Initial Rate Of Uptake Research Articles

Assessing the Influence of Cr and Fe in the Filler Metal on Dissolution and Isothermal Solidification Kinetics During TLPB of Ni-Based Superalloys

The influence of chromium and iron’s absence (BNi-3) and presence (BNi-2) in boron-containing filler metals (FM) on the TLPB behavior of IN718 base metal (BM) was examined. Results indicate that the absence of Cr and Fe in the FM significantly aggravated BM dissolution and gap widening, particularly when similar degrees of brazing beyond the FM liquidus temperature occurred. This led to a higher complete isothermal solidification time, despite a higher rate of isothermal solidification (IS) and initial boron uptake displayed by the IN718/BNi-3 joint. EDS and quantitative image analysis performed within the DAZ concluded that differences observed in the rate of IS were related to the amount and type of borides forming in the DAZ. The lack of Cr in the BNi-3 favored the formation of Cr-poor:B-rich Cr(Mo,Nb)B borides, leading to a higher rate of B uptake by the base metal. Joints made from the Cr containing BNi-2 FM displayed a combination of Cr-rich:B-poor CrB and Cr(Mo,Nb)B borides leading to lower rates of B uptake.

Learn or react? An experimental study of preventive health decision making

Despite public health efforts, uptake of preventive health technologies remains low in many settings. In this paper, we develop a formal model of prevention and test it through a laboratory experiment. In the model, rational agents decide whether to take up health technologies that reduce, but do not eliminate the risk of adverse health events. As long as agents are sufficiently risk averse and priors are diffuse, we show that initial uptake of effective technologies will be limited. Over time, the model predicts that take-up will decline as users with negative experiences revise their effectiveness priors towards zero. In our laboratory experiments, we find initial uptake rates between 65 and 80% for effective technologies with substantial declines over time, consistent with the model’s predictions. We also find evidence of decision-making not consistent with our model: subjects respond most strongly to the most recent health outcomes, and react to negative health outcomes by increasing their willingness to invest in prevention, even when health risks without prevention are known by all subjects. Our findings suggest that high uptake of preventive technologies should only be expected if the risk of adverse health outcomes without prevention is high, or if preventive technologies are so effective that the risk of adverse outcomes is negligible with prevention.

Assessing the Alkyl Chain Effect of Ammonium Hydroxides Ionic Liquids on the Kinetics of Pure Methane and Carbon Dioxide Hydrates

In this study, four ammonium hydroxide ionic liquids (AHILs) with varying alkyl chains were evaluated for their kinetic hydrate inhibition (KHI) impact on pure carbon dioxide (CO2) and methane (CH4) gas hydrate systems. The constant cooling technique was used to determine the induction time, the initial rate of hydrate formation, and the amount of gas uptake for CH4-AHILs and CO2-AHILs systems at 8.0 and 3.50 MPa, respectively, at 1 wt.% aqueous AHILs solutions. In addition, the effect of hydrate formation sub-cooling temperature on the performance of the AHILs was conducted at experimental temperatures 274.0 and 277.0 K. The tested AHILs kinetically inhibited both CH4 and CO2 hydrates at the studied sub-cooling temperatures by delaying the hydrate induction time and reducing the initial rate of hydrate formation and gas uptake. The hydrate inhibition performance of AHILs increases with increasing alkyl chain length, due to the better surface adsorption on the hydrate crystal surface with alkyl chain length enhancement. TPrAOH efficiently inhibited the induction time of both CH4 and CO2 hydrate with an average inhibition percentage of 50% and 84%, respectively. Tetramethylammonium Hydroxide (TMAOH) and Tetrabutylammonium Hydroxide (TBAOH) best reduced CH4 and CO2 total uptake on average, with TMAOH and Tetraethylammonium Hydroxide (TEAOH) suitably reducing the average initial rate of CH4 and CO2 hydrate formation, respectively. The findings in this study could provide a roadmap for the potential use of AHILs as KHI inhibitors, especially in offshore environs.

