Affinity Uptake Research Articles

Allometric scaling and taxonomic variation in nutrient utilization traits and maximum growth rate of phytoplankton

Nutrient utilization traits can be used to link the ecophysiology of phytoplankton to population dynamic models and the structure of communities across environmental gradients. Here we analyze a comprehensive literature compilation of four traits: maximum nutrient uptake rate; the half‐saturation constant for nutrient uptake; the minimum subsistence quota, measured for nitrate and phosphate; and maximum growth rate. We also use these traits to analyze two composite traits, uptake affinity and scaled uptake affinity. All traits tend to increase with cell volume, except for scaled uptake affinity and maximum growth rate, which tend to decline with cell volume. Most scaling relationships are the same for freshwater and marine species, although important differences exist. Most traits differ on average between major taxa, but between‐taxon variation is nearly always due to between‐taxon variation in volume. There is some evidence for between‐trait correlations that could constrain trait evolution, but these correlations are difficult to disentangle from correlation driven by cell volume. These results should enhance the parameterization of models that use size or taxonomic group to structure physiological variation in phytoplankton communities.

Study on Enhancement Adsorption of Pipemidic Acid from Aqueous Solution by Using an Amino Group Modified Hypercrosslinked Polymeric Adsorbents

In the present study, an amino group modified hypercrosslinked polymeric adsorbent RDM-200 was prepared and its ability to adsorb pipemidic acid from aqueous solution was tested by using Amberlite XAD-4 as a comparison. Pipemidic acid adsorption isotherm onto RDM-200 is well described by the Freundlich model. The RDM-200 adsorption capacity for PPA was about 510.5 mg/g at 293 K, exhibited larger uptake and stronger affinity of pipemidic acid than XAD-4. The adsorption thermodynamic parameters were calculated and the adsorption was an exothermic, favorable, and more ordered process. The RDM-200 spontaneously adsorbs pipemidic acid mainly by both entropy change and enthalpy change. The RDM-200 exhibited excellent adsorption ability over the pH range 6-10, NaCl showed the positive effect.

Uptake and transport of nitrogen derived from sessile epifauna in the giant kelp Macrocystis pyrifera

Sessile epifauna that excrete ammonium as a waste product are often closely associated with surfaces of macroalgae that are able to absorb and use ammonium for growth. This close association means that nitrogen provisioning from epifauna to host macroalgae is probable, but barriers to uptake, formed by epifaunal colonies, and the physiological status of colonised macroalgal tissue may limit the amount of ammonium absorbed by colonised macroalgae. Evidence for the movement of nitrogen from sessile epifauna into and around the giant kelp Macrocystis pyrifera was gathered using a 15N-enriched stable isotope tracer. Experiments in which 15N-labelled phytoplankton was fed to the epifaunal bryozoan Membranipora membranacea did not to find conclusive evidence for the flow of nitrogen released by bryozoan colonies into colonised M. pyrifera tissue. The low degree of transmission of 15N observed may be due to the barrier to nitrogen uptake that is formed by M. membranacea tissue and the low affinity for ammonium uptake by M. pyrifera blades during winter. M. membranacea is unlikely to provide significant benefits to host macroalgae via nitrogen provision in many situations, due to its sheet-forming habit and its absence during summer low-nitrogen periods. In situ incubations of M. pyrifera blades in 15N-enriched ammonium were used to determine if ammonium provided by epifaunal colonies could be taken up by mature blades tissue and exported to the stipe for long-distance transport to actively growing meristems. Uptake and export of labelled nitrogen from basal blades into the stipe was measured, and the potential for longdistance transport of nitrogen from older blades was confirmed. Active transport of nitrogen from older macro algal tissue colonised by epifauna such as hydroids could be an important mechanism allowing kelp with specialised long-distance solute transport systems to tolerate nitrogen limitation.

Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells

The activity of a peptide nucleic acid (PNA) targeting cancer-associated microRNA-221 is described. PNAs against miR-221 were designed in order to bind very efficiently to the target RNA strand and to undergo efficient uptake in the cells. A polyarginine-PNA conjugate targeted against miR-221 (Rpep-PNA-a221) showed both very high affinity for RNA and efficient cellular uptake without the addition of transfection reagents. Unmodified PNA with the same sequence displayed RNA binding, but cellular uptake was very poor. Consistently, only Rpep-PNA-a221 strongly inhibited miR-221. Targeting miR-221 by PNA resulted in i) lowering of the hybridization levels of miR-221 measured by RT-qPCR, ii) upregulation of p27Kip1 gene expression, measured by RT-qPCR and western blot analysis. The major conclusion of this study is that efficient delivery of anti‑miR PNA through a suitable peptide carrier (Rpep‑PNA-a221) leads to inhibition of miR-221 activity, altering the expression of miR-221-regulated functions in breast cancer cells.

18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic β-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic β-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared (18)F radioligands for GLP-1R by the reaction of [(18)F]FBEM, a maleimide prosthetic group, with [Cys(0)] and [Cys(40)] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [(18)F]FBEM-[Cys(x)]-exendin-4 analogs were obtained in good yield (34.3 ± 3.4%, n = 11), based on the starting compound [(18)F]FBEM), and had a specific activity of 45.51 ± 16.28 GBq/μmol (1.23 ± 0.44 Ci/μmol, n = 7) at the end of synthesis. The C-terminal isomer, [(18)F]FBEM-[Cys(40)]-exendin-4, had higher affinity for INS-1 tumor cells (IC(50) 1.11 ± 0.057 nM) and higher tumor uptake (25.25 ± 3.39 %ID/g at 1 h) than the N-terminal isomer, [(18)F]FBEM-[Cys(0)]-exendin-4 (IC(50) 2.99 ± 0.06 nM, uptake 7.20 ± 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys(x)]-exendin-4 (p < 0.05). [(18)F]FBEM-[Cys(40)]-exendin-4 and [(18)F]FBEM-[Cys(0)]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors exhibited by [(18)F]FBEM-[Cys(40)]-exendin-4 suggests that this compound would be the better tracer for imaging GLP-1R.

Independent colimitation for carbon dioxide and inorganic phosphorus.

Simultaneous limitation of plant growth by two or more nutrients is increasingly acknowledged as a common phenomenon in nature, but its cellular mechanisms are far from understood. We investigated the uptake kinetics of CO2 and phosphorus of the algae Chlamydomonas acidophila in response to growth at limiting conditions of CO2 and phosphorus. In addition, we fitted the data to four different Monod-type models: one assuming Liebigs Law of the minimum, one assuming that the affinity for the uptake of one nutrient is not influenced by the supply of the other (independent colimitation) and two where the uptake affinity for one nutrient depends on the supply of the other (dependent colimitation). In addition we asked whether the physiological response under colimitation differs from that under single nutrient limitation.We found no negative correlation between the affinities for uptake of the two nutrients, thereby rejecting a dependent colimitation. Kinetic data were supported by a better model fit assuming independent uptake of colimiting nutrients than when assuming Liebigs Law of the minimum or a dependent colimitation. Results show that cell nutrient homeostasis regulated nutrient acquisition which resulted in a trade-off in the maximum uptake rates of CO2 and phosphorus, possibly driven by space limitation on the cell membrane for porters for the different nutrients. Hence, the response to colimitation deviated from that to a single nutrient limitation. In conclusion, responses to single nutrient limitation cannot be extrapolated to situations where multiple nutrients are limiting, which calls for colimitation experiments and models to properly predict growth responses to a changing natural environment. These deviations from single nutrient limitation response under colimiting conditions and independent colimitation may also hold for other nutrients in algae and in higher plants.

99mTcI/ReI Tricarbonyl Complexes with Tridentate Cysteamine Based Ligands: Synthesis, Characterization and in vitro/in vivo Evaluation

AbstractTricarbonyl MI (M = Re, 99mTc) complexes of a new tridentate cysteamine based chelator have been synthesized and fully characterized. To gain an insight into the usefulness of this new chelator for labeling biomolecules with a fac‐[M(CO)3]+ core, the ligand framework has been functionalized with a N‐(dialkylaminoalkyl) pharmacophore. The corresponding 99mTcI complexes showed moderate affinity for melanin and moderate cell uptake by B16F1 murine melanoma cells, and therefore deserve further evaluation in vivo as radioactive probes for the detection of melanomas.

