepaid two copayments. We compared MOP uptake among those exposed to the benefit change (n = 2,442) and the reference group with no benefit change (n = 8,148), and estimated differential MOP uptake across social strata using a difference-in-differences framework. Data Collection/Extraction Methods Ascertained MOP uptake (initiation among previous nonusers). Principal Findings Thirty percent of patients started using MOP after receiving the benefit change versus 9 percent uptake among the reference group (p < .0001). After adjustment, there was a 26 percentage point greater MOP uptake (benefit change effect). This benefit change effect was significantly smaller among patients with inadequate health literacy (15 percent less), limited English proficiency (14 percent less), and among Latinos and Asians (24 and 16 percent less compared to Caucasians). Conclusions Conditionally discounting medications delivered by MOP effectively stimulated MOP uptake overall, but it unintentionally widened previously existing social gaps in MOP use because it stimulated less MOP uptake in vulnerable populations. PMID:25131156

EFFECTS OF FERTILIZER ADDITION ON MICROBIAL RESPIRATION AND UPTAKE OF CARBON MONOXIDE IN A CERRADO SOIL

EPA Science Inventory

The savanna area in central Brazil (Cerrado) is undergoing rapid agricultural land use changes and these changes are often accompanied by fertilization of the land. Because fertilization is a widespread management practice in the Cerrado, it is important to understand the effect...

Beauveria bassiana, Metarhizium anisopliae, and Metarhizium anisopliae var. acridum conidia: tolerance to imbibitional damage

USDA-ARS?s Scientific Manuscript database

When dry fungal cells are immersed in water, rapid imbibition (water uptake) may compromise the plasma membrane, killing the cell. This study investigated the impact of imbibitional damage (measured in terms of reduced viability) on Beauveria bassiana (Bb), Metarhizium anisopliae (Ma) and M. anisop...

Fertilization [Chapter 11

Treesearch

Douglass F. Jacobs; Thomas D. Landis

2009-01-01

Fertilization is one of the most critical components of producing high-quality nursery stock. Seedlings rapidly deplete mineral nutrients stored within seeds, and cuttings have limited nutrient reserves. Therefore, to achieve desired growth rates, nursery plants must rely on root uptake of nutrients from the growing medium. Plants require adequate quantities of mineral...

Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

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

Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai

Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood.more » Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.« less

Blood and exhaled air can be used for biomonitoring of hydrofluorocarbon exposure.

PubMed

Ernstgård, Lena; Sjögren, Bengt; Gunnare, Sara; Johanson, Gunnar

2014-02-10

Various hydrofluorocarbons (HFCs) have replaced the ozone-depleting chlorofluorocarbons and hydrochlorofluorocarbons during the last decades. The objective of this study was to examine the usefulness of blood and breath for exposure biomonitoring of HFCs. We compared data on blood and exhaled air from a series of experiments where healthy volunteers were exposed to vapors of four commonly used HFCs; 1,1-difluoroethane, 1,1,1-trifluoroethane, 1,1,1,2-tetrafluoroethane, and 1,1,1,3,3-pentafluoropropane. All four HFCs had similar toxicokinetic profiles in blood with a rapid initial increase and an apparent steady-state reached within a few minutes. For all HFCs, the inhalation uptake during exposure was low (less than 6%), most of which was exhaled post-exposure. No metabolism could be detected and only minor amounts were excreted unchanged in urine. The observed time courses in blood and breath were well described by physiologically-based pharmacokinetic (PBPK) modeling. Simulations of 8-h exposures show that the HFC levels in both blood and breath drop rapidly during the first minutes post-exposure, whereafter the decline is considerably slower and mainly reflects washout from fat tissues. We conclude that blood and exhaled air can be used for biological exposure monitoring. Samples should not be taken immediately at the end of shift but rather 20-30 min later. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro

PubMed Central

Yang, Sheng-Huei; Tsai, Po-Wei; Wang, Shwu-Huey; Wang, Ching-Chiung; Lee, Yee-Shin; Cheng, Guei-Yun; HuangFu, Wei-Chun; London, David; Tang, Heng-Yuan; Fu, Earl; Yen, Yun; Liu, Leroy F.; Lin, Hung-Yun; Davis, Paul J.

2014-01-01

We have used a perfusion bellows cell culture system to investigate resveratrolinduced anti-proliferation/apoptosis in a human estrogen receptor (ER)-negative breast cancer cell line (MDA-MB-231). Using an injection system to perfuse media with stilbene, we showed resveratrol (0.5 – 100 μM) to decrease cell proliferation in a concentration-dependent manner. Comparison of influx and medium efflux resveratrol concentrations revealed rapid disappearance of the stilbene, consistent with cell uptake and metabolism of the agent reported by others. Exposure of cells to 10 μM resveratrol for 4 h daily × 6 d inhibited cell proliferation by more than 60%. Variable extracellular acid-alkaline conditions (pH 6.8 – 8.6) affected basal cell proliferation rate, but did not alter anti-proliferation induced by resveratrol. Resveratrol-induced gene expression, including transcription of the most up-regulated genes and pro-apoptotic p53-dependent genes, was not affected by culture pH changes. The microarray findings in the context of induction of anti-proliferation with brief daily exposure of cells to resveratrol—and rapid disappearance of the compound in the perfusion system—are consistent with existence of an accessible initiation site for resveratrol actions on tumor cells, e.g., the cell surface receptor for resveratrol described on integrin αvβ3. PMID:25436977

40 CFR Appendix B to Part 132 - Great Lakes Water Quality Initiative

Code of Federal Regulations, 2011 CFR

2011-07-01

... WATER QUALITY GUIDANCE FOR THE GREAT LAKES SYSTEM Pt. 132, App. B Appendix B to Part 132—Great Lakes Water Quality Initiative Methodology for Deriving Bioaccumulation Factors Great Lakes States and Tribes... system. For log KOW, the log of the octanol-water partition coefficient is a base 10 logarithm. Uptake...

40 CFR Appendix B to Part 132 - Great Lakes Water Quality Initiative

Code of Federal Regulations, 2010 CFR

2010-07-01

... WATER QUALITY GUIDANCE FOR THE GREAT LAKES SYSTEM Pt. 132, App. B Appendix B to Part 132—Great Lakes Water Quality Initiative Methodology for Deriving Bioaccumulation Factors Great Lakes States and Tribes... system. For log KOW, the log of the octanol-water partition coefficient is a base 10 logarithm. Uptake...

Mechanisms for the increase in phosphorus uptake of waterlogged plants: soil phosphorus availability, root morphology and uptake kinetics.

PubMed

Rubio, Gerardo; Oesterheld, Martín; Alvarez, Carina R; Lavado, Raúl S

1997-10-01

Waterlogging frequently reduces plant biomass allocation to roots. This response may result in a variety of alterations in mineral nutrition, which range from a proportional lowering of whole-plant nutrient concentration as a result of unchanged uptake per unit of root biomass, to a maintenance of nutrient concentration by means of an increase in uptake per unit of root biomass. The first objective of this paper was to test these two alternative hypothetical responses. In a pot experiment, we evaluated how plant P concentration of Paspalum dilatatum, (a waterlogging-tolerant grass from the Flooding Pampa, Argentina) was affected by waterlogging and P supply and how this related to changes in root-shoot ratio. Under both soil P levels waterlogging reduced root-shoot ratios, but did not reduce P concentration. Thus, uptake of P per unit of root biomass increased under waterlogging. Our second objective was to test three non-exclusive hypotheses about potential mechanisms for this increase in P uptake. We hypothesized that the greater P uptake per unit of root biomass was a consequence of: (1) an increase in soil P availability induced by waterlogging; (2) a change in root morphology, and/or (3) an increase in the intrinsic uptake capacity of each unit of root biomass. To test these hypotheses we evaluated (1) changes in P availability induced by waterlogging; (2) specific root length of waterlogged and control plants, and (3) P uptake kinetics in excised roots from waterlogged and control plants. The results supported the three hypotheses. Soil P avail-ability was higher during waterlogging periods, roots of waterlogged plants showed a morphology more favorable to nutrient uptake (finer roots) and these roots showed a higher physiological capacity to absorb P. The results suggest that both soil and plant mechanisms contributed to compensate, in terms of P nutrition, for the reduction in allocation to root growth. The rapid transformation of the P uptake system is likely an advantage for plants inhabiting frequently flooded environments with low P fertility, like the Flooding Pampa. This advantage would be one of the reasons for the increased relative abundance of P. dilatatum in the community after waterlogging periods.

Heterogeneous uptake of ammonia and dimethylamine into sulfuric and oxalic acid particles

NASA Astrophysics Data System (ADS)

Sauerwein, Meike; Keung Chan, Chak

2017-05-01

Heterogeneous uptake is one of the major mechanisms governing the amounts of short-chain alkylamines and ammonia (NH3) in atmospheric particles. Molar ratios of aminium to ammonium ions detected in ambient aerosols often exceed typical gas phase ratios. The present study investigated the simultaneous uptake of dimethylamine (DMA) and NH3 into sulfuric and oxalic acid particles at gaseous DMA / NH3 molar ratios of 0.1 and 0.5 at 10, 50 and 70 % relative humidity (RH). Single-gas uptake and co-uptake were conducted under identical conditions and compared. Results show that the particulate dimethyl-aminium/ammonium molar ratios (DMAH / NH4) changed substantially during the uptake process, which was severely influenced by the extent of neutralisation and the particle phase state. In general, DMA uptake and NH3 uptake into concentrated H2SO4 droplets were initially similarly efficient, yielding DMAH / NH4 ratios that were similar to DMA / NH3 ratios. As the co-uptake continued, the DMAH / NH4 gradually dropped due to a preferential uptake of NH3 into partially neutralised acidic droplets. At 50 % RH, once the sulfate droplets were neutralised, the stronger base DMA displaced some of the ammonium absorbed earlier, leading to DMAH / NH4 ratios up to four times higher than the corresponding gas phase ratios. However, at 10 % RH, crystallisation of partially neutralised sulfate particles prevented further DMA uptake, while NH3 uptake continued and displaced DMAH+, forming almost pure ammonium sulfate. Displacement of DMAH+ by NH3 has also been observed in neutralised, solid oxalate particles. The results can explain why DMAH / NH4 ratios in ambient liquid aerosols can be larger than DMA / NH3, despite an excess of NH3 in the gas phase. An uptake of DMA to aerosols consisting of crystalline ammonium salts, however, is unlikely, even at comparable DMA and NH3 gas phase concentrations.

Effects of Tityus serrulatus scorpion venom and its toxin TsTX-V on neurotransmitter uptake in vitro

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

Cecchini, Alessandra L.; Vollum Institute, Oregon Health Sciences University, Portland, Oregon 9701; Vasconcelos, Flavio

2006-12-01

Scorpion neurotoxins targeting the Na{sub v} channel can be classified into two classes: {alpha}- and {beta}-neurotoxins and are reported as highly active in mammalian brain. In this work, we evaluate the effects of Tityus serrulatus venom (Ts venom) and its {alpha}-neurotoxin TsTX-V on {gamma}-aminobutyric acid (GABA), dopamine (DA) and glutamate (Glu) uptake in isolated rat brain synaptosomes. TsTX-V was isolated from Ts venom by ion exchange chromatography followed by reverse-phase (C18) high-performance liquid chromatography. Neither Ts venom nor TsTX-V was able to affect {sup 3}H-Glu uptake. On the other hand, Ts venom (0.13 {mu}g/mg) significantly inhibited both {sup 3}H-GABA andmore » {sup 3}H-DA uptake ({approx} 50%). TsTX-V showed IC{sub 5} values of 9.37 {mu}M and 22.2 {mu}M for the inhibition of {sup 3}H-GABA and {sup 3}H-DA uptake, respectively. These effects were abolished by pre-treatment with tetrodotoxin (TTX, 1 {mu}M), indicating the involvement of voltage-gated Na{sup +} channels in this process. In the absence of Ca{sup 2+}, and at low Ts venom concentrations, the reduction of {sup 3}H-GABA uptake was not as marked as in the presence of Ca{sup 2+}. TsTX-V did not reduce {sup 3}H-GABA uptake in COS-7 cells expressing the GABA transporters GAT-1 and GAT-3, suggesting that this toxin indirectly reduces the transport. The reduced {sup 3}H-GABA uptake by synaptosomes might be due to rapid cell depolarization as revealed by confocal microscopy of C6 glioma cells. Thus, TsTX-V causes a reduction of {sup 3}H-GABA and {sup 3}H-DA uptake in a Ca{sup 2+}-dependent manner, not directly affecting GABA transporters, but, in consequence of depolarization, involving voltage-gated Na{sup +} channels.« less

Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes.

PubMed

Pentassuglia, Laura; Heim, Philippe; Lebboukh, Sonia; Morandi, Christian; Xu, Lifen; Brink, Marijke

2016-05-01

Nrg1β is critically involved in cardiac development and also maintains function of the adult heart. Studies conducted in animal models showed that it improves cardiac performance under a range of pathological conditions, which led to its introduction in clinical trials to treat heart failure. Recent work also implicated Nrg1β in the regenerative potential of neonatal and adult hearts. The molecular mechanisms whereby Nrg1β acts in cardiac cells are still poorly understood. In the present study, we analyzed the effects of Nrg1β on glucose uptake in neonatal rat ventricular myocytes and investigated to what extent mTOR/Akt signaling pathways are implicated. We show that Nrg1β enhances glucose uptake in cardiomyocytes as efficiently as IGF-I and insulin. Nrg1β causes phosphorylation of ErbB2 and ErbB4 and rapidly induces the phosphorylation of FAK (Tyr(861)), Akt (Thr(308) and Ser(473)), and its effector AS160 (Thr(642)). Knockdown of ErbB2 or ErbB4 reduces Akt phosphorylation and blocks the glucose uptake. The Akt inhibitor VIII and the PI3K inhibitors LY-294002 and Byl-719 abolish Nrg1β-induced phosphorylation and glucose uptake. Finally, specific mTORC2 inactivation after knockdown of rictor blocks the Nrg1β-induced increases in Akt-p-Ser(473) but does not modify AS160-p-Thr(642) or the glucose uptake responses to Nrg1β. In conclusion, our study demonstrates that Nrg1β enhances glucose uptake in cardiomyocytes via ErbB2/ErbB4 heterodimers, PI3Kα, and Akt. Furthermore, although Nrg1β activates mTORC2, the resulting Akt-Ser(473) phosphorylation is not essential for glucose uptake induction. These new insights into pathways whereby Nrg1β regulates glucose uptake in cardiomyocytes may contribute to the understanding of its regenerative capacity and protective function in heart failure. Copyright © 2016 the American Physiological Society.

Uncoupling of attenuated myo-(3H)inositol uptake and dysfunction in Na(+)-K(+)-ATPase pumping activity in hypergalactosemic cultured bovine lens epithelial cells

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

Cammarata, P.R.; Tse, D.; Yorio, T.

1991-06-01

Attenuation of both the active transport of myo-inositol and Na(+)-K(+)-ATPase pumping activity has been implicated in the onset of sugar cataract and other diabetic complications in cell culture and animal models of the disease. Cultured bovine lens epithelial cells (BLECs) maintained in galactose-free Eagle's minimal essential medium (MEM) or 40 mM galactose with and without sorbinil for up to 5 days were examined to determine the temporal effects of hypergalactosemia on Na(+)-K(+)-ATPase and myo-inositol uptake. The Na(+)-K(+)-ATPase pumping activity after 5 days of continuous exposure to galactose did not change, as demonstrated by 86Rb uptake. The uptake of myo-(3H)inositol wasmore » lowered after 20 h of incubation in galactose and remained below that of the control throughout the 5-day exposure period. The coadministration of sorbinil to the galactose medium normalized the myo-(3H)inositol uptake. No significant difference in the rates of passive efflux of myo-(3H)inositol or 86Rb from preloaded galactose-treated and control cultures was observed. Culture-media reversal studies were also carried out to determine whether the galactose-induced dysfunction in myo-inositol uptake could be corrected. BLECs were incubated in galactose for 5 days, then changed to galactose-free physiological medium with and without sorbinil for a 1-day recovery period. myo-Inositol uptake was reduced to 34% of control after 6 days of continuous exposure to galactose. Within 24 h of media reversal, myo-inositol uptake returned to or exceeded control values in BLECs switched to either MEM or MEM with sorbinil.2+ reversible and occurred independently of changes in Na(+)-K(+)-ATPase pumping activity in cultured lens epithelium, indicating that the two parameters are not strictly associated and that the deficit in myo-inositol uptake occurs rapidly during hypergalactosemia.« less

Distribution and uptake pathways of organochlorine pesticides in greenhouse and conventional vegetables.

PubMed

Zhang, Anping; Luo, Wenxiu; Sun, Jianqiang; Xiao, Hang; Liu, Weiping

2015-02-01

The application of greenhouse vegetable cultivation has dramatically expanded worldwide during the last several decades. However, little information is available on the distribution and uptake of pesticides in greenhouse vegetables. To bridge this knowledge gap, the present study was initiated to investigate the distribution and uptake of organochlorine pesticides (OCPs) in vegetables from plastic greenhouse and conventional cultivation methods. The uptake pathways of OCPs were not significantly different between these two cultivation methods. The arithmetic means of OCP concentrations in greenhouse vegetables were higher than those in conventional vegetables, although there was no significant difference. This small difference raised the concern of whether the tiny difference could be magnified to a significant difference by bioaccumulation in the food chain. The issue should be addressed by a well-designed scheme in future studies. Copyright © 2014 Elsevier B.V. All rights reserved.

The OprB porin plays a central role in carbohydrate uptake in Pseudomonas aeruginosa.

PubMed Central

Wylie, J L; Worobec, E A

1995-01-01

Using interposon mutagenesis, we have generated strains of Pseudomonas aeruginosa which lack or overexpress the substrate-selective OprB porin of this species. A marked decrease or increase in the initial uptake of glucose by these strains verified the role of OprB in facilitating the diffusion of glucose across the outer membrane of P. aeruginosa. However, we also demonstrated that the loss or overexpression of OprB had a similar effect on the uptake of three other sugars able to support the growth of this bacterium (mannitol, glycerol, and fructose). This effect was restricted to carbohydrate transport; arginine uptake was identical in mutant and wild-type strains. These results indicated that OprB cannot be considered strictly a glucose-selective porin; rather, it acts as a central component of carbohydrate transport and is more accurately described as a carbohydrate-selective porin. PMID:7768797

The OprB porin plays a central role in carbohydrate uptake in Pseudomonas aeruginosa.