Initial mass uptake dynamics and diffusivity of cyclohexane vapor in nano-scale bitumen films coated on substrates with different degrees of hydrophilicity

Absorption of cyclohexane vapor into thin bitumen films with 0.5 wt% and 2 wt% bitumen coated on samples containing large spherical particles made up of borosilicate glass and fine particles with different chemical compositions (borosilicate glass versus kaolin clay) was studied using a gravimetric technique. Samples containing glass fines and clay fines are denoted as SA and SB, respectively. Fines refer to the particles with sizes less than 45 µm and their concentration varied from 5 to 20 wt% in SA and SB. The results clearly showed that the chemical composition of the fines significantly affected the cyclohexane initial mass uptake rate and that this rate exhibited a negative bitumen content dependence with the dependence of SA much stronger than that of SB. This is because glass (SA samples) is much more hydrophilic than clay (SB samples). As a result, SA rendered a stronger concentration gradient of the polar bitumen molecules in the film thickness direction than SB, thereby stronger negative bitumen content dependence. Diffusion coefficients were estimated using the cyclohexane initial uptake rates and the surface area average film thicknesses of the samples and were found that the diffusion coefficient increased with increasing bitumen content (i.e., film thickness) in both SA and SB cases. Varying fines content did not have any effect on the cyclohexane initial mass uptake rate. It was found that increase in the fines content decreased the bitumen film thickness, thereby decreasing the diffusion coefficient that is offset by the increase in the amount of cyclohexane dissolved at the interface.

Determination of Intrinsic Creatine Transporter (Slc6a8) Activity and Creatine Transport Function of Leukocytes in Rats.

Creatine transporter (CRT) deficiency (CRT-D) results in a significant reduction of brain creatine levels, which causes various neurological symptoms in early childhood, and diagnosis of the severity of CRT-D based on the residual CRT transport activity in liquid biopsy samples would be beneficial for early intervention. The apparent reduction in creatine transport activity in CRT-D is thought to be due to reduced intrinsic CRT-mediated creatine transport per CRT protein and/or reduced absolute CRT protein expression on the plasma membranes. The purpose of this study was thus to determine the normal level of intrinsic CRT-mediated creatine transport activity based on absolute CRT protein quantification using rat CRT-overexpressing HEK293 cells (CRT/HEK293 cells), and to clarify creatine transport in erythrocyte- and leukocyte-enriched fractions isolated from the circulating blood of rats. The intrinsic creatine transport rate was calculated to be 0.237 µL/(min·fmol CRT) based on the initial uptake rate and the absolute CRT protein level in CRT/HEK293 cells. Taking into account Avogadro's constant, the creatine transport activity per CRT protein is estimated to be 1190 creatine/(min·CRT molecule) in the presence of [14C]creatine at an extracellular concentration of 5 µM. Isolated leukocyte-enriched fraction exhibited mRNA expression of CRT and partially Na+-dependent [14C]creatine transport, whereas erythrocytes showed neither. These characteristics suggest that the leukocytes contain the CRT-mediated creatine uptake system, and are available for evaluation of residual CRT transport activity in CRT-D patients.