Modulation of the Biological Activity of microRNA‐210 with Peptide Nucleic Acids (PNAs)

Herein we describe the activity of a peptide nucleic acid (PNA) that targets microRNA-210 (miR-210), which is associated with hypoxia and is modulated during erythroid differentiation. PNAs directed against miR-210 were designed to bind with high affinity to the target RNA strand and to undergo efficient uptake in target cells. A polyarginine-PNA conjugate directed against miR-210 (Rpep-PNA-a210) showed both very high affinity for RNA and efficient uptake into target cells without the need for transfection reagents. An unmodified PNA of the same sequence displayed the ability to bind RNA, but cellular uptake was very poor. Consistent with this, only Rpep-PNA-a210 strongly inhibited miR-210 activity, as evaluated by assays on undifferentiated K562 cells and on cells treated with mithramycin, which was found to induce erythroid differentiation and miR-210 overexpression. Targeting miR-210 by Rpep-PNA-a210 resulted in: 1) a decrease in miR-210 levels as measured by RT-PCR, 2) up-regulation of raptor mRNA, 3) a decrease in γ-globin mRNA, and 4) decreased expression of differentiated functions (i.e., proportion of benzidine-positive cells, content of embryo-fetal hemoglobins). The efficient delivery of anti-miR PNAs through a suitable peptide carrier (Rpep-PNA-a210) leads to the inhibition of miR-210 activity, altering the expression of miR-210-regulated erythroid functions.

Nutrient uptake and growth responses of three intertidal macroalgae with perennial, opportunistic and summer-annual strategies

An important life history trait of macroalgae species is the physiological ability to cope with nutrient limiting conditions, which seasonally occur in temperate coasts while other environmental factors are adequate ( e.g., sufficient light). Nitrogen (N) and Phosphorus (P) uptake kinetics and field growth limitation were investigated in the perennial Bifucaria bifurcata, the opportunistic Ulva intestinalis, and the summer-annual Nemalion helminthoides from Asturian coasts (N Spain). We performed 4 nutrient uptake experiments (ammonium, nitrate, nitrate + ammonium, and phosphate) and monitored the growth and N content of field individuals in the presence/absence of artificial nutrient supply to assess potential growth limitations. B. bifurcata was not actively growing during summer thus low nutrient demands probably relied on stored pools and/or the low background nutrient levels in seawater, as generally observed for perennials. Corresponding N content and uptake rates in this species were the lowest. The opportunistic U. intestinalis showed kinetics suitable for assimilating N quickly at high external concentrations in order to fulfill the high nutrient demands that support its fast-growing strategy. This response is well adapted to seasons and sites of high nutrient loading but signs of nutrient starvation during summer (decreasing growth and N content) were found in the pristine studied area. N. helminthoides showed an intermediate response in terms of thallus N content and uptake affinity, together with an inducible activation of nitrate uptake. This response assured the uptake of transient nutrient pulses without the nutrient storage response of perennials, or the costly enzymatic machinery of opportunistics. This allows N. helminthoides to effectively exploit low background nutrient conditions interrupted by transient peaks during spring–summer, when most ephemerals found difficulties to survive and perennials suspend their active growth. P uptake did not differ greatly between species suggesting its secondary importance compared to N in the tested algae.

CO2 Capture by Multivalent Amino-Functionalized Calix[4]arenes: Self-Assembly, Absorption, and QCM Detection Studies

The reactivity of CO(2) with polyamino substrates based on calix[4]arenes and on a difunctional, noncyclic model has been studied. All the compounds react with CO(2) in chloroform to form ammonium carbamate salts. However, the number, topology, and conformational features of the amino-functionalized arms present on the multivalent scaffold have a remarkable influence on the reaction efficiency and on the product composition. Tetraaminocalix[4]arenes 1-3 rapidly and efficiently react with 2 equiv of CO(2), yielding highly stable hydrogen-bonded dimers formed by the self-assembly of two bis-ammonium bis-carbamate intramolecular salts. 1,3-Diaminocalix[4]arene 4 absorbs 1 mol of CO(2), affording less stable zwitterionic ammonium carbamates. Gemini compound 5 reacts with CO(2) in a 1:1 stoichiometry, forming hydrogen-bonded dimers of ammonium carbamate derivatives of moderate stability. For upper rim 1,3-diaminocalix[4]arene 6, in addition to the labile intramolecular salt, the presence of a self-assembled polymer was also detected. These systems were fully characterized in solution by (1)H and (13)C NMR spectroscopy, whereas the corresponding gas-solid reactions were further investigated by QCM measurements. Interestingly, the high affinity and reversibility of CO(2) uptake shown by 1,3-diamino calix[4]arene 4 enabled us to attain a promising QCM device for carbon dioxide sensing.