PubMed

Wylie, J L; Worobec, E A

1995-06-01

Using interposon mutagenesis, we have generated strains of Pseudomonas aeruginosa which lack or overexpress the substrate-selective OprB porin of this species. A marked decrease or increase in the initial uptake of glucose by these strains verified the role of OprB in facilitating the diffusion of glucose across the outer membrane of P. aeruginosa. However, we also demonstrated that the loss or overexpression of OprB had a similar effect on the uptake of three other sugars able to support the growth of this bacterium (mannitol, glycerol, and fructose). This effect was restricted to carbohydrate transport; arginine uptake was identical in mutant and wild-type strains. These results indicated that OprB cannot be considered strictly a glucose-selective porin; rather, it acts as a central component of carbohydrate transport and is more accurately described as a carbohydrate-selective porin.

Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

PubMed

Van Rie, Annelies; Patel, Monita R; Nana, Mbonze; Vanden Driessche, Koen; Tabala, Martine; Yotebieng, Marcel; Behets, Frieda

2014-03-01

A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100-350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

Competitive inhibition of thyroidal uptake of dietary iodide by perchlorate does not describe perturbations in rat serum total T4 and TSH.

PubMed

McLanahan, Eva D; Andersen, Melvin E; Campbell, Jerry L; Fisher, Jeffrey W

2009-05-01

Perchlorate (ClO4(-)) is an environmental contaminant known to disrupt the thyroid axis of many terrestrial and aquatic species. ClO4(-) competitively inhibits iodide uptake into the thyroid at the sodium/iodide symporter and disrupts hypothalamic-pituitary-thyroid (HPT) axis homeostasis in rodents. We evaluated the proposed mode of action for ClO4(-)-induced rat HPT axis perturbations using a biologically based dose-response (BBDR) model of the HPT axis coupled with a physiologically based pharmacokinetic model of ClO4(-). We configured a BBDR-HPT/ClO4(-) model to describe competitive inhibition of thyroidal uptake of dietary iodide by ClO4(-) and used it to simulate published adult rat drinking water studies. We compared model-predicted serum thyroid-stimulating hormone (TSH) and total thyroxine (TT4) concentrations with experimental observations reported in these ClO4(-) drinking water studies. The BBDR-HPT/ClO4(-) model failed to predict the ClO4(-)-induced onset of disturbances in the HPT axis. Using ClO4(-) inhibition of dietary iodide uptake into the thyroid, the model underpredicted both the rapid decrease in serum TT4 concentrations and the rise in serum TSH concentrations. Assuming only competitive inhibition of thyroidal uptake of dietary iodide, BBDR-HPT/ClO4(-) model calculations were inconsistent with the rapid decrease in serum TT4 and the corresponding increase in serum TSH. Availability of bound iodide in the thyroid gland governed the rate of hormone secretion from the thyroid. ClO4(-) is translocated into the thyroid gland, where it may act directly or indirectly on thyroid hormone synthesis/secretion in the rat. The rate of decline in serum TT4 in these studies after 1 day of treatment with ClO4(-) appeared consistent with a reduction in thyroid hormone production/secretion. This research demonstrates the utility of a biologically based model to evaluate a proposed mode of action for ClO4(-) in a complex biological process.

Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.

PubMed

Avella, Joseph; Kunaparaju, Naveen; Kumar, Sunil; Lehrer, Michael; Zito, S William; Barletta, Michael

2010-09-01

1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in products designed for dusting electronic equipment and air brush painting. When abused, inhaled DFE produces intoxication and loss of muscular coordination. To investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic exposure during abuse, a protocol which has not been conducted. Tissue collection (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120, 240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart 338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38, 0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively. All animals showed signs of intoxication within 20 s manifested as lethargy, prostration and loss of righting reflex. Marked intoxication continued for about 4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8 min, animals continued to show signs of sedation as evidenced by reduced aggression and excitement during handling. No discernable intoxication was evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg, respectively. Plots of concentration (log) versus time were consistent with a two compartment model. Initial distribution was rapid with average half life (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood, 110 s in brain and 168 s in heart. Late elimination half lives were longer with blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1), and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may underestimate these parameters if DFE is abused chronically due to continued uptake into lowly perfused tissues with repeated dosing.

Role of M Cells in Human Mucosal Immunity to Mycobacterium tuberculosis

PubMed Central

Nair, Vidhya; Khan, Haaris; Mitchell, Ron; Shiloh, Michael U

2017-01-01

Abstract Background Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a bacterial pathogen that infects roughly one-third of the worldÕs population and causes 1–2 million deaths per year. The current paradigm is that phagocytosis of Mtb by patrolling alveolar macrophages initiates Mtb infection. While this model can account for pulmonary TB, it does not adequately explain the occurrence of extrapulmonary forms of TB that manifest in the absence of obvious lung involvement, such as tuberculous cervical lymphadenitis, also known as scrofula. We hypothesized that specialized epithelial cells called microfold cells (M cells) may be an alternate portal of entry for Mtb. Previously we demonstrated that Mtb is able to transcytose across an epithelial barrier in an M cell dependent manner and that M cell mediated transcytosis is vital for Mtb pathogenesis in a mouse model of tuberculosis. Methods We used an in vitro M-cell mediated translocation assay and a Mtb mutant lacking a key virulence factor, ESAT6. We used biochemistry and genetics to identify a novel receptor for ESAT6. We also developed a novel explanted human adenoid Mtb infection model to study mucosal immunity. Results We now demonstrate that the Mtb virulence factor ESAT6 is necessary and sufficient to mediate binding and transcytosis by M cells in vitro and in vivo, and that uptake of Mtb by M cells requires a unique cell surface ESAT6 receptor. We developed a novel explanted human adenoid model of M cell biology and demonstrate rapid Mtb transcytosis by primary human tissue within 60–120 minutes. Using flow cytometry we find that Mtb is first ingested by M cells and then after transcytosis, by tissue resident antigen-presenting cells. Explanted adenoids from 10 independent donors display a wide range of Mtb uptake. Conclusion We conclude that Mtb ESAT6 is necessary for Mtb uptake by M-cells and that binding and transcytosis require a host receptor. Because explanted adenoids display a wide range of Mtb uptake, M cell mediated transcytosis may confer differential susceptibility to scrofula and disseminated disease. These findings are significant as M cells could potentially serve as the basis for novel therapeutic targets against primary Mtb infection. Disclosures All authors: No reported disclosures.

Biological characterization of F-18-labeled rhodamine B, a potential positron emission tomography perfusion tracer.

PubMed

Bartholomä, Mark D; He, Huamei; Pacak, Christina A; Dunning, Patricia; Fahey, Frederic H; McGowan, Francis X; Cowan, Douglas B; Treves, S Ted; Packard, Alan B

2013-11-01

Myocardial infarction is the leading cause of death in western countries, and positron emission tomography (PET) plays an increasing role in the diagnosis and treatment planning for this disease. However, the absence of an (18)F-labeled PET myocardial perfusion tracer hampers the widespread use of PET in myocardial perfusion imaging (MPI). We recently reported a potential MPI agent based on (18)F-labeled rhodamine B. The goal of this study was to more completely define the biological properties of (18)F-labeled rhodamine B with respect to uptake and localization in an animal model of myocardial infarction and to evaluate the uptake (18)F-labeled rhodamine B by cardiomyocytes. A total of 12 female Sprague Dawley rats with a permanent ligation of the left anterior descending artery (LAD) were studied with small-animal PET. The animals were injected with 100-150 μCi of (18)F-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) and imaged two days before ligation. The animals were imaged again two to ten days post-ligation. After the post-surgery scans, the animals were euthanized and the hearts were sectioned into 1mm slices and myocardial infarct size was determined by phosphorimaging and 2,3,5-triphenyltetrazolium chloride staining (TTC). In addition, the uptake of [(18)F]RhoBDEGF in isolated rat neonatal cardiomyocytes was determined by fluorescence microscopy. Small-animal PET showed intense and uniform uptake of [(18)F]RhoBDEGF throughout the myocardium in healthy rats. After LAD ligation, well defined perfusion defects were observed in the PET images. The defect size was highly correlated with the infarct size as determined ex vivo by phosphorimaging and TTC staining. In vitro, [(18)F]RhoBDEGF was rapidly internalized into rat cardiomyocytes with ~40 % of the initial activity internalized within the 60 min incubation time. Fluorescence microscopy clearly demonstrated localization of [(18)F]RhoBDEGF in the mitochondria of rat cardiomyocytes. Fluorine-18-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) provides excellent image quality and clear delineation of myocardial infarcts in a rat infarct model. In vitro studies demonstrate localization of the tracer in the mitochondria of cardiac myocytes. In combination, these results support the continued evaluation of this tracer for the PET assessment of myocardial perfusion. © 2013.

Biological Characterization of F-18-Labeled Rhodamine B, a Potential Positron Emission Tomography Perfusion Tracer

PubMed Central

Bartholomä, Mark D.; He, Huamei; Pacak, Christina; Dunning, Patricia; Fahey, Frederic H.; McGowan, Francis; Cowan, Douglas; Treves, S. Ted; Packard, Alan B.

2013-01-01

Introduction Myocardial infarction is the leading cause of death in western countries, and positron emission tomography (PET) plays an increasing role in the diagnosis and treatment planning for this disease. However, the absence of an F-18-labeled PET myocardial perfusion tracer hampers the widespread use of PET in myocardial perfusion imaging (MPI). We recently reported a potential MPI agent based on F-18-labeled rhodamine B. The goal of this study was to more completely define the biological properties of F-18-labeled rhodamine B with respect to uptake and localization in an animal model of myocardial infarction and to evaluate the uptake F-18-labeled rhodamine B by cardiomyocytes. Methods A total of 12 female Sprague Dawley rats with a permanent ligation of the left anterior descending artery (LAD) were studied with small-animal PET. The animals were injected with 100–150 µCi of F-18-labeled rhodamine B diethylene glycol ester ([18F]RhoBDEGF) and imaged two days before ligation. The animals were imaged again two to ten days post-ligation. After the post-surgery scans, the animals were euthanized and the hearts were sectioned into 1 mm slices and myocardial infarct size was determined by phosphorimaging and 2,3,5-triphenyltetrazolium chloride staining (TTC). In addition, the uptake of [18F]RhoBDEGF in isolated rat neonatal cardiomyocytes was determined by fluorescence microscopy. Results Small-animal PET showed intense and uniform uptake of [18F]RhoBDEGF throughout the myocardium in healthy rats. After LAD ligation, well defined perfusion defects were observed in the PET images. The defect size was highly correlated with the infarct size as determined ex vivo by phosphorimaging and TTC staining. In vitro, [18F]RhoBDEGF was rapidly internalized into rat cardiomyocytes with ~40 % of the initial activity internalized within the 60 min incubation time. Fluorescence microscopy clearly demonstrated localization of [18F]RhoBDEGF in the mitochondria of rat cardiomyocytes. Conclusion Fluorine-18-labeled rhodamine B diethylene glycol ester ([18F]RhoBDEGF) provides excellent image quality and clear delineation of myocardial infarcts in a rat infarct model. In vitro studies demonstrate localization of the tracer in the mitochondria of cardiac myocytes. In combination, these results support the continued evaluation of this tracer for the PET assessment of myocardial perfusion. PMID:24011396

Preparation of large porous deslorelin-PLGA microparticles with reduced residual solvent and cellular uptake using a supercritical carbon dioxide process.

PubMed

Koushik, Kavitha; Kompella, Uday B

2004-03-01

The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical carbon dioxide (SC CO2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent. Initial studies with crystalline L-lactide (L-PLA) and amorphous copolymers of lactide-co-glycolide (PLGA) 50:50, 65:35, and 75:25 indicated that PLGA 50:50 was the most amenable to morphological changes upon SC CO2 treatment. Therefore, we prepared deslorelin-PLGA (50:50) microparticles using the conventional emulsion-solvent evaporation method, and in a second step equilibrated with SC CO2 at various temperatures (33-37 degrees C) and pressures (1200-2000 psi) for discrete intervals followed by rapid isothermal depressurization. The particles were then characterized for morphology, polymer thermal properties, particle size, porosity, bulk density, and residual solvent content. Also, deslorelin integrity, conformation, release, and cellular uptake before and after SC CO2 treatment was determined. Upon SC CO2 treatment (1200 psi, 33 degrees C for 30 min), the mean particle size of the deslorelin PLGA microparticles increased from 2.2 to 13.8 microm, the mean porosity increased from 39 to 92.38% the mean pore diameter increased from 90 to 190 nm, the mean bulk density reduced from 0.7 to 0.082 g/cc, mass spectrometry indicated structural integrity of released deslorelin, the circular dichroism spectrum indicated stabilization of beta-turn conformation, and the scanning electron microscopy confirmed increased particle size and pore formation. The deslorelin release was sustained during the 7-day study period. Also, the peak Tg of PLGA decreased from 51 to 45 degrees C, and the residual solvent content was reduced from 4500 ppm to below detection limit (< 25 ppm). The accumulation of drug from SC CO2 treated particles in cell layers of Calu-3, A549, and rat alveolar macrophages was reduced by 87, 91 and 50%, respectively, compared to untreated particles. An SCF-derived process could be successfully applied to prepare large porous deslorelin-PLGA particles with reduced residual solvent content, which retained deslorelin integrity, sustained deslorelin release, and reduced cellular uptake.

Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures.

PubMed

Greenlee, John E; Clawson, Susan A; Hill, Kenneth E; Wood, Blair; Clardy, Stacey L; Tsunoda, Ikuo; Jaskowski, Troy D; Carlson, Noel G

2014-09-17

Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri antibody may diminish following tumor removal or immunosuppression. To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) antibody uptake occurred in living neurons and was not an artifact of antibody diffusion into dead cells; 3) intracellular binding of anti-Hu antibody produced neuronal cell death, whereas uptake of anti-Ri antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of antibody-mediated neuronal death. Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this antibody response. Our results raise questions as to whether anti-Ri antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.

Comparative Physiological Studies of the Yeast and Mycelial Forms of Histoplasma capsulatum: Uptake and Incorporation of l-Leucine

PubMed Central

Gupta, Rishab K.; Howard, Dexter H.

1971-01-01

l-Leucine entered the cells of both morphological forms of Histoplasma capsulatum by a permease-like system at low external concentrations of substrate. However, at levels greater than 5 × 10−5m l-leucine, the amino acid entered the cells both through a simple diffusion-like process and the permease-like system. The rate of the amino acid diffusion into yeast and mycelial forms appeared to be the same, whereas the initial rate of accumulation through the permease-like system was 5 to 10 times faster in the mycelial phase than it was in the yeast phase. The Michaelis constants were 2.2 × 10−5m in yeast phase and 2 × 10−5m in mycelial phase cells. Transport of l-leucine at an external concentration of 10−5m showed all of the characteristics of a system of active transport, which was dependent on temperature and pH. Displacement or removal of the α-amino group, or modification of the α-carboxyl group abolished amino acid uptake. The process was competitively inhibited by neutral aliphatic side-chain amino acids (inhibition constants ranged from 1.5 × 10−5 to 6.2 × 10−5m). Neutral aromatic side-chain amino acids and the d-isomers of leucine and valine did not inhibit l-leucine uptake. These data were interpreted to mean that the l-leucine transport system is stereospecific and is highly specific for neutral aliphatic side-chain amino acids. Incorporation of l-leucine into macromolecules occurred at almost the same rate in both morphological forms of the fungus. The mycelial phase but not the yeast phase showed a slight initial lag in incorporation. In both morphological forms the intracellular pool of l-leucine was of limited capacity, and the total uptake of the amino acid was a function of intracellular pool size. The initial rate of l-leucine uptake was independent of the level of intracellular pool. Both morphological forms deaminated and degraded only a minor fraction of the accumulated leucine. PMID:4323295

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

PubMed

Bailey, J J; Dewaraja, Y; Hubers, D; Srinivasa, R N; Frey, K A

2017-10-01

To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

Effect of pH and calcium on short-term NO3- fluxes in roots of barley seedlings

NASA Technical Reports Server (NTRS)

Aslam, M.; Travis, R. L.; Huffaker, R. C.

1995-01-01

The effect of pH and Ca2+ on net NO3- uptake, influx, and efflux by intact roots of barley (Hordeum vulgare L.) seedlings was studied. Seedlings were induced with NO3- or NO2-. Net NO3- uptake and efflux, respectively, were determined by following its depletion from, and accumulation in, the external solution. Since roots of both uninduced and NO2(-)-induced seedlings contain little internal NO3- initial net uptake rates are equivalent to influx (M. Aslam, R.L. Travis, R.C. Huffaker [1994] Plant Physiol 106: 1293-1301). NO3-, uptake (influx) by these roots was little affected at acidic pH. In contrast, in NO3(-)-induced roots, which accumulate NO3-, net uptake rates decreased in response to acidic pH. Under these conditions, NO3- efflux was stimulated and was a function of root NO3- concentration. Conversely, at basic pH, NO3- uptake by NO3- and NO2(-)-induced and uninduced roots decreased, apparently because of the inhibition of influx. Calcium had little effect on NO3- uptake (influx) by NO2(-)-induced roots at either pH 3 or 6. However, in NO3(-)-induced roots, lack of Ca2+ at pH 3 significantly decreased net NO3- uptake and stimulated efflux. The results indicate that at acidic pH the decrease in net NO3- uptake is due to the stimulation of efflux, whereas at basic pH, it is due to the inhibition of influx.

Substrates and controls for the quantitative detection of active botulinum neurotoxin in protease-containing samples

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins (BoNTs) enjoy a wide variety of medical applications. However, limited pharmacokinetic data on active BoNT is available. Monitoring BoNT activity in the circulation is a challenging task, due to BoNT’s enormous toxicity, rapid neuronal uptake, and removal from the bloodstream. ...

Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation.

PubMed

Konduru, Nagarjun V; Murdaugh, Kimberly M; Swami, Archana; Jimenez, Renato J; Donaghey, Thomas C; Demokritou, Philip; Brain, Joseph D; Molina, Ramon M

2016-08-01

Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated (65)ZnO or silica-coated (65)ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for (65)Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated (65)ZnO were shorter (initial - <1 min; terminal - 2.5 min) than uncoated (65)ZnO (initial - 1.9 min; terminal - 38 min). Interestingly, the silica-coated (65)ZnO group had higher (65)Zn associated with red blood cells and higher initial uptake in the liver. The (65)Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology and nanomedical applications of NPs.