In Vitro Characterization of Human, Mouse, and Zebrafish MCT8 Orthologues

Background: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) cause MCT8 deficiency, characterized by severe intellectual and motor disability and abnormal serum thyroid function tests. Various Mct8 knock-out mouse models as well as mct8 knock-out and knockdown zebrafish models are used as a disease model for MCT8 deficiency. Although important for model eligibility, little is known about the functional characteristics of the MCT8 orthologues in these species. Therefore, we here compared the functional characteristics of mouse (mm) MCT8 and zebrafish (dr) Mct8 to human (hs) MCT8. Methods: We performed extensive transport studies in COS-1 and JEG-3 cells transiently transfected with hsMCT8, drMct8, and mmMCT8. Protein expression levels and subcellular localization were assessed by immunoblotting, surface biotinylation, and immunocytochemistry. Sequence alignment and structural modeling were used to interpret functional differences between the orthologues. Results: hsMCT8, drMct8, and mmMCT8 all facilitated the uptake and efflux of 3,3'-diiodothyronine (3,3'-T2), rT3, triiodothyronine (T3), and thyroxine (T4), although the initial uptake rates of drMct8 were 1.5-4.0-fold higher than for hsMCT8 and mmMCT8. drMct8 exhibited 3-50-fold lower apparent IC50 values than hsMCT8 and mmMCT8 for all tested substrates, and substrate preference of drMct8 (3,3'-T2, T3 > T4 > rT3) differed from hsMCT8 and mmMCT8 (T3 > T4 > rT3, 3,3'-T2). Compared with hsMCT8 and mmMCT8, cis-inhibition studies showed that T3 uptake by drMct8 was inhibited at a lower concentration and by a broader spectrum of TH metabolites. Total and cell surface expression levels of drMct8 and hsMCT8 were equal and both significantly exceeded those of mmMCT8. Structural modeling located most non-conserved residues outside the substrate pore, except for H192 in hsMCT8, which is replaced by a glutamine in drMct8. However, a H192Q substituent of hsMCT8 did not alter its transporter characteristics. Conclusion: Our studies substantiate the eligibility of mice and zebrafish models for human MCT8 deficiency. However, differences in the intrinsic transporter properties of MCT8 orthologues may exist, which should be realized when comparing MCT8 deficiency in different in vivo models. Moreover, our findings may indicate that the protein domains outside the substrate channel may play a role in substrate selection and protein stability.

Quantitative analysis of technetium-99m-sestamibi uptake and washout in parathyroid scintigraphy supports dual mechanisms of lesion conspicuity.

Proposed mechanisms of parathyroid localization in 'dual-phase' technetium-99m-sestamibi imaging include increased presence of mitochondria leading to greater uptake and slower washout compared with thyroid tissues owing to reduced expression of P-glycoprotein. Using new techniques of quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT), we have measured MIBI uptake and washout to better understand factors related to conspicuity. We retrospectively reviewed 125 consecutive patients. Early and delayed SPECT/CT images were reconstructed using a previously validated technique. Maximum standardized uptake values of parathyroid adenomas and thyroid tissue were measured, and corresponding washout rates were calculated. Of 53 patients with localization of parathyroid adenoma (42%), median maximum standardized uptake values were higher for parathyroid adenomas than for thyroid tissue on both early (6.43±3.78 vs. 4.43±1.93, P<0.001) and delayed (3.40±3.09 vs. 1.84±1.05, P<0.001) images, being true on a per-patient basis in 41 (77%) and 48 (91%) patients, respectively. Median washout rates were slower from parathyroid adenomas than from thyroid lobes (0.26±0.16 vs. 0.42±0.18 h, P<0.001), being true on a per-patient basis in 43 (81%) patients. Similar findings were observed in a subgroup of 37 patients with surgically-confirmed adenomas. Of the patients where initial parathyroid uptake did not exceed thyroid uptake, all 12 exhibited slower MIBI washout from the parathyroid adenomas than from the thyroid gland. The characteristics of the thyroid gland did not differ in 67 patients without parathyroid localization. Quantitative analysis of 53 patients with localization of parathyroid adenoma revealed both a generally higher initial absolute uptake and slower rate of washout of MIBI in parathyroid adenomas than in thyroid tissue. The findings may support the hypothesis that both mechanisms proposed for parathyroid conspicuity in the dual-phase examination increased mitochondrial binding and slower washout owing to reduced P-glycoprotein expression. The technique of quantitative SPECT/CT represents a powerful tool for measuring tissue uptake to elucidate the contribution of these factors to lesion conspicuity.