Expression and substrate specificity of betaine/proline transporters suggest a novel choline transport mechanism in sugar beet

Proline transporters (ProTs) originally described as highly selective transporters for proline, have been shown to also transport glycinebetaine (betaine). Here we examined and compared the transport properties of Bet/ProTs from betaine accumulating (sugar beet, Amaranthus, and Atriplex,) and non-accumulating ( Arabidopsis) plants. Using a yeast mutant deficient for uptake of proline and betaine, it was shown that all these transporters exhibited higher affinity for betaine than proline. The uptake of betaine and proline was pH-dependent and inhibited by the proton uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP). We also investigated choline transport by using a choline transport-deficient yeast mutant. Results revealed that these transporters exhibited a higher affinity for choline uptake rather than betaine. Uptake of choline by sugar beet BvBet/ProT1 was independent of the proton gradient and the inhibition by CCCP was reduced compared with that for uptake of betaine, suggesting different proton binding properties between the transport of choline and betaine. Additionally, in situ hybridization experiments revealed the localization of sugar beet BvBet/ProT1 in phloem and xylem parenchyma cells.

Intracellular anion fluorescence assay for sodium/iodide symporter substrates

The sodium/iodide symporter (NIS) is primarily responsible for iodide accumulation in the thyroid gland for the synthesis of thyroid hormones; however, it can also transport other lyotropic anions in the thyroid gland and nonthyroid tissues. Some NIS substrates have important physiological or clinical roles, and others are environmental contaminants with health-related consequences. The aim of this study was to assess the utility of a yellow fluorescent protein variant, YFP–H148Q/I152L, as a biosensor to monitor the cellular uptake of NIS substrates, including thiocyanate (SCN −), nitrate ( NO 3 - ), chlorate ( ClO 3 - ), perchlorate ( ClO 4 - ), and perrhenate ( ReO 4 - ). The fluorescence of purified YFP–H148Q/I152L was suppressed by anions with an order of potency of ReO 4 - > ClO 4 - = I − = SCN − = ClO 3 - > NO 3 - ≫ Cl −. Anions also suppressed the fluorescence of YFP–H148Q/I152L expressed in FRTL-5, a thyroid cell line with high NIS expression. Quantitation of intracellular concentrations revealed differences among anions in the affinity and maximal velocity of NIS-mediated uptake as well as in the rate constant for passive efflux. These results suggest that YFP–H148Q/I152L can serve as an intracellular biosensor of NIS-transported anions and may be useful to study the physiology of endogenous anions as well as the health-related consequences of environmental anions.

Binding of cell-penetrating penetratin peptides to plasma membrane vesicles correlates directly with cellular uptake

Cell-penetrating peptides (CPPs) gain access to intracellular compartments mainly via endocytosis and have capacity to deliver macromolecular cargo into cells. Although the involvement of various endocytic routes has been described it is still unclear which interactions are involved in eliciting an uptake response and to what extent affinity for particular cell surface components may determine the efficiency of a particular CPP. Previous biophysical studies of the interaction between CPPs and either lipid vesicles or soluble sugar-mimics of cell surface proteoglycans, the two most commonly suggested CPP binding targets, have not allowed quantitative correlations to be established. We here explore the use of plasma membrane vesicles (PMVs) derived from cultured mammalian cells as cell surface models in biophysical experiments. Further, we examine the relationship between affinity for PMVs and uptake into live cells using the CPP penetratin and two analogs enriched in arginines and lysines respectively. We show, using centrifugation to sediment PMVs, that the amount of peptide in the pellet fraction correlates linearly with the degree of cell internalization and that the relative efficiency of all-arginine and all-lysine variants of penetratin can be ascribed to their respective cell surface affinities. Our data show differences between arginine- and lysine-rich variants of penetratin that has not been previously accounted for in studies using lipid vesicles. Our data also indicate greater differences in binding affinity to PMVs than to heparin, a commonly used cell surface proteoglycan mimic. Taken together, this suggests that the cell surface interactions of CPPs are dependent on several cell surface moieties and their molecular organization on the plasma membrane.