Introduction of the second-generation direct-acting antivirals (DAAs) in chronic hepatitis C: a register-based study in Sweden.

PubMed

Frisk, P; Aggefors, K; Cars, T; Feltelius, N; Loov, S A; Wettermark, B; Weiland, O

2018-07-01

Introduction of the direct-acting antivirals (DAAs) for treatment of chronic hepatitis C (CHC) infection has been challenging in all health systems. In Sweden, a national protocol for managed introduction was developed. It was optional, but all county councils agreed to implement and follow it. The purpose of this study was to study (a) cure rates among all patients initiated on treatment in 2014-2015, (b) prescribers' adherence to the drug recommendations and treatment eligibility criteria in the protocol, and (c) introduction rate in the six Swedish healthcare regions. A cross-sectional study where national data from the Prescribed Drug Register and the quality register InfCare Hepatitis defined the study population, and clinical data from the Patient Register and InfCare Hepatitis were used to monitor outcomes. Descriptive statistics were used. A total of 3447 patients were initiated on treatment during 2014-2015. The overall cure rate, based on data from 85% of the cohort, was 96%, with variation between genotypes. Adherence to drug recommendations increased over time and varied between 43.2 and 94.2%. Adherence to the treatment eligibility criteria was initially 80% and increased to 87% when treatment restrictions were widened. The introduction rate differed initially between the regions and reached stable levels 15-18 months after the launch of the first DAA. The estimated overall cure rate was 96%, with some variations between genotypes. A high level of adherence to the introduction protocol as well as similar introduction rates in the health care regions indicate that the introduction protocol, alongside with other measures taken, contributed considerably to a rapid uptake and equal distribution of DAAs in Sweden.

Chitin nanofibrils for rapid and efficient removal of metal ions from water system.

PubMed

Liu, Dagang; Zhu, Yi; Li, Zehui; Tian, Donglin; Chen, Lei; Chen, Peng

2013-10-15

Joint mechanical defibrillation was successfully used to downsize chitin micro-particles (CMP) into nanofibrils without changing its chemical or crystalline structure. The fine chitin nanofibrils (CNF) bearing width of about 50 nm and length of more than 1 μm were then developed as heavy metal ion sorbents. The uptake performance of CNF dependent on pH, ionic concentration, time, and temperature was investigated. Results show that fixation amount of Cd(II), Ni(II), Cu(II), Zn(II), Pb(II), Cr(III) on CNF was up to 2.94, 2.30, 2.22, 2.06, 1.46, and 0.31 mmol/g, respectively, much higher than CMP due to high specific surface area and widely distributed pores of CNF. Adsorption kinetics of CMP and CNF followed pseudo-second-order model and Freundlich isotherm although CNF exhibited higher rate constant and sorption capacity than that of CMP. The defibrillated CNF is renewable, feasible, easily recyclable, and is thought as good candidate for heavy metal ion treatment due to their low sorption energy, rapid and efficient uptake capacity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rapid screening of selective serotonin re-uptake inhibitors in urine samples using solid-phase microextraction gas chromatography-mass spectrometry.

PubMed

Salgado-Petinal, Carmen; Lamas, J Pablo; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2005-07-01

In this paper a solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method is proposed for a rapid analysis of some frequently prescribed selective serotonin re-uptake inhibitors (SSRI)-venlafaxine, fluvoxamine, mirtazapine, fluoxetine, citalopram, and sertraline-in urine samples. The SPME-based method enables simultaneous determination of the target SSRI after simple in-situ derivatization of some of the target compounds. Calibration curves in water and in urine were validated and statistically compared. This revealed the absence of matrix effect and, in consequence, the possibility of quantifying SSRI in urine samples by external water calibration. Intra-day and inter-day precision was satisfactory for all the target compounds (relative standard deviation, RSD, <14%) and the detection limits achieved were <0.4 ng mL(-1) urine. The time required for the SPME step and for GC analysis (30 min each) enables high throughput. The method was applied to real urine samples from different patients being treated with some of these pharmaceuticals. Some SSRI metabolites were also detected and tentatively identified.

Lipoprotein Uptake by Neuronal Growth Cones in Vitro

NASA Astrophysics Data System (ADS)

Ignatius, Michael J.; Shooter, Eric M.; Pitas, Robert E.; Mahley, Robert W.

1987-05-01

Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.

Mechanism-based pharmacokinetic modeling to evaluate transporter-enzyme interplay in drug interactions and pharmacogenetics of glyburide.

PubMed

Varma, Manthena V S; Scialis, Renato J; Lin, Jian; Bi, Yi-An; Rotter, Charles J; Goosen, Theunis C; Yang, Xin

2014-07-01

The purpose of this study is to characterize the involvement of hepato-biliary transport and cytochrome-P450 (CYP)-mediated metabolism in the disposition of glyburide and predict its pharmacokinetic variability due to drug interactions and genetic variations. Comprehensive in vitro studies suggested that glyburide is a highly permeable drug with substrate affinity to multiple efflux pumps and to organic anion transporting polypeptide (OATP)1B1 and OATP2B1. Active hepatic uptake was found to be significantly higher than the passive uptake clearance (15.8 versus 5.3 μL/min/10(6)-hepatocytes), using the sandwich-cultured hepatocyte model. In vitro, glyburide is metabolized (intrinsic clearance, 52.9 μL/min/mg-microsomal protein) by CYP3A4, CYP2C9, and CYP2C8 with fraction metabolism of 0.53, 0.36, and 0.11, respectively. Using these in vitro data, physiologically based pharmacokinetic models, assuming rapid-equilibrium between blood and liver compartments or permeability-limited hepatic disposition, were built to describe pharmacokinetics and evaluate drug interactions. Permeability-limited model successfully predicted glyburide interactions with rifampicin and other perpetrator drugs. Conversely, model assuming rapid-equilibrium mispredicted glyburide interactions, overall, suggesting hepatic uptake as the primary rate-determining process in the systemic clearance of glyburide. Further modeling and simulations indicated that the impairment of CYP2C9 function has a minimal effect on the systemic exposure, implying discrepancy in the contribution of CYP2C9 to glyburide clearance.

Relationship between oxygen concentration, respiration and filtration rate in blue mussel Mytilus edulis

NASA Astrophysics Data System (ADS)

Tang, Baojun; Riisgård, Hans Ulrik

2018-03-01

The large water-pumping and particle-capturing gills of the filter-feeding blue mussel Mytilus edulis are oversized for respiratory purposes. Consequently, the oxygen uptake rate of the mussel has been suggested to be rather insensitive to decreasing oxygen concentrations in the ambient water, since the diffusion rate of oxygen from water flowing through the mussel determines oxygen uptake. We tested this hypothesis by measuring the oxygen uptake in mussels exposed to various oxygen concentrations. These concentrations were established via N2-bubbling of the water in a respiration chamber with mussels fed algal cells to stimulate fully opening of the valves. It was found that mussels exposed to oxygen concentrations decreasing from 9 to 2 mg O2/L resulted in a slow but significant reduction in the respiration rate, while the filtration rate remained high and constant. Thus, a decrease of oxygen concentration by 78% only resulted in a 25% decrease in respiration rate. However, at oxygen concentrations below 2 mg O2/L M. edulis responded by gradually closing its valves, resulting in a rapid decrease of filtration rate, concurrent with a rapid reduction of respiration rate. These observations indicated that M. edulis is no longer able to maintain its normal aerobic metabolism at oxygen concentration below 2 mg O2/L, and there seems to be an energy-saving mechanism in bivalve molluscs to strongly reduce their activity when exposed to low oxygen conditions.

Equilibrium and Kinetic Studies of Cd2+ Biosorption by the Brown Algae Sargassum fusiforme

PubMed Central

Zou, Hui-Xi; Li, Nan; Wang, Li-Hua; Yu, Ping; Yan, Xiu-Feng

2014-01-01

A fundamental investigation of the biosorption of Cd2+ from aqueous solution by the edible seaweed Sargassum fusiforme was performed under batch conditions. The influences of experimental parameters, such as the initial pH, sorption time, temperature, and initial Cd2+ concentration, on Cd2+ uptake by S. fusiforme were evaluated. The results indicated that the biosorption of Cd2+ depended on the initial Cd2+ concentration, as well as the pH. The uptake of Cd2+ could be described by the Langmuir isotherm model, and both the Langmuir biosorption equilibrium constant and the maximum biosorption capacity of the monolayer decreased with increasing temperature, thereby confirming the exothermic character of the sorption process. The biosorption kinetics follows the pseudo-second-order kinetic model, and intraparticle diffusion is the sole rate-limiting step for the entire biosorption period. These fundamental equilibrium and kinetic results can support further studies to the removal of cadmium from S. fusiforme harvested from cadmium-polluted waters. PMID:24736449

Expression and Function of Thyroid Hormone Transporters in the Microvillous Plasma Membrane of Human Term Placental Syncytiotrophoblast

PubMed Central

Loubière, L. S.; Vasilopoulou, E.; Glazier, J. D.; Taylor, P. M.; Franklyn, J. A.; Kilby, M. D.

2012-01-01

The transplacental passage of thyroid hormones (THs) from mother to fetus in humans has been deduced from observational clinical studies and is important for normal fetoplacental development. To investigate the transporters that regulate TH uptake by syncytiotrophoblast (the primary barrier to maternal-fetal exchange, which lies in direct contact with maternal blood), we isolated the microvillous plasma membrane (MVM) of human term syncytiotrophoblasts. We have demonstrated that MVM vesicles express plasma membrane TH transporter proteins, including system-L (L-type amino acid transporter 1 and CD98), monocarboxylate transporters (MCTs) 8 and 10, organic anion-transporting polypeptides 1A2 and 4A1. We provide the first definitive evidence that the human syncytiotrophoblast MVM is capable of rapid, saturable T4 and T3 uptake at similar rates and in a Na+-independent manner. These two major forms of THs could not significantly inhibit each others' uptake, suggesting that each is mediated by largely different transporters. No single transporter was noted to play a dominant role in either T4 or T3 uptake. Using combinations of transporter inhibitors that had an additive effect on TH uptake, we provide evidence that 67% of saturable T4 uptake is facilitated by system-L and MCT10 with a minor role played by organic anion-transporting polypeptides, whereas 87% of saturable T3 uptake is mediated by MCT8 and MCT10. Our data demonstrate that syncytiotrophoblast may control the quantity and forms of THs taken up by the human placenta. Thus, syncytiotrophoblast could be critical in regulating transplacental TH supply from the mother to the fetus. PMID:23087173

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects.

PubMed

Morrison, G C; Weschler, C J; Bekö, G

2016-12-01

To better understand the dermal exposure pathway, we enhance an existing mechanistic model of transdermal uptake by including skin surface lipids (SSL) and consider the impact of clothing. Addition of SSL increases the overall resistance to uptake of SVOCs from air but also allows for rapid transfer of SVOCs to sinks like clothing or clean air. We test the model by simulating di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) exposures of six bare-skinned (Weschler et al. 2015, Environ. Health Perspect., 123, 928) and one clothed participant (Morrison et al. 2016, J. Expo. Sci. Environ. Epidemiol., 26, 113). The model predicts total uptake values that are consistent with the measured values. For bare-skinned participants, the model predicts a normalized mass uptake of DEP of 3.1 (μg/m 2 )/(μg/m 3 ), whereas the experimental results range from 1.0 to 4.3 (μg/m 2 )/(μg/m 3 ); uptake of DnBP is somewhat overpredicted: 4.6 (μg/m 2 )/(μg/m 3 ) vs. the experimental range of 0.5-3.2 (μg/m 2 )/(μg/m 3 ). For the clothed participant, the model predicts higher than observed uptake for both species. Uncertainty in model inputs, including convective mass transfer coefficients, partition coefficients, and diffusion coefficients, could account for overpredictions. Simulations that include transfer of skin oil to clothing improve model predictions. A dynamic model that includes SSL is more sensitive to changes that impact external mass transfer such as putting on and removing clothes and bathing. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Uptake of 4-chloro-2-methylphenoxyacetic acid (MCPA) from the apical membrane of Caco-2 cells by the monocarboxylic acid transporter

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

Kimura, Osamu; Tsukagoshi, Kensuke; Endo, Tetsuya

2008-03-15

The cellular uptake mechanism of 4-chloro-2-methylphenoxyacetic acid (MCPA), a phenoxyacetic acid derivative, was investigated using Caco-2 epithelial cells. The cells were incubated with 50 {mu}M MCPA at pH 6.0 and 37 deg. C, and the uptake of MCPA from the apical membranes was measured. The uptake of MCPA was significantly decreased by incubation at low temperature (4 {sup o}C) and markedly increased by lowering the extracellular pH. Pretreatment with a protonophore, carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone (25 {mu}M), or metabolic inhibitors, 2,4-dinitrophenol (1 mM) and sodium azide (10 mM), significantly decreased the uptake of MCPA by 53%, 45% and 48%, respectively. Coincubation of MCPAmore » with 10 mM L-lactic acid or {alpha}-cyano-4-hydroxycinnamate, which is a substrate or an inhibitor of the monocarboxylic acid transporters (MCTs), significantly decreased the uptake of MCPA by 31% and 20%, respectively, and coincubation with benzoic acid profoundly decreased the uptake by 68%. In contrast, coincubation with succinic acid (a dicarboxylic acid) did not affect the uptake. Kinetic analysis of initial MCPA uptake suggested that MCPA is taken up via a carrier-mediated process [K{sub m} = 1.37 {+-} 0.15 mM, V{sub max} = 115 {+-} 6 nmol (mg protein){sup -1} (3 min){sup -1}]. Lineweaver-Burk plots show that benzoic acid competitively inhibits the uptake of MCPA with a K{sub i} value of 4.68 {+-} 1.76 mM. A trans-stimulation effect on MCPA uptake was found in cells preloaded with benzoic acid. These results suggest that the uptake of MCPA from the apical membrane of Caco-2 cells is mainly mediated by common MCTs along with benzoic acid but also in part by L-lactic acid.« less

Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Aggarwal, Sameer; Passah, Averilicia; Behera, Abhishek; Arora, Geetanjali; Bal, Chandrasekhar; Tripathi, Madhavi

2018-06-01

We present here a case of metastatic adrenocortical carcinoma with bilateral lung nodules. The patient had been treated with mitotane therapy initially and then was later referred for chemotherapy. There was progression of disease noted on the F-FDG PET/CT. Ga prostate-specific membrane antigen (PSMA) PET/CT was planned to explore the possibility of future treatment with Lu-DKFZ-PSMA-617. It revealed peripheral increased uptake of Ga-HBED-CC-PSMA equal to liver uptake.

Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

PubMed

Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2017-01-17

A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P < 0.001). Autoradiography and histochemical staining results were consistent with selective uptake of the radiotracer in the necrotic regions. Among the these tracers, 99m Tc(EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with 77.61% decline at 1 h after coinjection. These findings suggested 99m Tc(EDDA)-HYNIC-2C-rhein emerged as a "hot spot" imaging probe that has a potential for rapid imaging of necrotic myocardium. The necrosis avidity mechanism of 99m Tc(EDDA)-HYNIC-linker-rhein may be due to its interaction with exposed DNA in necrotic tissues.

Phosphorus cycling and partitioning in an oligotrophic Everglades wetland ecosystem: A radioisotope tracing study

USGS Publications Warehouse

Noe, G.B.; Scinto, L.J.; Taylor, J.; Childers, D.L.; Jones, R.D.

2003-01-01

1. Our goal was to quantify short-term phosphorus (P) partitioning and identify the ecosystem components important to P cycling in wetland ecosystems. To do this, we added P radiotracer to oligotrophic, P-limited Everglades marshes. 32PO4 was added to the water column in six 1-m2 enclosed mesocosms located in long-hydroperiod marshes of Shark River Slough, Everglades National Park. Ecosystem components were then repeatedly sampled over 18 days. 2. Water column particulates (>0.45 ??m) incorporated radiotracer within the first minute after dosing and stored 95-99% of total water column 32P activity throughout the study. Soluble (<0.45 ??m) 32P in the water column, in contrast, was always <5% of the 32P in surface water. Periphyton, both floating and attached to emergent macrophytes, had the highest specific activity of 32P (Bq g-131P) among the different ecosystem components. Fish and aquatic macroinvertebrates also had high affinity for P, whereas emergent macrophytes, soil and flocculent detrital organic matter (floc) had the lowest specific activities of radiotracer. 3. Within the calcareous, floating periphyton mats, 81% of the initial 32P uptake was associated with Ca, but most of this 32P entered and remained within the organic pool (Ca-associated = 14% of total) after 1 day. In the floc layer, 32P rapidly entered the microbial pool and the labile fraction was negligible for most of the study. 4. Budgeting of the radiotracer indicated that 32P moved from particulates in the water column to periphyton and floc and then to the floc and soil over the course of the 18 days incubations. Floc (35% of total) and soil (27%) dominated 32P storage after 18 days, with floating periphyton (12%) and surface water (10%) holding smaller proportions of total ecosystem 32P. 5. To summarise, oligotrophic Everglades marshes exhibited rapid uptake and retention of labile 32P. Components dominated by microbes appear to control short-term P cycling in this oligotrophic ecosystem.

Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle

PubMed Central

Launikonis, Bradley S; Stephenson, D George; Friedrich, Oliver

2009-01-01

Periods of low frequency stimulation are known to increase the net Ca2+ uptake in skeletal muscle but the mechanism responsible for this Ca2+ entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca2+ flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca2+ in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca2+] ([Ca2+]t-sys) and cytoplasmic [Ca2+] ([Ca2+]cyto) were simultaneously resolved on a confocal microscope. When initial [Ca2+]t-sys was ≥ 0.2 mm a Ca2+ flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca2+ flux and associated t-system Ca2+ permeability decayed exponentially and displayed inactivation characteristics such that further Ca2+ entry across the t-system could not be observed after 2–3 action potentials at 10 Hz stimulation rate. When [Ca2+]t-sys was closer to 0.1 mm, a transient rise in [Ca2+]t-sys was observed almost concurrently with the increase in [Ca2+]cyto following the action potential. The change in direction of Ca2+ flux was consistent with changes in the direction of the driving force for Ca2+. This is the first demonstration of a rapid t-system Ca2+ flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca2+ channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca2+ flux provides an explanation for the previously described Ca2+ entry and accumulation observed with prolonged, intermittent muscle activity. PMID:19332499

Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses.