OP151 Cost-Utility Of Gender-Neutral HPV Vaccination In Ireland

IntroductionA number of economic evaluations of gender-neutral human papillomavirus (HPV) vaccination have been published, generally finding that the cost-effectiveness is sensitive to the uptake rate in girls. In Ireland there is a girls-only program in place, but the initial high uptake rate (&gt;85 percent) was substantially impacted by high profile negative publicity concerning perceived vaccine safety issues. Efforts to address perceived safety concerns have recently yielded a partial recovery in uptake rates. The aim of this study was to estimate the cost-utility of extending the program to include boys and explore the impact of fluctuating uptake rates.MethodsA previously published cost-utility model used in the United States of America and Norway was adapted to the Irish setting and populated with Irish epidemiological and cost data. Comparators included no vaccination, and girls-only and gender-neutral vaccination, both with either a 4-valent or 9-valent vaccine. Vaccination is at age 12 years and oropharyngeal and penile cancers were excluded in the base case analysis. Additional analyses were used to incorporate fluctuating uptake rates into the model.ResultsA 9-valent girls-only program dominated the existing girls-only 4-valent program. The incremental cost-effectiveness ratio (ICER) for a gender-neutral 9-valent program was EUR 50,823/quality-adjusted life year (QALY). Gender-neutral vaccination would be cost-effective at a willingness-to-pay threshold of EUR 45,000/QALY when the uptake rate is below 78 percent. The ICER decreased to between EUR 41,000 and EUR 42,000/QALY when the uptake rate was allowed to fluctuate across six to 12 yearly cycles.ConclusionsThe cost-effectiveness of gender-neutral HPV vaccination is highly sensitive to the assumed uptake rate in girls. Large fluctuations in HPV vaccine uptake rates have been observed in a number of countries in the last decade. Incorporating fluctuating uptake rates in the model shows that a gender-neutral program may be more cost-effective than when a stable uptake is assumed.

Re-saturation of compacted bentonite under repository-relevant flow conditions

Re-saturation of compacted bentonite, which is envisioned as buffer material for nuclear waste repositories, depends on the one hand on the ability of the bentonite to take up water and on the other hand on the water supply from the host rock. Since a potential host rock for a repository should show a hydraulic permeability that is as low as possible, the water supply from the rock is also expected to be low. Water uptake tests carried out in the laboratory, however, have mostly been performed in such a way that the bentonite had unimpeded access to water (UA). Under these conditions, the initial uptake rate of the bentonite is by orders of magnitude higher than the typical outflow rate from a potential host rock. Detailed data on the dynamics of the water content, in particular close to the bentonite–rock interface, are presently only available from such laboratory tests. A possible influence of a limited water supply rate (LWSR) on these dynamics is thus investigated theoretically as well as experimentally in this paper. The water content evolution was indeed found to be qualitatively quite different from that obtained under UA-conditions. Nevertheless, the results are consistent with the extended vapour diffusion (EVD) model, which has been developed for the simulation of bentonite re-saturation under constant-volume conditions. Modelling results match the experimental results to a satisfying degree within acceptable parameter ranges and with only one parameter set.

Homeotropic Self-Alignment of Discotic Liquid Crystals for Nanoporous Polymer Films.

Nanostructured polymer films with continuous, membrane-spanning pores from polymerizable hexagonal columnar discotic liquid crystals (LCs) were fabricated. A robust alignment method was developed to obtain homeotropic alignment of columns between glass surfaces by adding a small amount of a tri(ethylene glycol) modified analogue of the mesogen as a dopant that preferentially wets glass. The homeotropic LC alignment was fixated via a photoinitiated free radical copolymerization of a high-temperature tolerant trisallyl mesogen with a divinyl ester. Removal of the hydrogen-bonded template from the aligned columns afforded a nanoporous network with pores of nearly 1 nm in diameter perpendicular to the surface, and without noticeable collapse of the nanopores. The effect of pore orientation was demonstrated by an adsorption experiment in which homeotropic film showed a threefold increase in the initial uptake rate of methylene blue compared to planarly aligned films.

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

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.

Stromal fibrosis: imaging features with diagnostic contribution of diffusion-weighted MRI.