Characterisation of l-alanine and glycine absorption across the gut of an ancient vertebrate

This study utilised an in vitro technique to characterise absorption of two amino acids across the intestinal epithelium of Pacific hagfish, Eptatretus stoutii. Uptake of L-alanine and glycine conformed to Michaelis-Menten kinetics. An uptake affinity (K(m); substrate concentration required to attain a 50% uptake saturation) of 7.0 mM and an uptake capacity (J (max)) of 83 nmol cm(-2) h(-1) were described for L-alanine. The K(m) and J(max) for glycine were 2.2 mM and 11.9 nmol cm(-2) h(-1), respectively. Evidence suggested that the pathways of L-alanine and glycine absorption were shared, and sodium dependent. Further analysis indicated that glycine uptake was independent of luminal pH and proline, but a component of uptake was significantly impaired by 100-fold excesses of threonine or asparagine. The presence of a short-term (24 h) exposure to waterborne glycine, similar in nature to that which may be expected to occur when feeding inside an animal carcass, had no significant impact on gastrointestinal glycine uptake. This may indicate a lack of cross talk between absorptive epithelia. These results are the first published data to describe gastrointestinal uptake of an organic nutrient in the oldest extant vertebrate and may provide potential insight into the evolution of nutrient transport systems.

Plants as bio-monitors for Cs-137, Pu-238, Pu-239,240 and K-40 at the Savannah River Site

The Savannah River Site was constructed in South Carolina to produce plutonium (Pu) in the 1950s. Discharges associated with these now-ceased operations have contaminated large areas within the site, particularly streams associated with reactor cooling basins. Evaluating the exposure risk of contamination to an ecosystem requires methodologies that can assess the bioavailability of contaminants. Plants, as primary producers, represent an important mode of transfer of contaminants from soils and sediments into the food chain. The objective of this study was to identify local area plants for their ability to act as bio-monitors of radionuclides. The concentrations of cesium-137 ((137)Cs), potassium-40 ((40)K), (238)Pu and (239,240)Pu in plants and their associated soils were determined using γ and α spectrometry. The ratio of contamination concentration found in the plant relative to the soil was calculated to assess a concentration ratio (CR). The highest CR for (137)Cs was found in Pinus palustris needles (CR of 2.18). The correlation of soil and plant (137)Cs concentration was strong (0.76) and the R(2) (0.58) from the regression was significant (p = 0.006). This suggests the ability to predict the degree of (137)Cs contamination of a soil through analysis of the pine needles. The (238)Pu and (239,240)Pu concentrations were most elevated within the plant roots. Extremely high CR values were found in Sparganium americanum (bur-reed) roots with a value of 5.86 for (238)Pu and 5.66 for (239,240)Pu. The concentration of (40)K was measured as a known congener of (137)C. Comparing (40)K and (137)C concentrations in each plant revealed an inverse relationship for these radioisotopes. Correlating (40)K and (137)Cs was most effective in identifying plants that have a high affinity for (137)Cs uptake. The P. palustris and S. americanum proved to be particularly strong accumulators of all K congeners from the soil. Some species that were measured, warrant further investigation, are the carnivorous plant Utricularia inflata (bladderwort) and the emergent macrophyte Juncus effusus. For U. inflata, the levels of (137)Cs, (238)Pu, and (239,240)Pu (which were 3922, 8399, and 803 Bq kg(-1), respectively) in the leaves were extremely high. The highest (137)Cs concentration from the study was measured in the J. effusus root (5721 Bq kg(-1)).

Prediction of association constants of cesium chelates based on Uniform Design Optimized Support Vector Machine

Mushrooms that have demonstrated a high affinity for radiocesium uptake were edible. Humans eating those mushrooms accumulated radiocesium and have been driven by health concerns in recent years. Considering cesium chelates exhibited high stability constant, environmental concentration of radiocesium was diminished by macrocyclic compounds, and the method has been seen as one of the best way to reduce radiocesium pollution. To understand the factors of cesium chelates' stability and predict stability constant value of a new macrocyclic compound, quantitative structure–property relationship studies based on molecular descriptors were presented for building models of cesium chelates. The stability constant, namely the association constant (logK), was correlated with six descriptors by Best Multi-Linear Regression (BMLR), Radial Basis Function Neural Network (RBFNN) and Uniform Design Optimized Support Vector Machine (UDO-SVM) methods. The correlation coefficients (R) of the best model predicted logK were 0.9332 for the training set and 0.9252 for the test set. This paper provided a novel method that only used chemical structures to develop efficient and stable models for testing and estimating association constants of the cesium chelates. This method will be an experimental guide to find macrocyclic compounds which are used to detect and minimize the radiocesium pollution.