PubMed

Chen, Ping; Hübner, Wolfgang; Spinelli, Matthew A; Chen, Benjamin K

2007-11-01

Cell-free human immunodeficiency virus type 1 (HIV-1) can initiate infections, but contact between infected and uninfected T cells can enhance viral spread through intercellular structures called virological synapses (VS). The relative contribution of VS to cell-free viral transfer has not been carefully measured. Using an ultrasensitive, fluorescent virus transfer assay, we estimate that when VS between HIV-expressing Jurkat T cells and primary CD4(+) T cells are formed, cell-associated transfer of virus is 18,000-fold more efficient than uptake of cell-free virus. Furthermore, in contrast to cell-free virus uptake, the VS deposits virus rapidly into focal, trypsin-resistant compartments in target T cells. This massive virus internalization requires Env-CD4 receptor interactions but is resistant to inhibition by patient-derived neutralizing antisera that inhibit homologous cell-free virus. Deleting the Env cytoplasmic tail does not abrogate VS-mediated transfer, but it renders the VS sensitive to neutralizing antibodies, suggesting that the tail limits exposure of VS-neutralizing epitopes on the surface of infected cells. Dynamic live imaging of the VS reveals that HIV-expressing cells are polarized and make sustained, Env-dependent contacts with target cells through uropod-like structures. The polarized T-cell morphology, Env-CD4 coordinated adhesion, and viral transfer from HIV-infected to uninfected cells suggest that VS allows HIV-1 to evade antibody neutralization and to disseminate efficiently. Future studies will discern to what extent this massive viral transfer contributes to productive infection or viral dissemination through the migration of virus-carrying T cells.

Two Major Facilitator Superfamily Sugar Transporters from Trichoderma reesei and Their Roles in Induction of Cellulase Biosynthesis*

PubMed Central

Zhang, Weixin; Kou, Yanbo; Xu, Jintao; Cao, Yanli; Zhao, Guolei; Shao, Jing; Wang, Hai; Wang, Zhixing; Bao, Xiaoming; Chen, Guanjun; Liu, Weifeng

2013-01-01

Proper perception of the extracellular insoluble cellulose is key to initiating the rapid synthesis of cellulases by cellulolytic Trichoderma reesei. Uptake of soluble oligosaccharides derived from cellulose hydrolysis represents a potential point of control in the induced cascade. In this study, we identified a major facilitator superfamily sugar transporter Stp1 capable of transporting cellobiose by reconstructing a cellobiose assimilation system in Saccharomyces cerevisiae. The absence of Stp1 in T. reesei resulted in differential cellulolytic response to Avicel versus cellobiose. Transcriptional profiling revealed a different expression profile in the Δstp1 strain from that of wild-type strain in response to Avicel and demonstrated that Stp1 somehow repressed induction of the bulk of major cellulase and hemicellulose genes. Two other putative major facilitator superfamily sugar transporters were, however, up-regulated in the profiling. Deletion of one of them identified Crt1 that was required for growth and enzymatic activity on cellulose or lactose, but was not required for growth or hemicellulase activity on xylan. The essential role of Crt1 in cellulase induction did not seem to rely on its transporting activity because the overall uptake of cellobiose or sophorose by T. reesei was not compromised in the absence of Crt1. Phylogenetic analysis revealed that orthologs of Crt1 exist in the genomes of many filamentous ascomycete fungi capable of degrading cellulose. These data thus shed new light on the mechanism by which T. reesei senses and transmits the cellulose signal and offers potential strategies for strain improvement. PMID:24085297

Molecular Dynamics Simulations for Loading-Dependent Diffusion of CO2, SO2, CH4, and Their Binary Mixtures in ZIF-10: The Role of Hydrogen Bond.

PubMed

Li, Li; Yang, Deshuai; Fisher, Trevor R; Qiao, Qi; Yang, Zhen; Hu, Na; Chen, Xiangshu; Huang, Liangliang

2017-10-24

The loading-dependent diffusion behavior of CH 4 , CO 2 , SO 2 , and their binary mixtures in ZIF-10 has been investigated in detail by using classical molecular dynamics simulations. Our simulation results demonstrate that the self-diffusion coefficient D i of CH 4 molecules decreases sharply and monotonically with the loading while those of both CO 2 and SO 2 molecules initially display a slight increase at low uptakes and follow a slow decrease at high uptakes. Accordingly, the interaction energies between CH 4 molecules and ZIF-10 remain nearly constant regardless of the loading due to the absence of hydrogen bonds (HBs), while the interaction energies between CO 2 (or SO 2 ) and ZIF-10 decease rapidly with the loading, especially at small amounts of gas molecules. Such different loading-dependent diffusion and interaction mechanisms can be attributed to the relevant HB behavior between gas molecules and ZIF-10. At low loadings, both the number and strength of HBs between CO 2 (or SO 2 ) molecules and ZIF-10 decrease obviously as the loading increases, which is responsible for the slight increase of their diffusion coefficients. However, at high loadings, their HB strength increases with the loading. Similar loading-dependent phenomena of diffusion, interaction, and HB behavior can be observed for CH 4, CO 2 , and SO 2 binary mixtures in ZIF-10, only associated with some HB competition between CO 2 and SO 2 molecules in the case of the CO 2 /SO 2 mixture.

Effect of intravascular-to-extravascular water exchange on the determination of blood-to-tissue transfer constant by magnetic resonance imaging.

PubMed

Cao, Y; Brown, S L; Knight, R A; Fenstermacher, J D; Ewing, J R

2005-02-01

Water exchange across capillary walls couples intra- and extravascular (IV-EV) protons and their magnetization. A bolus i.v. injection of an extracellular MRI contrast agent (MRCA) causes a large increase in the spin-lattice relaxation rate, R1, of water protons in the plasma and blood cells within the capillaries and changes the effective relaxation rate R1eff in tissue via IV-EV water exchange. An analysis of the effect of plasma-red cell and IV-EV water exchange on the MRI-measured influx and permeability of capillaries to the MRCA is presented and focused on the brain and the blood-brain barrier. The effect of arrival of a bolus of an MRCA in the capillary on the relaxation rate R1eff in tissue via IV-EV water exchange occurs more rapidly than the MRCA uptake in tissue and can dominate the initial time curve of the R1eff change before the MRCA uptake in tissue becomes significant. This raises the possibility that (tissue dependent) IV-EV rate of exchange of water molecules can affect estimates of MRCA transfer constant. We demonstrate that an approach that considers IV-EV water exchange and uses the theoretical model of blood-brain tracer distribution developed by Patlak et al. (J Cereb Blood Flow Metab 1983;3:1-7) can lead to an accurate estimate of the MRI-determined influx rate constant of the MRCA and to an underestimation of the tissue blood volume.

Self-amplifying mRNA vaccines.

PubMed

Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

2015-01-01

This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

PubMed Central

Okesola, Nonhlanhla; Tanser, Frank; Thiebaut, Rodolphe; Rekacewicz, Claire; Newell, Marie-Louise

2016-01-01

Background The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART. Methods and Findings Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded. Conclusions Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population. Trial registration ClinicalTrials.gov NCT01509508 PMID:27504637

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial.

PubMed

Iwuji, Collins C; Orne-Gliemann, Joanna; Larmarange, Joseph; Okesola, Nonhlanhla; Tanser, Frank; Thiebaut, Rodolphe; Rekacewicz, Claire; Newell, Marie-Louise; Dabis, Francois

2016-08-01

The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART. Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded. Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population. ClinicalTrials.gov NCT01509508.

Small-animal PET of steroid hormone receptors predicts tumor response to endocrine therapy using a preclinical model of breast cancer.

PubMed

Fowler, Amy M; Chan, Szeman Ruby; Sharp, Terry L; Fettig, Nicole M; Zhou, Dong; Dence, Carmen S; Carlson, Kathryn E; Jeyakumar, M; Katzenellenbogen, John A; Schreiber, Robert D; Welch, Michael J

2012-07-01

Estrogen receptor-α (ERα) and progesterone receptor (PR) are expressed in most human breast cancers and are important predictive factors for directing therapy. Because of de novo and acquired resistance to endocrine therapy, there remains a need to identify which ERα-positive (ERα(+))/PR-positive (PR(+)) tumors are most likely to respond. The purpose of this study was to use estrogen- and progestin-based radiopharmaceuticals to image ERα and PR in mouse mammary tumors at baseline and after hormonal therapy and to determine whether changes in these imaging biomarkers can serve as an early predictive indicator of therapeutic response. Mammary adenocarcinomas that spontaneously develop in aged female mice deficient in signal transducer and activator of transcription-1 (STAT1) were used. Imaging of ERα and PR in primary tumor-bearing mice and mice implanted with mammary cell lines (SSM1, SSM2, and SSM3) derived from primary STAT1-deficient (STAT1(-/-)) tumors was performed. Hormonal treatments consisted of estradiol, an ER agonist; letrozole, an aromatase inhibitor; and fulvestrant, a pure ER antagonist. Small-animal PET/CT was performed using (18)F-fluoroestradiol ((18)F-FES) for ER, (18)F-fluoro furanyl norprogesterone ((18)F-FFNP) for PR, and (18)F-FDG for glucose uptake. Tracer uptake in the tumor was quantified and compared with receptor concentration determined by in vitro assays of resected tumors. Primary STAT1(-/-) mammary tumors and implanted SSM2 and SSM3 tumors showed high (18)F-FES and (18)F-FFNP uptake and were confirmed to be ERα(+)/PR(+). Classic estrogen-induced regulation of the progesterone receptor gene was demonstrated by increased (18)F-FFNP uptake of estradiol-treated SSM3 tumors. Treatment with fulvestrant decreased (18)F-FFNP, (18)F-FES, and (18)F-FDG uptake and inhibited growth of SSM3 tumors but decreased only (18)F-FES uptake in SSM2 tumors, with no effect on growth, despite both tumors being ERα(+)/PR(+). Decreased (18)F-FFNP uptake by SSM3 tumors occurred early after initiation of treatment, before measurable tumor growth inhibition. Using small-animal PET, a profile was identified that distinguished fulvestrant-sensitive from fulvestrant-resistant ERα(+)/PR(+) tumors before changes in tumor size. This work demonstrates that imaging baseline tumoral (18)F-FES uptake and initial changes in (18)F-FFNP uptake in a noninvasive manner is a potentially useful strategy to identify responders and nonresponders to endocrine therapy at an early stage.

Size-dependent lymphatic uptake of nanoscale-tailored particles as tumor mass increases.

PubMed

Kjellman, Pontus; Fredriksson, Sarah; Kjellman, Christian; Strand, Sven-Erik; Zandt, René In 't

2015-11-01

To investigate the size-dependent lymphatic uptake of nanoparticles in mice with rapidly growing syngeneic tumors. Mice were inoculated subcutaneously with EL4 lymphoma cells and on day 5 or day 6 of tumor growth, injected peritumorally with either 29 nm or 58 nm of ultra-small superparamagnetic iron oxide nanoparticles. Twenty-four hours later the animals were imaged using MRI. The larger of the two particles can only be detected in the lymph node when injected in animals with 6-day-old tumors while the 29 nm ultra-small superparamagnetic iron oxide nanoparticle is observed on both time points. Tumor mass greatly impacts the size of particles that are transported to the lymph nodes.

Nanomolar Copper Enhances Mercury Methylation by Desulfovibrio desulfuricans ND132

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

Lu, Xia; Johs, Alexander; Zhao, Linduo

Methylmercury (MeHg) is produced by certain anaerobic microorganisms, such as the sulfate-reducing bacterium Desulfovibrio desulfuricans ND132, but environmental factors affecting inorganic mercury [Hg(II)] uptake and methylation remain unclear. We report that the presence of a small amount of copper ions [Cu(II), <100 nM] enhances Hg(II) uptake and methylation by washed cells of ND132, while Hg(II) methylation is inhibited at higher Cu(II) concentrations because of the toxicity of copper to the microorganism. The enhancement or inhibitory effect of Cu(II) is dependent on both time and concentration. The presence of nanomolar concentrations of Cu(II) facilitates rapid uptake of Hg(II) (within minutes) andmore » doubles MeHg production within a 24 h period, but micromolar concentrations of Cu(II) completely inhibit Hg(II) methylation. Metal ions such as zinc [Zn(II)] and nickel [Ni(II)] also inhibit but do not enhance Hg(II) methylation under the same experimental conditions. Furthermore, these observations suggest a synergistic effect of Cu(II) on Hg(II) uptake and methylation, possibly facilitated by copper transporters or metallochaperones in this organism, and highlight the fact that complex environmental factors affect MeHg production in the environment.« less

Uptake and Function Studies of Maternal Milk-derived MicroRNAs*

PubMed Central

Title, Alexandra C.; Denzler, Rémy; Stoffel, Markus

2015-01-01

MicroRNAs (miRNAs) are important regulators of cell-autonomous gene expression that influence many biological processes. They are also released from cells and are present in virtually all body fluids, including blood, urine, saliva, sweat, and milk. The functional role of nutritionally obtained extracellular miRNAs is controversial, and irrefutable demonstration of exogenous miRNA uptake by cells and canonical miRNA function is still lacking. Here we show that miRNAs are present at high levels in the milk of lactating mice. To investigate intestinal uptake of miRNAs in newborn mice, we employed genetic models in which newborn miR-375 and miR-200c/141 knockout mice received milk from wild-type foster mothers. Analysis of the intestinal epithelium, blood, liver, and spleen revealed no evidence for miRNA uptake. miR-375 levels in hepatocytes were at the limit of detection and remained orders of magnitude below the threshold for target gene regulation (between 1000 and 10,000 copies/cell). Furthermore, our study revealed rapid degradation of milk miRNAs in intestinal fluid. Together, our results indicate a nutritional rather than gene-regulatory role of miRNAs in the milk of newborn mice. PMID:26240150

Diadenosine tetraphosphate (Ap4A) induces a diabetogenic situation: its impact on blood glucose, plasma insulin, gluconeogenesis, glucose uptake and GLUT-4 transporters.

PubMed

Verspohl, E J; Hohmeier, N; Lempka, M

2003-12-01

Diadenosine polyphosphates such as Ap4A are physiologically released compounds for which both receptors as well as a role as second messengers for influencing insulin release have been shown. So far little is known about their pathophysiological impact on diabetes with respect to blood glucose and plasma insulin, glucose production via gluconeogenesis, glucose uptake and GLUT-4 expression. Rats given an intravenous bolus of Ap4A (0.75 mg/kg) developed a rapid and dramatic increase in blood glucose. Plasma insulin was only transiently increased (for 4 min), but did not follow the normally stimulatory effect of the elevated blood glucose. A bolus of 25 microg Ap4A quickly increased glucose release from perfused rat liver. Glucose uptake was reduced in 3T3 adipocytes. Reduced amounts of translocated GLUT-4 were found in 3T3 cell membranes incubated with 10 microM Ap4A. Thus, Ap4A itself induces a diabetic situation which is likely to be mediated by an increase in gluconeogenesis and/or an insulin resistance caused by a decrease in GLUT-4 and an attenuation of glucose uptake.

Radical loss in the atmosphere from Cu-Fe redox coupling in aerosols

NASA Astrophysics Data System (ADS)

Mao, J.; Fan, S.; Jacob, D. J.; Travis, K.; Naik, V.; Horowitz, L. W.

2012-12-01

The hydroperoxyl radical (HO2) is a major precursor of OH and tropospheric ozone. OH is the main atmospheric oxidant, while tropospheric ozone is an important surface pollutant and greenhouse gas. Standard gas-phase models for atmospheric chemistry tend to overestimate observed HO2 concentrations, and this has been tentatively attributed to heterogeneous uptake by aerosol particles. It is generally assumed that HO2 uptake by aerosol involves conversion to H2O2, but this is of limited efficacy as an HO2 sink because H2O2 can photolyze to regenerate OH and from there HO2. Joint atmospheric observations of HO2 and H2O2 suggest that HO2 uptake by aerosols may in fact not produce H2O2. Here we propose a catalytic mechanism involving coupling of the transition metal ions (TMI) Cu(I)/Cu(II) and Fe(II)/Fe(III) to rapidly convert HO2 to H2O in aerosols. The implied HO2 uptake significantly affects global model predictions of tropospheric OH, ozone, and other species, improving comparisons to observations, and may have a major and previously unrecognized impact on atmospheric oxidant chemistry.

Nanomolar Copper Enhances Mercury Methylation by Desulfovibrio desulfuricans ND132

DOE PAGES

Lu, Xia; Johs, Alexander; Zhao, Linduo; ...

2018-05-29

Methylmercury (MeHg) is produced by certain anaerobic microorganisms, such as the sulfate-reducing bacterium Desulfovibrio desulfuricans ND132, but environmental factors affecting inorganic mercury [Hg(II)] uptake and methylation remain unclear. We report that the presence of a small amount of copper ions [Cu(II), <100 nM] enhances Hg(II) uptake and methylation by washed cells of ND132, while Hg(II) methylation is inhibited at higher Cu(II) concentrations because of the toxicity of copper to the microorganism. The enhancement or inhibitory effect of Cu(II) is dependent on both time and concentration. The presence of nanomolar concentrations of Cu(II) facilitates rapid uptake of Hg(II) (within minutes) andmore » doubles MeHg production within a 24 h period, but micromolar concentrations of Cu(II) completely inhibit Hg(II) methylation. Metal ions such as zinc [Zn(II)] and nickel [Ni(II)] also inhibit but do not enhance Hg(II) methylation under the same experimental conditions. Furthermore, these observations suggest a synergistic effect of Cu(II) on Hg(II) uptake and methylation, possibly facilitated by copper transporters or metallochaperones in this organism, and highlight the fact that complex environmental factors affect MeHg production in the environment.« less

3D glasma initial state for relativistic heavy ion collisions

DOE PAGES

Schenke, Björn; Schlichting, Sören

2016-10-13

We extend the impact-parameter-dependent Glasma model to three dimensions using explicit small-x evolution of the two incoming nuclear gluon distributions. We compute rapidity distributions of produced gluons and the early-time energy momentum tensor as a function of space-time rapidity and transverse coordinates. Finally, we study rapidity correlations and fluctuations of the initial geometry and multiplicity distributions and make comparisons to existing models for the three-dimensional initial state.

Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo.