To describe magnetic resonance imaging (MRI) and ultrasonography findings of breast stromal fibrosis (SF) and compare apparent diffusion coefficient (ADC) stromal fibrosis values with breast cancer and normal parenchyma. 45 patients (ages 22‒74) with histopathologically proven SF who underwent MRI were included in this study. Their MRI and ultrasonography features were examined and categorized. The mean ADC values for SF, contralateral normal parenchyma, and breast malignancy of the control group values were calculated and compared among each other. The vast majority of SF on sonography showed features suggestive of malignancy: (1) irregular in shape 25/45 (55%); (2) indistinct in margin 27/45 (60%); and (3) hypoechoic 39/45 (87%) with posterior acoustic shadowing 11/45 (24%). An SF MRI showed a mass in 12/45 (26%) and non-mass enhancement in 33/45 (74%), mostly with irregular (8/12; 67%) shape. Non-mass lesions showed heterogeneous (12/33), clumped (9/33), and homogenous (9/33) enhancement. The initial SF contrast uptake rate varied between slow (57%), rapid (22%), and medium (21%). Delayed SF enhancement may be persistent (66%) or plateau (34%). Small cysts were located around/near 21 (47%) of lesions. Ductal ectasia was found in 14 (31%) of all patients. Mean ADCs of parenchyma, SF, and malignancy were 1.32 ± 0.32, 1.23 ± 0.25, and 0.99 ± 0.24 × 10-3 mm2 sec-1, respectively. SF often mimics breast carcinoma on imaging and leads the radiology‒pathology disagreement. In terms of distinguishing SF from malignancy, ADC could be a significant and promising value in diffusion-weighted MRI along with conventional sequences. Slow initial uptake with delayed persistent contrast enhancement in a non-mass lesion with relatively higher ADC values are very helpful for differentiating SF from malignancy. The presence of small cysts and ductal ectasia were common findings around/near the SF. Advances in knowledge: A quantitative analysis for measuring ADC values along with additional MRI features can be very helpful in distinguishing SF from malignant lesions.

Hyperuricemia enhances intracellular urate accumulation via down-regulation of cell-surface BCRP/ABCG2 expression in vascular endothelial cells

Hyperuricemia has been recognized as an independent risk factor for cardiovascular disease. Urate stimulates NADPH oxidase and induces production of reactive oxygen species (ROS); consequently, intracellular urate accumulation can induce oxidative stress leading to endothelial dysfunction. Here, we studied the mechanism involved, using human umbilical vascular endothelial cells (HUVEC) as a model. Pretreatment with 15 mg/dL unlabeled uric acid (corresponding to hyperuricemia) resulted in increased uptake of [14C]uric acid at steady-state by HUVEC, whereas pretreatment with 5 mg/dL uric acid (in the normal serum concentration range) did not. However, the initial uptake rate of [14C]uric acid was not affected by uric acid at either concentration. These results suggest that efflux transport of uric acid is decreased under hyperuricemic conditions. We observed a concomitant decrease of phosphorylated endothelial nitric oxide synthase. Plasma membrane expression of breast cancer resistance protein (BCRP), a uric acid efflux transporter, was decreased under hyperuricemia, though the total cellular expression of BCRP remained constant. Uric acid did not affect expression of another uric acid efflux transporter, multidrug resistance associated protein 4 (MRP4). Moreover, phosphorylation of Akt, which regulates plasma membrane localization of BCRP, was decreased. These uric acid-induced changes of BCRP and Akt were reversed in the presence of the antioxidant N-acetylcysteine. These results suggest that in hyperuricemia, uric acid-induced ROS generation inhibits Akt phosphorylation, causing a decrease in plasma membrane localization of BCRP, and the resulting decrease of BCRP-mediated efflux leads to increased uric acid accumulation and dysregulation of endothelial function.

The Phenomenon of Albumin-Mediated Hepatic Uptake of Organic Anion Transport Polypeptide Substrates: Prediction of the In Vivo Uptake Clearance from the In Vitro Uptake by Isolated Hepatocytes Using a Facilitated-Dissociation Model.