Coupling glucose fermentation and homoacetogenesis for elevated acetate production: Experimental and mathematical approaches

Homoacetogenesis is an important potential hydrogen sink in acetogenesis, in which hydrogen is used to reduce carbon dioxide to acetate. So far the acetate production from homoacetogenesis, especially its kinetics, has not been given sufficient attention. In this work, enhanced production of acetate from anaerobic conversion of glucose through coupling glucose fermentation and homoacetogenesis is investigated with both experimental and mathematical approaches. Experiments are conducted to explore elevated acetate production in a coupled anaerobic system. Acetate production could be achieved by homoacetogenesis with a relative high acetate yield under mixed fermentation conditions. With the experimental observations, a kinetic model is formulated to describe such a homoacetogenic process. The maximum homoacetogenic rate (k(m,homo)) is estimated to be 28.5 ± 1.7 kg COD kg⁻¹ COD day⁻¹ with an uptake affinity constant of 3.7 × 10⁻⁵± 3.1 × 10⁻⁶kg COD m⁻³. The improved calculation of homoacetogenic kinetics by our approach could correct the underestimation of homoacetogenesis in anaerobic fermentation processes, as it often occurs in these systems supported by literature analysis. The model predictions match the experimental results in different cases well and provide insights into the dynamics of anaerobic glucose conversion and acetate production. Furthermore, acetate production via homoacetogenesis increases by about 40% through utilizing the fed-batch coupling system, attributed to a balance between the hydrogen production in the acetogenesis phase and the hydrogen consumption in the homoacetogenesis phase. This work provides an effective way for increased anaerobic acetate production, and gives us a better understanding about the homoacetogenic kinetics in the anaerobic fermentation process.

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Sigma receptors (subtypes sigma-1 and sigma-2) are a unique class of binding sites expressed throughout the mammalian body. The endogenous ligand for these sites has not been identified, but steroid hormones (particularly progesterone), sphingolipid-derived amines and N,N-dimethyltryptamine can bind with fairly high affinity. Sigma receptors are overexpressed in rapidly proliferating cells, like cancer cells. Particularly the sigma-2 subtype is upregulate when cells divide and down regulated when they become quiescent. Sigma ligands, especially sigma-2 agonists, can inhibit proliferation and induce apoptosis by a mechanism involving changes in cytosolic Ca(2+), ceramide and sphingolipid levels. Tumor cells are much more sensitive to such treatment than cells from their tissue of origin. Sigma ligands induce apoptosis not only in drug-sensitive but also in drug-resistant cancer cells (e.g., cells with p53 mutations, or caspase dysfunction). Moreover, sigma ligands may abrogate P-glycoprotein-mediated drug resistance and at subtoxic doses, they can potentiate the effect of conventional cytostatics. Thus, sigma-2 agonists may be developed as antineoplastic agents for the treatment of drug-resistant tumors. A large number of radiolabeled sigma ligands has been prepared for SPECT (single-photon emission computed tomography) and PET (positron emission tomography) imaging. Such radiopharmaceuticals can be used for tumor detection, tumor staging, and evaluation of anti-tumor therapy. There is still a need for the development of ligands with (1) high selectivity for the sigma-2 subtype, (2) defined action (agonist or antagonist) and (3) optimal pharmacokinetics (low affinity for P-glycoprotein, high and specific tumor uptake, and rapid washout from non-target tissues).