PubMed

Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

2016-08-11

The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods-intrauterine devices (IUDs) and implants-in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher training for providers on how to insert IUDs to strengthen their competence and confidence. Over time, we noted a gradual redistribution of the method mix in parallel with vigorous continued family planning uptake. This experience suggests that analyzing method mix can be helpful for designing program strategies and that expanding method choice can accelerate satisfying demand, especially in environments with high unmet need for contraception. © Rattan et al.

Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo

PubMed Central

Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

2016-01-01

ABSTRACT The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods—intrauterine devices (IUDs) and implants—in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher training for providers on how to insert IUDs to strengthen their competence and confidence. Over time, we noted a gradual redistribution of the method mix in parallel with vigorous continued family planning uptake. This experience suggests that analyzing method mix can be helpful for designing program strategies and that expanding method choice can accelerate satisfying demand, especially in environments with high unmet need for contraception. PMID:27540125

Microbial utilization of low molecular weight organics in soil depends on the substances properties

NASA Astrophysics Data System (ADS)

Gunina, Anna

2016-04-01

Utilization of low molecular weight organic substances (LMWOS) in soil is regulated by microbial uptake from solution and following incorporation of into specific cell cycles. Various chemical properties of LMWOS, namely oxidation state, number of carbon (C) atoms, number of carboxylic (-COOH) groups, can affect their uptake from soil solution and further microbial utilization. The aim of the study was to trace the initial fate (including the uptake from soil solution and utilization by microorganisms) of three main classes of LMWOS, having contrast properties - sugars, carboxylic and amino acids. Top 10 cm of mineral soil were collected under Silver birch stands within the Bangor DIVERSE experiment, UK. Soil solution was extracted by centrifugation at 4000 rpm during 15 min. Soil was spiked with 14C glucose or fructose; malic, succinic or formic acids; alanine or glycine. No additional non-labeled LMWOS were added. 14C was traced in the dissolved organic matter (DOM), CO2, cytosol and soil organic matter (SOM) during one day. To estimate half-life times (T1 /2)of LMWOS in soil solution and in SOM pools, the single and double first order kinetic equations were fitted to the uptake and mineralization dynamics, respectively. The LMWOS T1 /2in DOM pool varied between 0.6-5 min, with the highest T1 /2for sugars (3.7 min) and the lowest for carboxylic acids (0.6-1.4 min). Thus, initial uptake of LMWOS is not a limiting step of microbial utilization. The T1 /2 of carboxylic and amino acids in DOM were closely related with oxidation state, showing that reduced substances remain in soil solution longer, than oxidized. The initial T1 /2 of LMWOS in SOM ranged between 30-80 min, with the longest T1 /2 for amino acids (50-80 min) and the shortest for carboxylic acids (30-48 min). These T1 /2values were in one-two orders of magnitude higher than LMWOS T1 /2 in soil solution, pointing that LMWOS mineralization occur with a delay after the uptake. Absence of correlations between LMWOS T1 /2 in SOM with C oxidation state, number of C atoms or number of -COOH groups in LMWOS demonstrates that intercellular metabolic pathways are more important. Mineralization of LMWOS amounted for 20-90% of total applied amount. Maximum mineralization was found for carboxylic acids and minimum for sugars, whereas 14C incorporation into cytosol and SOM pools followed the opposite trend. There were close positive correlation between the portion of mineralized C and substance oxidation state, but negative with the amount of C incorporated into the cytosol and SOM pools. This shows that substance properties affect the final partitioning of LMWOS-C between mineralized and utilized pools. Thus, initial uptake of LMWOS from soil solution and final partitioning of LMWOS-C between the mineralized and microbially utilized pools are related to their chemical properties. In contrast, LMWOS mineralization dynamics is regulated by intercellular metabolization pathways.

Effect of acute alarm odor exposure and biological sex on generalized avoidance and glutamatergic signaling in the hippocampus of Wistar rats.

PubMed

Homiack, Damek; O'Cinneide, Emma; Hajmurad, Sema; Dohanich, Gary P; Schrader, Laura A

2018-06-19

Post-traumatic stress disorder (PTSD) is characterized by the development of paradoxical memory disturbances including intrusive memories and amnesia for specific details of the traumatic experience. Despite evidence that women are at higher risk to develop PTSD, most animal research has focused on the processes by which male rodents develop adaptive fear memory. As such, the mechanisms contributing to sex differences in the development of PTSD-like memory disturbances are poorly understood. In this investigation, we exposed adult male and female Wistar rats to the synthetic alarm odor 2,4,5-trimethylthiazole (TMT) to assess development of generalized fear behavior and rapid modulation of glutamate uptake and signaling cascades associated with hippocampus-dependent long-term memory. We report that female Wistar rats exposed to alarm odor exhibit context discrimination impairments relative to TMT-exposed male rats, suggesting the intriguing possibility that females are at greater risk in developing generalized fear memories. Mechanistically, alarm odor exposure rapidly modulated signaling cascades consistent with activation of the CREB shut-off cascade in the male, but not the female hippocampus. Moreover, TMT exposure dampened glutamate uptake and affected expression of the glutamate transporter, GLT-1 in the hippocampus. Taken together, these results provide evidence for rapid sex-dependent modulation of CREB signaling in the hippocampus by alarm odor exposure which may contribute to the development of generalized fear.

Sustainable, Rapid Synthesis of Bright-Luminescent CuInS2-ZnS Alloyed Nanocrystals: Multistage Nano-xenotoxicity Assessment and Intravital Fluorescence Bioimaging in Zebrafish-Embryos

NASA Astrophysics Data System (ADS)

Chetty, S. Shashank; Praneetha, S.; Basu, Sandeep; Sachidanandan, Chetana; Murugan, A. Vadivel

2016-05-01

Near-infrared (NIR) luminescent CuInS2-ZnS alloyed nanocrystals (CIZS-NCs) for highly fluorescence bioimaging have received considerable interest in recent years. Owing, they became a desirable alternative to heavy-metal based-NCs and organic dyes with unique optical properties and low-toxicity for bioimaging and optoelectronic applications. In the present study, bright and robust CIZS-NCs have been synthesized within 5 min, as-high-as 230 °C without requiring any inert-gas atmosphere via microwave-solvothermal (MW-ST) method. Subsequently, the in vitro and in vivo nano-xenotoxicity and cellular uptake of the MUA-functionalized CIZS-NCs were investigated in L929, Vero, MCF7 cell lines and zebrafish-embryos. We observed minimal toxicity and acute teratogenic consequences upto 62.5 μg/ml of the CIZS-NCs in zebrafish-embryos. We also observed spontaneous uptake of the MUA-functionalized CIZS-NCs by 3 dpf older zebrafish-embryos that are evident through bright red fluorescence-emission at a low concentration of 7.8 μg/mL. Hence, we propose that the rapid, low-cost, large-scale “sustainable” MW-ST synthesis of CIZS-NCs, is an ideal bio-nanoprobe with good temporal and spatial resolution for rapid labeling, long-term in vivo tracking and intravital-fluorescence-bioimaging (IVBI).

Gill remodelling during terrestrial acclimation reduces aquatic respiratory function of the amphibious fish Kryptolebias marmoratus.

PubMed

Turko, Andy J; Cooper, Chris A; Wright, Patricia A

2012-11-15

The skin-breathing amphibious fish Kryptolebias marmoratus experiences rapid environmental changes when moving between water- and air-breathing, but remodelling of respiratory morphology is slower (~1 week). We tested the hypotheses that (1) there is a trade-off in respiratory function of gills displaying aquatic versus terrestrial morphologies and (2) rapidly increased gill ventilation is a mechanism to compensate for reduced aquatic respiratory function. Gill surface area, which varied inversely to the height of the interlamellar cell mass, was increased by acclimating fish for 1 week to air or low ion water, or decreased by acclimating fish for 1 week to hypoxia (~20% dissolved oxygen saturation). Fish were subsequently challenged with acute hypoxia, and gill ventilation or oxygen uptake was measured. Fish with reduced gill surface area increased ventilation at higher dissolved oxygen levels, showed an increased critical partial pressure of oxygen and suffered impaired recovery compared with brackish water control fish. These results indicate that hyperventilation, a rapid compensatory mechanism, was only able to maintain oxygen uptake during moderate hypoxia in fish that had remodelled their gills for land. Thus, fish moving between aquatic and terrestrial habitats may benefit from cutaneously breathing oxygen-rich air, but upon return to water must compensate for a less efficient branchial morphology (mild hypoxia) or suffer impaired respiratory function (severe hypoxia).

Nanofiber Ion-Exchange Membranes for the Rapid Uptake and Recovery of Heavy Metals from Water

PubMed Central

Chitpong, Nithinart; Husson, Scott M.

2016-01-01

An evaluation of the performance of polyelectrolyte-modified nanofiber membranes was undertaken to determine their efficacy in the rapid uptake and recovery of heavy metals from impaired waters. The membranes were prepared by grafting poly(acrylic acid) (PAA) and poly(itaconic acid) (PIA) to cellulose nanofiber mats. Performance measurements quantified the dynamic ion-exchange capacity for cadmium (Cd), productivity, and recovery of Cd(II) from the membranes by regeneration. The dynamic binding capacities of Cd(II) on both types of nanofiber membrane were independent of the linear flow velocity, with a residence time of as low as 2 s. Analysis of breakthrough curves indicated that the mass flow rate increased rapidly at constant applied pressure after membranes approached equilibrium load capacity for Cd(II), apparently due to a collapse of the polymer chains on the membrane surface, leading to an increased porosity. This mechanism is supported by hydrodynamic radius (Rh) measurements for PAA and PIA obtained from dynamic light scattering, which show that Rh values decrease upon Cd(II) binding. Volumetric productivity was high for the nanofiber membranes, and reached 0.55 mg Cd/g/min. The use of ethylenediaminetetraacetic acid as regeneration reagent was effective in fully recovering Cd(II) from the membranes. Ion-exchange capacities were constant over five cycles of binding-regeneration. PMID:27999394

Nanofiber Ion-Exchange Membranes for the Rapid Uptake and Recovery of Heavy Metals from Water.

PubMed

Chitpong, Nithinart; Husson, Scott M

2016-12-20

An evaluation of the performance of polyelectrolyte-modified nanofiber membranes was undertaken to determine their efficacy in the rapid uptake and recovery of heavy metals from impaired waters. The membranes were prepared by grafting poly(acrylic acid) (PAA) and poly(itaconic acid) (PIA) to cellulose nanofiber mats. Performance measurements quantified the dynamic ion-exchange capacity for cadmium (Cd), productivity, and recovery of Cd(II) from the membranes by regeneration. The dynamic binding capacities of Cd(II) on both types of nanofiber membrane were independent of the linear flow velocity, with a residence time of as low as 2 s. Analysis of breakthrough curves indicated that the mass flow rate increased rapidly at constant applied pressure after membranes approached equilibrium load capacity for Cd(II), apparently due to a collapse of the polymer chains on the membrane surface, leading to an increased porosity. This mechanism is supported by hydrodynamic radius (R h ) measurements for PAA and PIA obtained from dynamic light scattering, which show that R h values decrease upon Cd(II) binding. Volumetric productivity was high for the nanofiber membranes, and reached 0.55 mg Cd/g/min. The use of ethylenediaminetetraacetic acid as regeneration reagent was effective in fully recovering Cd(II) from the membranes. Ion-exchange capacities were constant over five cycles of binding-regeneration.

Validation of a rapid, semiautomatic image analysis tool for measurement of gastric accommodation and emptying by magnetic resonance imaging

PubMed Central

Dixit, Sudeepa; Fox, Mark; Pal, Anupam

2014-01-01

Magnetic resonance imaging (MRI) has advantages for the assessment of gastrointestinal structures and functions; however, processing MRI data is time consuming and this has limited uptake to a few specialist centers. This study introduces a semiautomatic image processing system for rapid analysis of gastrointestinal MRI. For assessment of simpler regions of interest (ROI) such as the stomach, the system generates virtual images along arbitrary planes that intersect the ROI edges in the original images. This generates seed points that are joined automatically to form contours on each adjacent two-dimensional image and reconstructed in three dimensions (3D). An alternative thresholding approach is available for rapid assessment of complex structures like the small intestine. For assessment of dynamic gastrointestinal function, such as gastric accommodation and emptying, the initial 3D reconstruction is used as reference to process adjacent image stacks automatically. This generates four-dimensional (4D) reconstructions of dynamic volume change over time. Compared with manual processing, this semiautomatic system reduced the user input required to analyze a MRI gastric emptying study (estimated 100 vs. 10,000 mouse clicks). This analysis was not subject to variation in volume measurements seen between three human observers. In conclusion, the image processing platform presented processed large volumes of MRI data, such as that produced by gastric accommodation and emptying studies, with minimal user input. 3D and 4D reconstructions of the stomach and, potentially, other gastrointestinal organs are produced faster and more accurately than manual methods. This system will facilitate the application of MRI in gastrointestinal research and clinical practice. PMID:25540229

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

PubMed

Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

2016-02-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin

PubMed Central

Wagner, Mark C.; Campos-Bilderback, Silvia B.; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M.; Wean, Sarah E.; Wei, Yuan; Satlin, Lisa M.; Wiggins, Roger C.; Witzmann, Frank A.

2016-01-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. PMID:26054544

Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients.

PubMed

Schlumberger, Martin; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Bidart, Jean-Michel

2007-03-01

The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

Factors influencing uptake and retention of amino-containing drugs in large unilamellar vesicles exhibiting transmembrane pH gradients.

PubMed

Maurer-Spurej, E; Wong, K F; Maurer, N; Fenske, D B; Cullis, P R

1999-01-12

The level of uptake and retention of amino-containing drugs in large unilamellar vesicles (LUVs) following uptake in response to a transmembrane pH gradient (DeltapH) can vary dramatically depending on the drug. For example, the anticancer drugs doxorubicin and epirubicin can be readily retained, whereas the anticancer drug vincristine and the antibiotic ciprofloxacin tend to leak out rapidly. In this investigation, we examine the influence of the hydrophobicity of the entrapped amines (that induce the DeltapH) and the anionic lipid content of the LUV on drug retention. It is shown that entrapment of increasingly hydrophobic monoamines (methylamine to amylamine) all lead to an induced DeltapH of 3 units and essentially complete drug uptake under the conditions employed, but do not lead to improved retention of vincristine and ciprofloxacin. However, significantly improved retention could be achieved by substitution of the anionic lipid distearoylphosphatidylglycerol (DSPG) for distearoylphosphatidylcholine (DSPC) in the LUV bilayer. Further, it is shown that if the induced DeltapH is reduced to 1.4 units (driven by entrapped diamine) nearly 100% accumulation of doxorubicin and epirubicin could be achieved, whereas only 25% loading for vincristine and ciprofloxacin was observed. Taken together these results provide methodology for improving (weak base) drug retention in liposomes and indicate that drugs that can partition into the lipid bilayer exhibit improved uptake and retention characteristics.

Lymphatic trafficking kinetics and near-infrared imaging using star polymer architectures with controlled anionic character

PubMed Central

Bagby, Taryn R.; Cai, Shuang; Duan, Shaofeng; Yang, Qiuhong; Thati, Sharadvi; Berkland, Cory; Aires, Daniel J.; Forrest, M. Laird

2015-01-01

Targeted lymphatic delivery of nanoparticles for drug delivery and imaging is primarily dependent on size and charge. Prior studies have observed increased lymphatic uptake and retentions of over 48 hrs for negatively charged particles compared to neutral and positively charged particles. We have developed new polymeric materials that extend retention over a more pharmaceutically relevant 7-day period. We used whole body fluorescence imaging to observe in mice the lymphatic trafficking of a series of anionic star poly-(6-O-methacryloyl-D-galactose) polymer-NIR dye (IR820) conjugates. The anionic charge of polymers was increased by modifying galactose moieties in the star polymers with succinic anhydride. Increasing anionic nature was associated with enhanced lymphatic uptake up to a zeta potential of ca. -40 mV; further negative charge did not affect lymphatic uptake. Compared to the 20% acid-conjugate, the 40 to 90% acid-star-polymer conjugates exhibited a 2.5- to 3.5-fold increase in lymphatic uptake in both the popliteal and iliac nodes. The polymer conjugates exhibited node half-lives of 2 to 20 hrs in the popliteal nodes and 19 to 114 hrs in the deeper iliac nodes. These polymer conjugates can deliver drugs or imaging agents with rapid lymphatic uptake and prolonged deep-nodal retention; thus they may provide a useful vehicle for sustained intralymphatic drug delivery with low toxicity. PMID:22546180

Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

PubMed Central

Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

2011-01-01

Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At twelve weeks of age, brain uptake of tail vein-injected 3H-2-deoxy glucose in Glut3+/− mice was not different from Glut3+/+ littermates, despite 50% less Glut3 protein expression in the brain. The brain uptake of injected 18F-2-fluoro-2-deoxy glucose was similarly not different from Glut3+/− littermates in the total amount, time course, or brain imaging in the Glut3+/− mice. Glut1 and Glut6 protein expressions evaluated by immunoblots were not affected by the diminished Glut3 expression in the Glut3+/− mice. We conclude that a 50% decrease in Glut3 is not limiting for the uptake of glucose into the mouse brain, since Glut3 haploinsufficiency does not impair brain glucose uptake or utilization. PMID:21316350

Quantitation of methylglyoxal bis(guanylhydrazone) in blood plasma and leukemia cells of patients receiving the drug.

PubMed

Seppänen, P; Alhonen-Hongisto, L; Siimes, M; Jänne, J

1980-11-15

Methylglyoxal bis(guanylhydrazone), a cytostatic compound which apparently interferes with the metabolism and/or functions of the natural polyamines (spermidine and spermine), was effectively taken up by cultured human lymphocytic leukemia cells, rapidly resulting in the formation of a concentration gradient of up to 1,000-fold across the cell membrane in cells grown in the presence of micromolar concentrations of the drug. For an anti-proliferative effect on the leukemia cells, an intracellular concentration of more than 0.5 mM was required. The uptake of methylglyoxal bis(guanylhydrazone) was critically dependent on the growth rate of the leukemia cells. Low intracellular concentrations of the drug were present in cells growing slowly, whereas in rapidly dividing cells the intracellular concentration of the drug approached 5mM. When given as repeated intravenous infusions to two leukemic children, methylglyoxal bis(guanylhydrazone) exhibited sharp and transient peaks of plasma concentration, the drug having an apparent half-life in plasma of only 1-2 h. However, as in cultured cells, the drug was rapidly concentrated in the leukemia cells, reaching concentrations that were distinctly anti-proliferative. In contrast to the rapid disappearance of methylglyoxal bis(guanylhydrazone) from plasma, the circulation leukemia cells retained the drug for a period of several days with only minimal decrease in the initial concentrations. Methylglyoxal bis(guanylhydrazone) was given to the patients for 1 to 2 months as intravenous infusions, the timing of which was determined by regular assays of the drug concentrations in the leukemia cells. In agreement with the results obtained with the cultured cells, and intracellular concentration of about 0.5 to 1mM was apparently required for growth-inhibitory action to occur. Regular determination of the cellular drug concentrations indicated that methylglyoxal bis(quanylhydrazone) could be given as weekly infusions. This treatment schedule represents much lower dosing of the drug than the earlier daily regimens which were commonly associated with unacceptable toxicity.