The effects of bovine serum albumin and human serum albumin on the unbound hepatic uptake clearance (PSu,inf) of the organic anion-transporting polypeptide substrates 1-anilino-8-naphthalene sulfonate (ANS) and pitavastatin (PTV) were determined using primary cultured rat hepatocytes and isolated human hepatocytes, respectively. The PSu,inf value of hepatocytes was estimated by dividing the initial uptake rate of these anions by their unbound concentrations. The PSu,inf values for ANS and PTV were enhanced in the presence of albumin, thereby demonstrating the phenomenon of "albumin-mediated" hepatic uptake. We previously constructed a "facilitated-dissociation" model, in which the interaction of the ligand-albumin complex with the cell surface enhanced the dissociation of that complex to provide unbound ligand for uptake to the hepatocytes [J Pharmacokinet Biopharm 16:165-181 (1988)]. That model was able to describe accurately the relationship between the enhancement of the PSu,inf values and the albumin concentration. By considering the enhancement of hepatic uptake clearance by albumin using this facilitated-dissociation model, we could predict accurately the PSu,inf in vivo from that obtained in isolated hepatocytes. In the light of these findings, we suggest that the facilitated-dissociation model is applicable to describing the phenomenon of albumin-mediated hepatic uptake via organic anion transporters and to evaluating hepatic uptake clearance in vivo.

Hydrotalcite/SBA15 composites for pre-combustion CO2 capture: CO2 adsorption characteristics

Hydrotalcite-like compounds (HT) show potential as CO2 adsorbent materials for pre-combustion CO2 capture applications, but require improvements in stability, adsorption capacity and kinetics. In this study, HT/SBA15 hybrids (with different Mg/Al ratios varying from 0.3 to 3) have been synthesised using a two-stage grafting method to coat a mesoporous SBA15 with hydrotalcite layers. The HT/SBA15 hybrids showed significant improvement in intrinsic CO2 uptake (per mass of HT), initial uptake rate, and multicycle stability compared to unsupported HT. Compared to previously reported nanostructured carbon supports (e.g. CNF, MWCNTs), the HT/SBA15 hybrids were found to be more thermally stable and exhibit comparable adsorption uptake and rates. In particular, the use of SBA15 as a support is shown to prevent the gradual loss in weight from thermal decomposition observed for HT/MWCNT or HT/GO composites over extended cycling.

Dopamine transporter phosphorylation site threonine 53 is stimulated by amphetamines and regulates dopamine transport, efflux, and cocaine analog binding

The dopamine transporter (DAT) controls the spatial and temporal dynamics of dopamine neurotransmission through reuptake of extracellular transmitter and is a target for addictive compounds such as cocaine, amphetamine (AMPH), and methamphetamine (METH). Reuptake is regulated by kinase pathways and drug exposure, allowing for fine-tuning of clearance in response to specific conditions, and here we examine the impact of transporter ligands on DAT residue Thr-53, a proline-directed phosphorylation site previously implicated in AMPH-stimulated efflux mechanisms. Our findings show that Thr-53 phosphorylation is stimulated in a transporter-dependent manner by AMPH and METH in model cells and rat striatal synaptosomes, and in striatum of rats given subcutaneous injection of METH. Rotating disc electrode voltammetry revealed that initial rates of uptake and AMPH-induced efflux were elevated in phosphorylation-null T53A DAT relative to WT and charge-substituted T53D DATs, consistent with functions related to charge or polarity. These effects occurred without alterations of surface transporter levels, and mutants also showed reduced cocaine analog binding affinity that was not rescued by Zn2+ Together these findings support a role for Thr-53 phosphorylation in regulation of transporter kinetic properties that could impact DAT responses to amphetamines and cocaine.

Bioaccumulation of methylmercury in a marine diatom and the influence of dissolved organic matter.