Molecular evidence and physiological characterization of iron absorption in isolated enterocytes of rainbow trout ( Oncorhynchus mykiss): Implications for dietary cadmium and lead absorption

Recent studies suggested the probable involvement of an apical iron (Fe 2+) transporter, the divalent metal transporter-1 (DMT1), in the uptake of several divalent metals in fish. The present study examined the gastrointestinal expression of the DMT1 gene, and investigated the kinetics of Fe 2+ uptake and its interactions with cadmium and lead in isolated enterocytes of freshwater rainbow trout ( Oncorhynchus mykiss). The expressions of two DMT1 isoforms ( Nramp-β and -γ) were recorded along the entire gastrointestinal tract of fish as well as in the enterocytes. Fe 2+ uptake in isolated enterocytes was saturable and sensitive to the proton gradient and membrane potential, suggesting DMT1-mediated transport. Both cadmium and lead inhibited Fe 2+ uptake in isolated enterocytes in a concentration-dependent manner, and lead appeared to be a stronger inhibitor than cadmium. The kinetic characterization of Fe 2+ uptake revealed that the apparent affinity of uptake was significantly decreased (increased K m) in the presence of either cadmium or lead, whereas the maximum uptake rate ( J max) remained unchanged—indicating that the interaction between Fe 2+ and cadmium or lead is competitive in nature. Overall, our study suggests that the uptake of dietary cadmium and lead may occur via the iron-transporting pathway in fish.

Phosphate addition to phosphorus-deficient Baltic Sea plankton communities benefits nitrogen-fixing Cyanobacteria

AME Aquatic Microbial Ecology Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsSpecials AME 60:43-57 (2010) - DOI: https://doi.org/10.3354/ame01408 Phosphate addition to phosphorus-deficient Baltic Sea plankton communities benefits nitrogen-fixing Cyanobacteria Emil Vahtera1,2,*, Riitta Autio1,3, Hermanni Kaartokallio1,3, Maria Laamanen1,4 1Department of Biological Oceanography, Finnish Institute of Marine Research, PO Box 2, 00561 Helsinki, Finland 2Present address: Woods Hole Oceanographic Institution, Redfield 332 MS#32, Woods Hole, Massachusetts 02543, USA 3Present address: Finnish Environment Institute, PO Box 140, 00251 Helsinki, Finland 4Present address: Helsinki Commission (Baltic Marine Environment Protection Commission), Katajanokanlaituri 6 B, 00160 Helsinki, Finland *Email: emil.vahtera@gmail.com ABSTRACT: The effect of single nutrient additions (ammonia or phosphate) on the biomass and phosphorus dynamics of natural Baltic Sea phytoplankton bloom communities dominated by nitrogen-fixing Cyanobacteria was studied. The aim was to elucidate bloom-time phosphorus deficiency characteristics of the community. In addition, the intention was to study the effect of an increased phosphate supply on phosphate uptake in different size fractions and to test the hypothesis of increased phosphate supply favoring large nitrogen-fixing Cyanobacteria during general phosphate deficiency. Based on specific phosphate uptake affinity and specific alkaline phosphatase activity, the bloom communities showed varying degrees of phosphorus deficiency. The bulk of phosphate uptake was dominated by the 8 to 20 µm size fraction. However, if the community initially showed signs of phosphorus deficiency, phosphate addition increased the relative amount of phosphate taken up by the size fraction dominated by nitrogen-fixing Cyanobacteria. The 2 main bloom-forming filamentous diazotrophic species, Aphanizomenon sp. (considered non-toxic in the Baltic Sea) and Nodularia spumigena (toxic), showed differing levels of phosphorus deficiency. N. spumigena constantly had a higher percentage of the population expressing alkaline phosphatase activity, as indicated by enzyme-labeled fluorescence assays. Approximately one-fifth of added phosphate was estimated to be taken up by the diazotrophic Cyanobacteria during phosphorus deficiency. KEY WORDS: Nitrogen-fixing Cyanobacteria · Phosphate uptake · Baltic Sea · Aphanizomenon sp. · Nodularia spumigena Full text in pdf format PreviousNextCite this article as: Vahtera E, Autio R, Kaartokallio H, Laamanen M (2010) Phosphate addition to phosphorus-deficient Baltic Sea plankton communities benefits nitrogen-fixing Cyanobacteria. Aquat Microb Ecol 60:43-57. https://doi.org/10.3354/ame01408 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in AME Vol. 60, No. 1. Online publication date: May 04, 2010 Print ISSN: 0948-3055; Online ISSN: 1616-1564 Copyright © 2010 Inter-Research.