In vitro degradation, flexural, compressive and shear properties of fully bioresorbable composite rods.

PubMed

Felfel, R M; Ahmed, I; Parsons, A J; Walker, G S; Rudd, C D

2011-10-01

Several studies have investigated self-reinforced polylactic acid (SR-PLA) and polyglycolic acid (SR-PGA) rods which could be used as intramedullary (IM) fixation devices to align and stabilise bone fractures. This study investigated totally bioresorbable composite rods manufactured via compression moulding at ~100 °C using phosphate glass fibres (of composition 50P(2)O(5)-40CaO-5Na(2)O-5Fe(2)O(3) in mol%) to reinforce PLA with an approximate fibre volume fraction (v(f)) of 30%. Different fibre architectures (random and unidirectional) were investigated and pure PLA rods were used as control samples. The degradation profiles and retention of mechanical properties were investigated and PBS was selected as the degradation medium. Unidirectional (P50 UD) composite rods had 50% higher initial flexural strength as compared to PLA and 60% higher in comparison to the random mat (P50 RM) composite rods. Similar initial profiles for flexural modulus were also seen comparing the P50 UD and P50 RM rods. Higher shear strength properties were seen for P50 UD in comparison to P50 RM and PLA rods. However, shear stiffness values decreased rapidly (after a week) whereas the PLA remained approximately constant. For the compressive strength studies, P50 RM and PLA rods remained approximately constant, whilst for the P50 UD rods a significantly higher initial value was obtained, which decreased rapidly after 3 days immersion in PBS. However, the mechanical properties decreased after immersion in PBS as a result of the plasticisation effect of water within the composite and degradation of the fibres. The fibres within the random and unidirectional composite rods (P50 RM and P50 UD) degraded leaving behind microtubes as seen from the SEM micrographs (after 28 days degradation) which in turn created a porous structure within the rods. This was the main reason attributed for the increase seen in mass loss and water uptake for the composite rods (~17% and ~16%, respectively). Copyright © 2011 Elsevier Ltd. All rights reserved.

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer

PubMed Central

Hoover, Clare E.; Davenport, Kristen A.; Henderson, Davin M.; Denkers, Nathaniel D.; Mathiason, Candace K.; Soto, Claudio; Zabel, Mark D.

2017-01-01

ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrPCWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state. PMID:28250130

Accumulation of phenanthrene by roots of intact wheat (Triticum acstivnm L.) seedlings: passive or active uptake?

PubMed Central

2010-01-01

Background Polycyclic aromatic hydrocarbons (PAHs) are of particular concern due to their hydrophobic, recalcitrant, persistent, potentially carcinogenic, mutagenic and toxic properties, and their ubiquitous occurrence in the environment. Most of the PAHs in the environment are present in surface soil. Plants grown in PAH-contaminated soils or water can become contaminated with PAHs because of their uptake. Therefore, they may threaten human and animal health. However, the mechanism for PAHs uptake by crop roots is little understood. It is important to understand exactly how PAHs are transported into the plant root system and into the human food chain, since it is beneficial in governing crop contamination by PAHs, remedying soils or waters polluted by PAHs with plants, and modeling potential uptake for risk assessment. Results The possibility that plant roots may take up phenanthrene (PHE), a representative of PAHs, via active process was investigated using intact wheat (Triticum acstivnm L.) seedlings in a series of hydroponic experiments. The time course for PHE uptake into wheat roots grown in Hoagland solution containing 5.62 μM PHE for 36 h could be separated into two periods: a fast uptake process during the initial 2 h and a slow uptake component thereafter. Concentration-dependent PHE uptake was characterized by a smooth, saturable curve with an apparent Km of 23.7 μM and a Vmax of 208 nmol g-1 fresh weight h-1, suggesting a carrier-mediated uptake system. Competition between PHE and naphthalene for their uptake by the roots further supported the carrier-mediated uptake system. Low temperature and 2,4-dinitrophenol (DNP) could inhibit PHE uptake equally, indicating that metabolism plays a role in PHE uptake. The inhibitions by low temperature and DNP were strengthened with increasing concentration of PHE in external solution within PHE water solubility (7.3 μM). The contribution of active uptake to total absorption was almost 40% within PHE water solubility. PHE uptake by wheat roots caused an increase in external solution pH, implying that wheat roots take up PHE via a PHE/nH+ symport system. Conclusion It is concluded that an active, carrier-mediated and energy-consuming influx process is involved in the uptake of PHE by plant roots. PMID:20307286

Uptake of DNA by cancer cells without a transfection reagent.

PubMed

Kong, Yanping; Zhang, Xianbo; Zhao, Yongliang; Xue, Yanfang; Zhang, Ye

2017-01-21

Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting reagent.

Extracellular Enzymes Facilitate Electron Uptake in Biocorrosion and Bioelectrosynthesis

PubMed Central

Deutzmann, Jörg S.; Sahin, Merve

2015-01-01

ABSTRACT Direct, mediator-free transfer of electrons between a microbial cell and a solid phase in its surrounding environment has been suggested to be a widespread and ecologically significant process. The high rates of microbial electron uptake observed during microbially influenced corrosion of iron [Fe(0)] and during microbial electrosynthesis have been considered support for a direct electron uptake in these microbial processes. However, the underlying molecular mechanisms of direct electron uptake are unknown. We investigated the electron uptake characteristics of the Fe(0)-corroding and electromethanogenic archaeon Methanococcus maripaludis and discovered that free, surface-associated redox enzymes, such as hydrogenases and presumably formate dehydrogenases, are sufficient to mediate an apparent direct electron uptake. In genetic and biochemical experiments, we showed that these enzymes, which are released from cells during routine culturing, catalyze the formation of H2 or formate when sorbed to an appropriate redox-active surface. These low-molecular-weight products are rapidly consumed by M. maripaludis cells when present, thereby preventing their accumulation to any appreciable or even detectable level. Rates of H2 and formate formation by cell-free spent culture medium were sufficient to explain the observed rates of methane formation from Fe(0) and cathode-derived electrons by wild-type M. maripaludis as well as by a mutant strain carrying deletions in all catabolic hydrogenases. Our data collectively show that cell-derived free enzymes can mimic direct extracellular electron transfer during Fe(0) corrosion and microbial electrosynthesis and may represent an ecologically important but so far overlooked mechanism in biological electron transfer. PMID:25900658

Localization of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene (TNT) in poplar and switchgrass plants using phosphor imager autoradiography.

PubMed

Brentner, Laura B; Mukherji, Sachiyo T; Walsh, Susan A; Schnoor, Jerald L

2010-02-01

Phosphor imager autoradiography is a technique for rapid, sensitive analysis of the localization of xenobiotics in plant tissues. Use of this technique is relatively new to research in the field of plant science, and the potential for enhancing visualization and understanding of plant uptake and transport of xenobiotics remains largely untapped. Phosphor imager autoradiography is used to investigate the uptake and translocation of the explosives 1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene within Populus deltoides x nigra DN34 (poplar) and Panicum vigratum Alamo (switchgrass). In both plant types, TNT and/or TNT-metabolites remain predominantly in root tissues while RDX and/or RDX-metabolites are readily translocated to leaf tissues. Phosphor imager autoradiography is further investigated for use in semi-quantitative analysis of uptake of TNT by switchgrass. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells

PubMed Central

Angela, Mulki; Endo, Yusuke; Asou, Hikari K.; Yamamoto, Takeshi; Tumes, Damon J.; Tokuyama, Hirotake; Yokote, Koutaro; Nakayama, Toshinori

2016-01-01

To fulfil the bioenergetic requirements for increased cell size and clonal expansion, activated T cells reprogramme their metabolic signatures from energetically quiescent to activated. However, the molecular mechanisms and essential components controlling metabolic reprogramming in T cells are not well understood. Here, we show that the mTORC1–PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4+ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4+ T cells. PPARγ directly binds and induces genes associated with fatty acid uptake in CD4+ T cells in both mice and humans. The PPARγ-dependent fatty acid uptake programme is critical for metabolic reprogramming. Thus, we provide important mechanistic insights into the metabolic reprogramming mechanisms that govern the expression of key enzymes, fatty acid metabolism and the acquisition of an activated phenotype during CD4+ T cell activation. PMID:27901044

Metabolism of triacetin-derived acetate in dogs.

PubMed

Bleiberg, B; Beers, T R; Persson, M; Miles, J M

1993-12-01

Triacetin is a water-soluble triglyceride that may have a role as a parenteral nutrient. In the present study triacetin was administered intravenously to mongrel dogs (n = 10) 2 wk after surgical placement of blood-sampling catheters in the aorta and in the portal, hepatic, renal, and femoral veins. [1-14C]Acetate was infused to allow quantification of organ uptake of acetate as well as systemic turnover and oxidation. Systemic acetate turnover accounted for approximately 70% of triacetin-derived acetate, assuming complete hydrolysis of the triglyceride. Approximately 80% of systemic acetate uptake was rapidly oxidized. Significant acetate uptake was demonstrated in all tissues (liver, 559 +/- 68; intestine, 342 +/- 23; hindlimb, 89 +/- 7; and kidney, 330 +/- 37 mumol/min). In conclusion, during intravenous administration in dogs, the majority of infused triacetin undergoes intravascular hydrolysis, and the majority of the resulting acetate is oxidized. Thus, energy in the form of short-chain fatty acids can be delivered to a resting gut via intravenous infusion of a short-chain triglyceride.

Clinical and Psychosocial Factors Influencing Retinal Screening Uptake Among Young Adults with Type 2 Diabetes.

PubMed

Lake, A J; Rees, G; Speight, J

2018-05-24

Young adults with type 2 diabetes (T2D, 18-39 years) experience early-onset and rapid progression of diabetic retinopathy (DR), the leading cause of vision loss for working age adults. Despite this, uptake of retinal screening, the crucial first step in preventing vision loss from DR, is low. The aim of this review is to summarize the clinical and psychosocial factors affecting uptake of retinal screening. Barriers include lack of diabetes-related symptoms, low personal DR risk perception, high rates of depression and diabetes-related distress, fatalism about inevitability of complications, time and financial constraints, disengagement with existing diabetes self-management services, and perceived stigma due to having a condition associated with older adults. Young adults with T2D are an under-researched population who face an accumulation of barriers to retinal screening. Tailored interventions that address the needs, characteristics, and priorities of young adults with T2D are warranted.

Incorporation of nanoparticles into polymersomes: size and concentration effects.

PubMed

Jaskiewicz, Karmena; Larsen, Antje; Schaeffel, David; Koynov, Kaloian; Lieberwirth, Ingo; Fytas, George; Landfester, Katharina; Kroeger, Anja

2012-08-28

Because of the rapidly growing field of nanoparticles in therapeutic applications, understanding and controlling the interaction between nanoparticles and membranes is of great importance. While a membrane is exposed to nanoparticles its behavior is mediated by both their biological and physical properties. Constant interplay of these biological and physicochemical factors makes selective studies of nanoparticles uptake demanding. Artificial model membranes can serve as a platform to investigate physical parameters of the process in the absence of any biofunctional molecules and/or supplementary energy. Here we report on photon- and fluorescence-correlation spectroscopic studies of the uptake of nanosized SiO(2) nanoparticles by poly(dimethylsiloxane)-block-poly(2-methyloxazoline) vesicles allowing species selectivity. Analogous to the cell membrane, polymeric membrane incorporates particles using membrane fission and particles wrapping as suggested by cryo-TEM imaging. It is revealed that the incorporation process can be controlled to a significant extent by changing nanoparticles size and concentration. Conditions for nanoparticle uptake and controlled filling of polymersomes are presented.

The role of community acceptance over time for costs of HIV and STI prevention interventions: analysis of the Masaka Intervention Trial, Uganda, 1996-1999.

PubMed

Terris-Prestholt, Fern; Kumaranayake, Lilani; Foster, Susan; Kamali, Anatoli; Kinsman, John; Basajja, Vincent; Nalweyso, Nora; Quigley, Maria; Kengeya-Kayondo, Jane; Whitworth, James

2006-10-01

The objective of this study is to estimate the annual costs of information, education, and communication (IEC), both community- and school-based; strengthened public and private sexually transmitted infections treatment; condom social marketing (CSM); and voluntary counseling and testing (VCT) implemented in Masaka, Uganda, over 4 years, and to explore how unit costs change with varying population use/uptake. Total economic provider's costs and intervention outputs were collected annually to estimate annual unit costs between 1996 and 1999. In early intervention years, uptake of all activities grew dramatically and continued to grow for public STI treatment, CSM, and VCT. Attendance at IEC performances started to drop in year 4. Unit costs dropped rapidly with increasing uptake of and participation in interventions. When implementing long-term community-based interventions, it is important to take into account that it takes time for communities to scale up their participation, since this can lead to large variations in unit costs.

Dynamical initial-state model for relativistic heavy-ion collisions

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

Shen, Chun; Schenke, Bjorn

We present a fully three-dimensional model providing initial conditions for energy and net-baryon density distributions in heavy ion collisions at arbitrary collision energy. The model includes the dynamical deceleration of participating nucleons or valence quarks, depending on the implementation. The duration of the deceleration continues until the string spanned between colliding participants is assumed to thermalize, which is either after a fixed proper time, or a uctuating time depending on sampled final rapidities. Energy is deposited in space-time along the string, which in general will span a range of space-time rapidities and proper times. We study various observables obtained directlymore » from the initial state model, including net-baryon rapidity distributions, 2-particle rapidity correlations, as well as the rapidity decorrelation of the transverse geometry. Their dependence on the model implementation and parameter values is investigated. Here, we also present the implementation of the model with 3+1 dimensional hydrodynamics, which involves the addition of source terms that deposit energy and net-baryon densities produced by the initial state model at proper times greater than the initial time for the hydrodynamic simulation.« less

Dynamical initial-state model for relativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Shen, Chun; Schenke, Björn

2018-02-01

We present a fully three-dimensional model providing initial conditions for energy and net-baryon density distributions in heavy-ion collisions at arbitrary collision energy. The model includes the dynamical deceleration of participating nucleons or valence quarks, depending on the implementation. The duration of the deceleration continues until the string spanned between colliding participants is assumed to thermalize, which is either after a fixed proper time, or a fluctuating time depending on sampled final rapidities. Energy is deposited in space time along the string, which in general will span a range of space-time rapidities and proper times. We study various observables obtained directly from the initial-state model, including net-baryon rapidity distributions, two-particle rapidity correlations, as well as the rapidity decorrelation of the transverse geometry. Their dependence on the model implementation and parameter values is investigated. We also present the implementation of the model with 3+1-dimensional hydrodynamics, which involves the addition of source terms that deposit energy and net-baryon densities produced by the initial-state model at proper times greater than the initial time for the hydrodynamic simulation.

Dynamical initial-state model for relativistic heavy-ion collisions

DOE PAGES

Shen, Chun; Schenke, Bjorn

2018-02-15

We present a fully three-dimensional model providing initial conditions for energy and net-baryon density distributions in heavy ion collisions at arbitrary collision energy. The model includes the dynamical deceleration of participating nucleons or valence quarks, depending on the implementation. The duration of the deceleration continues until the string spanned between colliding participants is assumed to thermalize, which is either after a fixed proper time, or a uctuating time depending on sampled final rapidities. Energy is deposited in space-time along the string, which in general will span a range of space-time rapidities and proper times. We study various observables obtained directlymore » from the initial state model, including net-baryon rapidity distributions, 2-particle rapidity correlations, as well as the rapidity decorrelation of the transverse geometry. Their dependence on the model implementation and parameter values is investigated. Here, we also present the implementation of the model with 3+1 dimensional hydrodynamics, which involves the addition of source terms that deposit energy and net-baryon densities produced by the initial state model at proper times greater than the initial time for the hydrodynamic simulation.« less

Optimization of scan initiation timing after 11C-methionine administration for the diagnosis of suspected recurrent brain tumors.

PubMed

Nakajima, Reiko; Abe, Koichiro; Momose, Mitsuru; Fukushima, Kenji; Matsuo, Yuka; Kimura, Ken; Kondo, Chisato; Sakai, Shuji

2017-02-01

11 C-Methionine (MET) positron emission tomography (PET) imaging is a valuable technique for the evaluation of primary and recurrent brain tumors. Many studies have used MET-PET for data acquisition starting at 20 min after the tracer injection, while others have used scan initiation times at 5-15 min postinjection. No previous studies have identified the best acquisition timing during MET-PET imaging for suspected recurrent brain tumors. Here we sought to determine the optimal scan initiating timing after MET administration for the detection of recurrent brain tumors. Twenty-three consecutive patients with suspected recurrent brain tumors underwent MET-PET examinations. Brain PET images were reconstructed from the four serial data sets (10-15, 15-20, 20-25, and 25-30 min postinjection) that were obtained using the list-mode acquisition technique. We determined the maximal standardized uptake values (SUVmax) of the target lesions and the target-to-normal-tissue ratios (TNRs), calculated as the SUVmax to the SUVmean of a region of interest placed on the normal contralateral frontal cortex. Target lesions without significant MET uptake were excluded. Thirty-one lesions from 23 patients were enrolled. There were no significant differences in MET SUVmax or TNR values among the PET images that were reconstructed with the data extracted from the four phases postinjection. The MET uptake in the suspected recurrent brain tumors was comparable among all data extraction time phases from 10 to 30 min postinjection. The scan initiation time of MET-PET at 10 min after the injection is allowable for the detection of recurrent brain tumors. The registration identification number of the original study is 1002.

Modernizing and transforming medical education at the Kilimanjaro Christian Medical University College.

PubMed

Lisasi, Esther; Kulanga, Ahaz; Muiruri, Charles; Killewo, Lucy; Fadhili, Ndimangwa; Mimano, Lucy; Kapanda, Gibson; Tibyampansha, Dativa; Ibrahim, Glory; Nyindo, Mramba; Mteta, Kien; Kessi, Egbert; Ntabaye, Moshi; Bartlett, John

2014-08-01

The Kilimanjaro Christian Medical University (KCMU) College and the Medical Education Partnership Initiative (MEPI) are addressing the crisis in Tanzanian health care manpower by modernizing the college's medical education with new tools and techniques. With a $10 million MEPI grant and the participation of its partner, Duke University, KCMU is harnessing the power of information technology (IT) to upgrade tools for students and faculty. Initiatives in eLearning have included bringing fiber-optic connectivity to the campus, offering campus-wide wireless access, opening student and faculty computer laboratories, and providing computer tablets to all incoming medical students. Beyond IT, the college is also offering wet laboratory instruction for hands-on diagnostic skills, team-based learning, and clinical skills workshops. In addition, modern teaching tools and techniques address the challenges posed by increasing numbers of students. To provide incentives for instructors, a performance-based compensation plan and teaching awards have been established. Also for faculty, IT tools and training have been made available, and a medical education course management system is now being widely employed. Student and faculty responses have been favorable, and the rapid uptake of these interventions by students, faculty, and the college's administration suggests that the KCMU College MEPI approach has addressed unmet needs. This enabling environment has transformed the culture of learning and teaching at KCMU College, where a path to sustainability is now being pursued.

Modernizing and Transforming Medical Education at the Kilimanjaro Christian Medical University College

PubMed Central

Lisasi, Esther; Kulanga, Ahaz; Muiruri, Charles; Killewo, Lucy; Fadhili, Ndimangwa; Mimano, Lucy; Kapanda, Gibson; Tibyampansha, Dativa; Ibrahim, Glory; Nyindo, Mramba; Mteta, Kien; Kessi, Egbert; Ntabaye, Moshi; Bartlett, John

2014-01-01

The Kilimanjaro Christian Medical University (KCMU) College and the Medical Education Partnership Initiative (MEPI) are addressing the crisis in Tanzanian health care manpower by modernizing the college’s medical education with new tools and techniques. With a $10 million MEPI grant and the participation of its partner, Duke University, KCMU is harnessing the power of information technology (IT) to upgrade tools for students and faculty. Initiatives in eLearning have included bringing fiber-optic connectivity to the campus, offering campus-wide wireless access, opening student and faculty computer laboratories, and providing computer tablets to all incoming medical students. Beyond IT, the college is also offering wet laboratory instruction for hands-on diagnostic skills, team-based learning, and clinical skills workshops. In addition, modern teaching tools and techniques address the challenges posed by increasing numbers of students. To provide incentives for instructors, a performance-based compensation plan and teaching awards have been established. Also for faculty, IT tools and training have been made available, and a medical education course management system is now being widely employed. Student and faculty responses have been favorable, and the rapid uptake of these interventions by students, faculty, and the college’s administration suggests that the KCMU College MEPI approach has addressed unmet needs. This enabling environment has transformed the culture of learning and teaching at KCMU College, where a path to sustainability is now being pursued. PMID:25072581

Comparison of three dimeric 18F-AlF-NOTA-RGD tracers.

PubMed

Guo, Jinxia; Lang, Lixin; Hu, Shuo; Guo, Ning; Zhu, Lei; Sun, Zhongchan; Ma, Ying; Kiesewetter, Dale O; Niu, Gang; Xie, Qingguo; Chen, Xiaoyuan

2014-04-01

RGD peptide-based radiotracers are well established as integrin αvβ3 imaging probes to evaluate tumor angiogenesis or tissue remodeling after ischemia or infarction. In order to optimize the labeling process and pharmacokinetics of the imaging probes, we synthesized three dimeric RGD peptides with or without PEGylation and performed in vivo screening. Radiolabeling was achieved through the reaction of F-18 aluminum-fluoride complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Three imaging probes were synthesized as (18)F-AlF-NOTA-E[c(RGDfK)]2, (18)F-AlF-NOTA-PEG4-E[c(RGDfK)]2, and (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2. The receptor binding affinity was determined by competitive cell binding assay, and the stability was evaluated by mouse serum incubation. Tumor uptake and whole body distribution of the three tracers were compared through direct tissue sampling and PET quantification of U87MG tumor-bearing mice. All three compounds remained intact after 120 min incubation with mouse serum. They all had a rapid and relatively high tracer uptake in U87MG tumors with good target-to-background ratios. Compared with the other two tracers, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 had the highest tumor uptake and the lowest accumulation in the liver. The integrin receptor specificity was confirmed by co-injection of unlabeled dimeric RGD peptide. The rapid one-step radiolabeling strategy by the complexation of (18)F-aluminum fluoride with NOTA-peptide conjugates was successfully applied to synthesize three dimeric RGD peptides. Among the three probes developed, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 with relatively low liver uptake and high tumor accumulation appears to be a promising candidate for further translational research.

In vivo fluorescence imaging of lysosomes: a potential technique to follow dye accumulation in the context of PDT?

NASA Astrophysics Data System (ADS)

Devoisselle, Jean-Marie; Mordon, Serge R.; Soulie-Begu, Sylvie

1995-03-01

Lysosomes and intracellular acidic compartments seem to play an important role in the context of PDT. Some photosensitizers are localized in the lysosomes of tumor-associated macrophages. Liposomes, which are lysosomotropic drug carriers, are used to deliver photosensitizers in tumors. Liposomes are taken up by the liver cells after intravenous injection. Intracellular pathway and liposomes localization in the different liver cells require sacrifice of the animals, cell separation, and observation by electronic microscopy. Little is known about liposomes kinetic uptake by the acidic intracellular compartments in vivo. We propose in this study a new method to follow liposomes uptake in the liver in vivo using a fluorescent pH-sensitive probe. We have already demonstrated the ability of fluorescence spectroscopy and imaging using a pH-dependent probe to monitor pH in living tissues. As pH of lysosome is very low, the kinetic of liposome uptake in this intracellular acidic compartment is followed by monitoring the pH of the whole liver in vivo and ex vivo. Liposomes-encapsulated carboxyfluorescein are prepared by the sonication procedure. Carboxyfluorescein is used at high concentration (100 mM) in order to quench its fluorescence. Liposomes are injected to Wistar rats into the peinil vein. After laparotomy, fluorescence spectra and images are recorded during two hours. Results show a rapid fluorescence increase followed by a slow phase of fluorescence decrease. pH decreases from physiological value to 6.0. After sacrifice and flush with cold saline solution, pH of liver ex vivo is found to be 5.0 - 5.5. These data show a rapid clearance of released dye and an uptake of liposomes by the liver cells and, as liposomes penetrate in the acidic compartment, dye is released from liposomes and is delivered in lysosomes leading to the decrease of pH.

A novel method for measuring cellular antibody uptake using imaging flow cytometry reveals distinct uptake rates for two different monoclonal antibodies targeting L1.

PubMed

Hazin, John; Moldenhauer, Gerhard; Altevogt, Peter; Brady, Nathan R

2015-08-01

Monoclonal antibodies (mAbs) have emerged as a promising tool for cancer therapy. Differing approaches utilize mAbs to either deliver a drug to the tumor cells or to modulate the host's immune system to mediate tumor kill. The rate by which a therapeutic antibody is being internalized by tumor cells is a decisive feature for choosing the appropriate treatment strategy. We herein present a novel method to effectively quantitate antibody uptake of tumor cells by using image-based flow cytometry, which combines image analysis with high throughput of sample numbers and sample size. The use of this method is established by determining uptake rate of an anti-EpCAM antibody (HEA125), from single cell measurements of plasma membrane versus internalized antibody, in conjunction with inhibitors of endocytosis. The method is then applied to two mAbs (L1-9.3, L1-OV52.24) targeting the neural cell adhesion molecule L1 (L1CAM) at two different epitopes. Based on median cell population responses, we find that mAb L1-OV52.24 is rapidly internalized by the ovarian carcinoma cell line SKOV3ip while L1 mAb 9.3 is mainly retained at the cell surface. These findings suggest the L1 mAb OV52.24 as a candidate to be further developed for drug-delivery to cancer cells, while L1-9.3 may be optimized to tag the tumor cells and stimulate immunogenic cancer cell killing. Furthermore, when analyzing cell-to-cell variability, we observed L1 mAb OV52.24 rapidly transition into a subpopulation with high-internalization capacity. In summary, this novel high-content method for measuring antibody internalization rate provides a high level of accuracy and sensitivity for cell population measurements and reveals further biologically relevant information when taking into account cellular heterogeneity. Copyright © 2015 Elsevier B.V. All rights reserved.

An evaluation of the phosphorus storage capacity of an anaerobic/aerobic sequential batch biofilm reactor.

PubMed

Chiou, Ren-Jie; Yang, Yi-Rong

2008-07-01

The aim of this work was to assess the phosphorus storage capability of the polyphosphate (poly-P) accumulating organisms (PAO) in the biofilm using a sequential batch biofilm reactor (SBBR). In the anaerobic phase, the specific COD uptake rates increases from 0.05 to 0.22 (mg-COD/mg-biomass/h) as the initial COD increases and the main COD uptake activity occurs in the initial 30 min. The polyhydroxyalkanoates (PHAs) accumulation from 18 to 38 (mg-PHA/g-biomass) and phosphorus release from 20 to 60 (mg-P/L) share a similar trend. The adsorbed COD cannot be immediately transformed to PHAs. Since the PHAs' demand per released phosphorus is independent of the initial COD, the enhancement of the PHA accumulation would be of benefit to phosphorus release. The only requirement is to have an initial amount of substrate that will result in sufficient PHA accumulation (approximately 20 mg-PHA/g-biomass) for phosphorus release. During the aerobic phase, the aeration should not only provide sufficient dissolved oxygen, but should also enhance the mass transfer and the diffusion. In other words, the limitation to the phosphorus storage capability always occurs during the anaerobic phase, not the aerobic phase.

A rapid and efficient method to study the function of crop plant transporters in Arabidopsis

USDA-ARS?s Scientific Manuscript database

Iron (Fe) is an essential micronutrient for humans. Fe deficiency disease is wide-spread and has lead to extensive studies on the mechanisms of Fe uptake and storage, especially in staple food crops such as rice. However, studies of functionally related genes in rice and other crops are often time a...

Integrating soil and weather information into canopy sensor algorithms for improved corn nitrogen rate recommendation

USDA-ARS?s Scientific Manuscript database

Corn production can be often limited by the loss of nitrogen (N) due to leaching, volatilization and denitrification. The use of canopy sensors for making in-season N fertilizer applications has been proven effective in matching plant N requirements with periods of rapid N uptake (V7-V11), reducing ...

E-Learning in Australia and Korea: Learning from Practice

ERIC Educational Resources Information Center

Misko, Josie; Choi, Jihee; Hong, Sun Yee; Lee, In Sook

2004-01-01

This project investigates the uptake of e-learning in two countries (Australia and Korea) which have experienced a rapid expansion of the use of information technology in education and training. A key finding is that although e-learning can increase flexibility and cost efficiencies in the delivery of training, it cannot on its own guarantee…

Transformations in the Field of Symbolic Control and Their Implications for the Greek Educational Administration

ERIC Educational Resources Information Center

Tsatsaroni, Anna; Sifakakis, Polychronis; Sarakinioti, Antigone

2015-01-01

This paper theorises the field of symbolic control and reflects on the critical literature of policy studies, exploring the possibilities that the former might offer to the analysis of global policy discourses and their up-take in specific national and local contexts. Starting from the rapidly expanding literature on the "globalising"…

Post-harvest soil nitrate following corn production in eight Midwestern states

USDA-ARS?s Scientific Manuscript database

Applying nitrogen (N) at economically optimal rates (EONR) and at times of rapid crop uptake are practices that are thought to minimize the amount of residual soil nitrate (RSN) in the profile that may be susceptible to loss. The objective of this study was to evaluate the effects of rate (0 to 314 ...

Confocal analysis of hepatocellular long-chain fatty acid uptake.

PubMed

Elsing, C; Winn-Börner, U; Stremmel, W

1995-12-01

Transmembrane transport and cytosolic accumulation of fatty acids were investigated using confocal laser scanning microscopy (cLSM). A Zeiss LSM 310 system was used to determine the uptake of the fluorescent fatty acid derivative 12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3- diazol-4-yl)amino]octadecanoic acid (12-NBD stearate) (C18) in single rat hepatocytes. Uptake was a saturable process with a Michaelis-Menten constant value of 68 nM. Initial uptake velocity was dependent on extracellular presence of albumin and beta-lactoglobulin. Absence of albumin reduced uptake to 32 +/- 16% (P < 0.01) of control values. In the presence of unlabeled stearate, uptake of 12-NBD stearate was lowered to 49 +/- 12% (P < 0.01). Ion substitution experiments showed no sodium dependency of uptake. Increase in membrane potential led to a pronounced accumulation of the fatty acid derivative within the plasma membrane and in the adjacent cytoplasmic compartment, whereas membrane depolarization had no effect on uptake rates. In separate experiments line scans through representative hepatocytes were analyzed to generate "x-t" plots. 12-NBD stearate showed a fluorescence pattern with prominent staining of the area of the plasma membrane and the adjacent cytoplasm, dependent on the presence of extracellular albumin. For the hepatocellular cytosolic accumulation process of 12-NBD stearate a diffusion constant of 22.2 +/- 6.2 x 10(-9) cm2/s was calculated. In contrast to the long-chain fatty acid derivative 12-NBD stearate, short (C5)- and medium (C11)-chain fatty acids revealed no membrane interaction with hepatocytes. Erythrocytes also lacked a membrane interaction process for 12-NBD stearate. In conclusion, it was demonstrated that cLSM is capable of directly evaluating the cellular fatty acid uptake process at a subcellular level.

Cutoff value of thyroid uptake of (99m)Tc-pertechnetate to discriminate between Graves' disease and painless thyroiditis: a single center retrospective study.

PubMed

Uchida, Toyoyoshi; Suzuki, Ruriko; Kasai, Takatoshi; Onose, Hiroyuki; Komiya, Koji; Goto, Hiromasa; Takeno, Kageumi; Ishii, Shinya; Sato, Junko; Honda, Akira; Kawano, Yui; Himuro, Miwa; Yamada, Emiko; Yamada, Tetsu; Watada, Hirotaka

2016-01-01

Thyroid uptake of (99m)Tc-pertechnetate is a useful way to determine the cause of thyrotoxicosis. In daily clinical practice, (99m)Tc-pertechnetate uptake is used to discriminate between Graves' disease and painless thyroiditis when clinical information is not enough to make the distinction. However, since the optimal cutoff value of (99m)Tc-pertechnetate uptake has not yet been elucidated, our aim was to determine this value. We recruited patients with thyrotoxicosis in whom (99m)Tc-pertechnetate uptake was measured in clinical settings between 2009 and 2013. Three experienced endocrinologists (who were blinded to the value of (99m)Tc-pertechnetate uptake and initial treatment) diagnosed the cause of thyrotoxicosis based on thyrotropin, free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels, and by ultrasound findings and using images of thyroid uptake of (99m)Tc-pertechnetate without the actual values. Ninety-four patients diagnosed as having Graves' disease or painless thyroiditis were finally included. According to the diagnosis, the optimal cutoff value of (99m)Tc-pertechnetate uptake was determined by receiver operating characteristics analysis. A cutoff value of 1.0% provided optimal sensitivity and specificity of 96.6% and 97.1%, respectively. Then, its validity was confirmed in 78 patients with confirmed Graves' disease or painless thyroiditis diagnosed at another institute. Applying this cutoff value to the patients with thyrotoxicosis revealed positive and negative predictive values for Graves' disease of 100% and 88.9%, respectively. In conclusion, a cutoff value for (99m)Tc-pertechnetate uptake of 1.0% was useful to discriminate between Graves' disease and painless thyroiditis.

Proton-coupled organic cation antiporter-mediated uptake of apomorphine enantiomers in human brain capillary endothelial cell line hCMEC/D3.

PubMed

Okura, Takashi; Higuchi, Kei; Kitamura, Atsushi; Deguchi, Yoshiharu

2014-01-01

R(-)-Apomorphine is a dopamine agonist used for rescue management of motor function impairment associated with levodopa therapy in Parkinson's disease patients. The aim of this study was to examine the role of proton-coupled organic cation antiporter in uptake of R(-)-apomorphine and its S-enantiomer in human brain, using human endothelial cell line hCMEC/D3 as a model. Uptake of R(-)- or S(+)-apomorphine into hCMEC/D3 cells was measured under various conditions to evaluate its time-, concentration-, energy- and ion-dependency. Inhibition by selected organic cations was also examined. Uptakes of both R(-)- and S(+)-apomorphine increased with time. The initial uptake velocities of R(-)- and S(+)-apomorphine were concentration-dependent, with similar Km and Vmax values. The cell-to-medium (C/M) ratio of R(-)-apomorphine was significantly reduced by pretreatment with sodium azide, but was not affected by replacement of extracellular sodium ion with N-methylglucamine or potassium. Intracellular alkalization markedly reduced the uptake, while intracellular acidification increased it, suggesting that the uptake is driven by an oppositely directed proton gradient. The C/M ratio was significantly decreased by amantadine, verapamil, pyrilamine and diphenhydramine (substrates or inhibitors of proton-coupled organic cation antiporter), while tetraethylammonium (substrate of organic cation transporters (OCTs)) and carnitine (substrate of carnitine/organic cation transporter 2; (OCTN2)) had no effect. R(-)-Apomorphine uptake was competitively inhibited by diphenhydramine. Our results indicate that R(-)-apomorphine transport in human blood-brain barrier (BBB) model cells is similar to S(+)-apomorphine uptake. The transport was dependent on an oppositely directed proton gradient, but was sodium- or membrane potential-independent. The transport characteristics were consistent with involvement of the previously reported proton-coupled organic cation antiporter.

Acute toxicity and accumulation of the piscicide 3-trifluoromethyl-4- nitrophenol (TFM) in freshwater mussels (Bivalvia: Unionidae)

USGS Publications Warehouse

Waller, D.L.; Rach, J.J.; Luoma, J.A.

1998-01-01

We compared the acute toxicity and initial accumulation of the piscicide TFM (3-trifluoromethyl-4-nitrophenol) in the freshwater unionacean mussels, Obliquaria reflexa and Fusconaia flava. Acute 48 h toxicity tests were conducted to determine the LC50 values for each species. The initial uptake clearances of TFM were measured by exposing the mussels to [14C]-TFM and counting the radioactivity in four organ tissues (foot, gill, mantle and viscera) over 48 h. TFM was about 2-fold more toxic to O. reflexa (LC50 1.80 mg I-1) than to F. flava (LC50 3.81 mg L-1) and the difference was not explained by accumulation patterns. The initial uptake clearance rates (0-6 h) for the whole body were similar between the species (11.2 ml g-1 h-2 in O. reflexa and 9.5 ml g-1 h-1 in F. flava). The accumulation of TFM residues among the organ tissues was also similar between species. The uptake clearance rates (ml g-1 h-1) of TFM equivalents were generally highest in the gill, but not significantly different than other organ tissues. The normalized concentration of TFM residues (??g per g whole body) was highest in the viscera. The toxicity data suggest that the mortality of both species would be minimal from sea lamprey control treatments with TFM. However, the behavioural effects and accumulation rates also indicate that mussels do not effectively avoid TFM exposure by valve closure.

Kinetic evaluation of chromium(VI) sorption by water lettuce (Pistia).

PubMed

Chakraborty, Rupa; Karmakar, Sukalpa; Mukherjee, Somnath; Kumar, Sunil

2014-01-01

An investigation was performed to evaluate the uptake capacity of Pistia in living condition for adsorptive removal of chromium(VI) from spiked solution for examining a remedial measure for disposal of chrome-laden wastewater in an urban wetland system. Kinetics results show about 78% removal was achieved for 3 mg/L initial concentration of Cr(VI). Experimental data showed that the root portion absorbed more Cr(VI) (28.54 μg/g) compared to accumulation in leaf (5.73 μg/g). It was also noted that the plant could effectively remove Cr(VI) from the solution with minor damage up to an initial Cr(VI) concentration of 3 mg/L, for which the adsorption isotherm studies were conducted. The maximum uptake capacity of the plant was recorded as 0.05 mg/g of Cr(VI) at the equilibrium level after a contact period of 7 days for an initial concentration of 8 mg /L, although severe physiological damage occurred. The experimental results were plotted in Langmuir and Freundlich isotherm models and both were found to be well fitted (r(2) = 0.979 and r(2) = 0.974 respectively). The high value of n (2.16) reveals a strong bond between the plant root and dissolved Cr(VI), which favours the adsorption process. The order of the reaction was also examined on the basis of uptake capacity and it was found that the second order model fitted best.

Nanomedicine strategies for sustained, controlled, and targeted treatment of cancer stem cells of the digestive system.

PubMed

Xie, Fang-Yuan; Xu, Wei-Heng; Yin, Chuan; Zhang, Guo-Qing; Zhong, Yan-Qiang; Gao, Jie

2016-10-15

Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

Binding of Dissolved Strontium by Micrococcus luteus

PubMed Central

Faison, Brendlyn D.; Cancel, Carmen A.; Lewis, Susan N.; Adler, Howard I.

1990-01-01

Resting cells of Micrococcus luteus have been shown to remove strontium (Sr) from dilute aqueous solutions of SrCl2 at pH 7. Loadings of 25 mg of Sr per g of cell dry weight were achieved by cells exposed to a solution containing 50 ppm (mg/liter) of Sr. Sr binding occurred in the absence of nutrients and did not require metabolic activity. Initial binding was quite rapid (<0.5 h), although a slow, spontaneous release of Sr was observed over time. Sr binding was inhibited in the presence of polyvalent cations but not monovalent cations. Ca and Sr were bound preferentially over all other cations tested. Sr-binding activity was localized on the cell envelope and was sensitive to various chemical and physical pretreatments. Bound Sr was displaced by divalent ions or by H+. Other monovalent ions were less effective. Bound Sr was also removed by various chelating agents. It was concluded that Sr binding by M. luteus is a reversible equilibrium process. Both ion exchange mediated by acidic cell surface components and intracellular uptake may be involved in this activity. PMID:16348370

Succeeding in New Vaccine Introduction: Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Cameroon, Kenya, and Nigeria

PubMed Central

Snidal, Sarah; Saidu, Yauba; Ojumu, Abiola; Ngatia, Antony; Bagana, Murtala; Mutuku, Faith; Sobngwi, Joelle; Efe-Aluta, Oniovo; Roper, Julia; LeTallec, Yann; Kang’ethe, Alice

2017-01-01

Abstract Introducing a new vaccine is a large-scale endeavor that can face many challenges, resulting in introduction delays and inefficiencies. The development of national task teams and tools, such as prelaunch trackers, for the introduction of new vaccines (hereafter, “new vaccine introductions” [NVIs]) can help countries implement robust project management systems, front-load critical preparatory activities, and ensure continuous communication around vaccine supply and financing. In addition, implementing postlaunch assessments to take rapid corrective action accelerates the uptake of the new vaccines. NVIs can provide an opportunity to strengthen routine immunization, through strengthening program management systems or by reinforcing local immunization managers’ abilities, among others. This article highlights key lessons learned during the introduction of inactivated poliovirus vaccine in 3 countries that would make future NVIs more successful. The article concludes by considering how the Immunization Systems Management Group of the Global Polio Eradication Initiative has been useful to the NVI process and how such global structures could be further enhanced. PMID:28838156

Methylmercury Uptake and Degradation by Methanotrophs

DOE PAGES

Lu, Xia; Gu, Wenyu; Zhao, Linduo; ...

2017-05-31

Methylmercury (CH 3Hg +) is a potent neurotoxin produced by certain anaerobic microorganisms in natural environments. While numerous studies have characterized the basis of mercury methylation, no studies have examined CH 3Hg + degradation by methanotrophs, despite their ubiquitous presence in the environment. We report that some methanotrophs (e.g., Methylosinus trichosporium OB3b) can take up and degrade CH 3Hg + rapidly, whereas others (e.g., Methylococcus capsulatus Bath) can take up but not degrade CH 3Hg +. Demethylation by M. trichosporium OB3b increases with increasing CH 3Hg + concentrations but is abolished in mutants deficient in methanobactin biosynthesis. Further, addition ofmore » methanol as a competing C1 substrate inhibits demethylation, suggesting that CH3Hg+ degradation by methanotrophs may involve an initial bonding of CH 3Hg + by methanobactin followed by cleavage of the C-Hg bond in CH 3Hg + by the methanol dehydrogenase. This new demethylation pathway by methanotrophs indicates possible broader involvement of C1-metabolizing aerobes in the environmental degradation of toxic CH3Hg+.« less

Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease.

PubMed

Bandara, Nilantha; Sharma, Anuj K; Krieger, Stephanie; Schultz, Jason W; Han, Byung Hee; Rogers, Buck E; Mirica, Liviu M

2017-09-13

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11 C (20.4 min) and 18 F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64 Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described herein are a series of bifunctional chelators (BFCs), L 1 -L 5 , that were designed to tightly bind 64 Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD.

Testosterone-secreting adrenal adenoma in a peripubertal girl

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

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.

1987-11-13

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started fourmore » months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.« less

Nanomedicine strategies for sustained, controlled, and targeted treatment of cancer stem cells of the digestive system

PubMed Central

Xie, Fang-Yuan; Xu, Wei-Heng; Yin, Chuan; Zhang, Guo-Qing; Zhong, Yan-Qiang; Gao, Jie

2016-01-01

Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system. PMID:27795813

Oxidation Kinetics of Cast TiAl3

NASA Technical Reports Server (NTRS)

Smialek, J. L.; Humphrey, D. L.

1992-01-01

The isothermal oxidation kinetics of the TiAl3 compound over a wide temperature range is documented, and these rates are related to exclusive alpha-Al2O3 scale growth. The specific weight change vs time curves are shown. Two abnormalities are immediately apparent. One is that a rapid initial uptake of oxygen occurs at times less than 5 h, followed by a lower oxidation rate at longer times, for tests at 900 C and below. The other is that the final weight changes for the 700, 800, and 900 C tests are not in the sequence expected with respect to temperature. Isothermal oxidation of drop cast TiAl above 1000 C was found to exhibit parabolic oxidation controlled by protective alpha-Al2O3 scale formation. TiAl is the only phase in the binary Ti-Al system that forms exclusive scales of alpha-Al2O3 in isothermal oxidation. High anomalous rates at short times and at temperatures below 1000 C resulted from the internal oxidation of a second phase of aluminum.

Methylmercury Uptake and Degradation by Methanotrophs

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

Lu, Xia; Gu, Wenyu; Zhao, Linduo

Methylmercury (CH 3Hg +) is a potent neurotoxin produced by certain anaerobic microorganisms in natural environments. While numerous studies have characterized the basis of mercury methylation, no studies have examined CH 3Hg + degradation by methanotrophs, despite their ubiquitous presence in the environment. We report that some methanotrophs (e.g., Methylosinus trichosporium OB3b) can take up and degrade CH 3Hg + rapidly, whereas others (e.g., Methylococcus capsulatus Bath) can take up but not degrade CH 3Hg +. Demethylation by M. trichosporium OB3b increases with increasing CH 3Hg + concentrations but is abolished in mutants deficient in methanobactin biosynthesis. Further, addition ofmore » methanol as a competing C1 substrate inhibits demethylation, suggesting that CH3Hg+ degradation by methanotrophs may involve an initial bonding of CH 3Hg + by methanobactin followed by cleavage of the C-Hg bond in CH 3Hg + by the methanol dehydrogenase. This new demethylation pathway by methanotrophs indicates possible broader involvement of C1-metabolizing aerobes in the environmental degradation of toxic CH3Hg+.« less

Perceived Utility of the RE-AIM Framework for Health Promotion/Disease Prevention Initiatives for Older Adults: A Case Study from the U.S. Evidence-Based Disease Prevention Initiative

PubMed Central

Ory, Marcia G.; Altpeter, Mary; Belza, Basia; Helduser, Janet; Zhang, Chen; Smith, Matthew Lee

2015-01-01

Dissemination and implementation (D&I) frameworks are increasingly being promoted in public health research. However, less is known about their uptake in the field, especially for diverse sets of programs. Limited questionnaires exist to assess the ways that frameworks can be utilized in program planning and evaluation. We present a case study from the United States that describes the implementation of the RE-AIM framework by state aging services providers and public health partners and a questionnaire that can be used to assess the utility of such frameworks in practice. An online questionnaire was developed to capture community perspectives about the utility of the RE-AIM framework. Distributed to project leads in 27 funded states in an evidence-based disease prevention initiative for older adults, 40 key stakeholders responded representing a 100% state-participation rate among the 27 funded states. Findings suggest that there is perceived utility in using the RE-AIM framework when evaluating grand-scale initiatives for older adults. The RE-AIM framework was seen as useful for planning, implementation, and evaluation with relevance for evaluators, providers, community leaders, and policy makers. Yet, the uptake was not universal, and some respondents reported difficulties in use, especially adopting the framework as a whole. This questionnaire can serve as the basis to assess ways the RE-AIM framework can be utilized by practitioners in state-wide D&I efforts. Maximal benefit can be derived from examining the assessment of RE-AIM-related knowledge and confidence as part of a continual quality assurance process. We recommend such an assessment be performed before the implementation of new funding initiatives and throughout their course to assess RE-AIM uptake and to identify areas for technical assistance. PMID:25964897

Inhibition of Phosphate Uptake in Corn Roots by Aluminum-Fluoride Complexes1

PubMed Central

Façanha, Arnoldo Rocha; Okorokova-Façanha, Anna L.

2002-01-01

F forms stable complexes with Al at conditions found in the soil. Fluoroaluminate complexes (AlFx) have been widely described as effective analogs of inorganic phosphate (Pi) in Pi-binding sites of several proteins. In this work, we explored the possibility that the phytotoxicity of AlFx reflects their activity as Pi analogs. For this purpose, 32P-labeled phosphate uptake by excised roots and plasma membrane H+-ATPase activity were investigated in an Al-tolerant variety of maize (Zea mays L. var. dwarf hybrid), either treated or not with AlFx. In vitro, AlFx competitively inhibited the rate of root phosphate uptake as well as the H+-ATPase activity. Conversely, pretreatment of seedlings with AlFx in vivo promoted no effect on the H+-ATPase activity, whereas a biphasic effect on Pi uptake by roots was observed. Although the initial rate of phosphate uptake by roots was inhibited by AlFx pretreatment, this situation changed over the following minutes as the rate of uptake increased and a pronounced stimulation in subsequent 32Pi uptake was observed. This kinetic behavior suggests a reversible and competitive inhibition of the phosphate transporter by fluoroaluminates. The stimulation of root 32Pi uptake induced by AlFx pretreatment was tentatively interpreted as a phosphate starvation response. This report places AlF3 and AlF4− among Al-phytotoxic species and suggests a mechanism of action where the accumulation of Pi-mimicking fluoroaluminates in the soil may affect the phosphate absorption by plants. The biochemical, physiological, and environmental significance of these findings is discussed. PMID:12177489

Inspecting the Mechanism: A Longitudinal Analysis of Socioeconomic Status Differences in Perceived Influenza Risks, Vaccination Intentions, and Vaccination Behaviors during the 2009-2010 Influenza Pandemic.

PubMed

Maurer, Jürgen

2016-10-01

Influenza vaccination is strongly associated with socioeconomic status, but there is only limited evidence on the respective roles of socioeconomic differences in vaccination intentions versus corresponding differences in follow-through on initial vaccination plans for subsequent socioeconomic differences in vaccine uptake. Nonparametric mean smoothing, linear regression, and probit models were used to analyze longitudinal survey data on perceived influenza risks, behavioral vaccination intentions, and vaccination behavior of adults during the 2009-2010 influenza A/H1N1 ("swine flu") pandemic in the United States. Perceived influenza risks and behavioral vaccination intentions were elicited prior to the availability of H1N1 vaccine using a probability scale question format. H1N1 vaccine uptake was assessed at the end of the pandemic. Education, income, and health insurance coverage displayed positive associations with behavioral intentions to get vaccinated for pandemic influenza while employment was negatively associated with stated H1N1 vaccination intentions. Education and health insurance coverage also displayed significant positive associations with pandemic vaccine uptake. Moreover, behavioral vaccination intentions showed a strong and statistically significant positive partial association with later H1N1 vaccination. Incorporating vaccination intentions in a statistical model for H1N1 vaccine uptake further highlighted higher levels of follow-through on initial vaccination plans among persons with higher education levels and health insurance. Sampling bias, misreporting in self-reported data, and limited generalizability to nonpandemic influenza are potential limitations of the analysis. Closing the socioeconomic gap in influenza vaccination requires multipronged strategies that not only increase vaccination intentions by improving knowledge, attitudes, and beliefs but also facilitate follow-through on initial vaccination plans by improving behavioral control and access to vaccination for individuals with low education, employed persons, and the uninsured. © The Author(s) 2015.

A prescription for health: a primary care based intervention to maintain the non-smoking status of young people

PubMed Central

Fidler, W.; Lambert, T.

2001-01-01

OBJECTIVES—To evaluate the effectiveness of primary health care teams in maintaining a group of young people aged 10-15 years as non-smokers.
DESIGN—Randomised controlled trial using postal questionnaires.
SETTING—Oxfordshire, UK.
SUBJECTS—2942 young people who were initially self declared non-smokers.
INTERVENTION—Information about smoking, sent under signature of the subject's general practitioner, certificates and posters intended to reinforce non-smoking behaviour.
MAIN OUTCOME MEASURES—Changes in smoking behaviour, attitudes measured after one year.
RESULTS—After a year, smoking uptake was 7.8% in the control group compared with 5.1% in the intervention group (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1 to 2.2). Among boys the corresponding results were 5.2% and 2.4% (OR 2.3, 95% CI 1.2 to 4.6), and among girls 10.0% and 7.5% (OR 1.4, 95% CI 0.9 to 2.1). Among boys aged 14-15 the uptake rate was 12.8% in the control group compared with 5.4% in the intervention group. However, among girls of the same age the intervention was less effective, with smoking uptake of 15.1% in the control group and 12.8% in the intervention group. The intervention was more effective among young people whose initial attitudes identified them as definite non-smokers than those who were potential smokers.
CONCLUSIONS—The intervention substantially reduced smoking uptake among the young people, particularly boys. Primary health care teams can play an important role in maintaining the non-smoking status of their young patients. Confidential postal contact from the doctor direct to the young person at home is influential and cost-effective.


Keywords: smoking initiation; smoking prevention; young people; primary care PMID:11226356

Inspecting the Mechanism: A Longitudinal Analysis of Socioeconomic Status Differences in Perceived Influenza Risks, Vaccination Intentions and Vaccination Behaviors during the 2009-2010 Influenza Pandemic

PubMed Central

Maurer, Jürgen

2015-01-01

Background Influenza vaccination is strongly associated with socioeconomic status, but there is only limited evidence on the respective roles of socioeconomic differences in vaccination intentions vs. corresponding differences in follow through on initial vaccination plans for subsequent socioeconomic differences in vaccine uptake. Methods Nonparametric mean smoothing, linear regression and Probit models were used to analyze longitudinal survey data on perceived influenza risks, behavioral vaccination intentions and vaccination behavior of adults during the 2009-10 influenza A/H1N1 (“Swine Flu”) pandemic in the United States. Perceived influenza risks and behavioral vaccination intentions were elicited prior to the availability of H1N1 vaccine using a probability scale question format. H1N1 vaccine uptake was assessed at the end of the pandemic. Results Education, income and health insurance coverage displayed positive associations with behavioral intentions to get vaccinated for pandemic influenza while employment was negatively associated with stated H1N1 vaccination intentions. Education and health insurance coverage also displayed significant positive associations with pandemic vaccine uptake. Moreover, behavioral vaccination intentions showed a strong and statistically significant positive partial association with later H1N1 vaccination. Incorporating vaccination intentions in a statistical model for H1N1 vaccine uptake further highlighted higher levels of follow through on initial vaccination plans among persons with higher education levels and health insurance. Limitations Sampling bias, misreporting in self-reported data, and limited generalizability to non-pandemic influenza are potential limitations of the analysis. Conclusions Closing the socioeconomic gap in influenza vaccination requires multi-pronged strategies that not only increase vaccination intentions by improving knowledge, attitudes and beliefs but also facilitate follow through on initial vaccination plans by improving behavioral control and access to vaccination for individuals with low education, employed persons and the uninsured. PMID:26416814