The largest bioconcentration step of most metals, including methylmercury (MeHg), in aquatic biota is from water to phytoplankton, but the extent to which dissolved organic matter (DOM) affects this process for MeHg largely remains unexplored in marine systems. This study investigated the influence of specific sulfur-containing organic compounds and naturally occurring DOM on the accumulation of MeHg in a marine diatom Thalassiosira pseudonana. Initial uptake rate constants and volume concentration factors (VCFs) of MeHg were calculated to evaluate MeHg enrichment in algal cells in the presence of a range of organic compound concentrations. At environmentally realistic and higher concentrations, the addition of glycine and methionine had no effect on algal MeHg uptake, but thiol-containing compounds such as cysteine and thioglycolic acid reduced MeHg accumulation in algal cells at high added concentrations (> 100 times higher than naturally occurring concentrations). However, environmentally realistic concentrations of glutathione, another thiol-containing compound as low as 10 nM, resulted in a decline of ~ 30% in VCFs, suggesting its possible importance in natural waters. Humic acid additions of 0.1 and 0.5 mg C/L also reduced MeHg VCFs by ~ 15% and ~ 25%, respectively. The bioaccumulation of MeHg for T. pseudonana in coastal waters with varying levels of dissolved organic carbon (DOC) was inversely correlated with bulk DOC concentrations. Generally, naturally occurring DOM, particularly certain thiol-containing compounds, can reduce MeHg uptake by phytoplankton.

Chronic ethanol exposure increases inhibition of optically targeted phasic dopamine release in the nucleus accumbens core and medial shell ex vivo.

Dopamine signaling encodes reward learning and motivated behavior through modulation of synaptic signaling in the nucleus accumbens, and aberrations in these processes are thought to underlie obsessive behaviors associated with alcohol abuse. The nucleus accumbens is divided into core and shell sub-regions with overlapping but also divergent contributions to behavior. Here we optogenetically targeted dopamine projections to the accumbens allowing us to isolate stimulation of dopamine terminals ex vivo. We applied 5 pulse (phasic) light stimulations to probe intrinsic differences in dopamine release parameters across regions. Also, we exposed animals to 4weeks of chronic intermittent ethanol vapor and measured phasic release. We found that initial release probability, uptake rate and autoreceptor inhibition were greater in the accumbens core compared to the shell, yet the shell showed greater phasic release ratios. Following chronic ethanol, uptake rates were increased in the core but not the shell, suggesting region-specific neuronal adaptations. Conversely, kappa opioid receptor function was upregulated in both regions to a similar extent, suggesting a local mechanism of kappa opioid receptor regulation that is generalized across the nucleus accumbens. These data suggest that dopamine axons in the nucleus accumbens core and shell display differences in intrinsic release parameters, and that ethanol-induced adaptations to dopamine neuron terminal fields may not be homogeneous. Also, chronic ethanol exposure induces an upregulation in kappa opioid receptor function, providing a mechanism for potential over-inhibition of accumbens dopamine signaling which may negatively impact downstream synaptic function and ultimately bias choice towards previously reinforced alcohol use behaviors.

FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism

Fatty Acid-Binding Proteins (FABPs) are abundant intracellular proteins that bind long chain fatty acids (FA) and have been related with inmunometabolic diseases. Intestinal epithelial cells express two isoforms of FABPs: liver FABP (LFABP or FABP1) and intestinal FABP (IFABP or FABP2). They are thought to be associated with intracellular dietary lipid transport and trafficking towards diverse cell fates. But still their specific functions are not well understood.To study FABP1's functions, we generated an FABP1 knockdown model in Caco-2 cell line by stable antisense cDNA transfection (FABP1as). In these cells FABP1 expression was reduced up to 87%. No compensatory increase in FABP2 was observed, strengthening the idea of differential functions of both isoforms. In differentiated FABP1as cells, apical administration of oleate showed a decrease in its initial uptake rate and in long term incorporation compared with control cells. FABP1 depletion also reduced basolateral oleate secretion. The secreted oleate distribution showed an increase in FA/triacylglyceride ratio compared to control cells, probably due to FABP1's role in chylomicron assembly. Interestingly, FABP1as cells exhibited a dramatic decrease in proliferation rate. A reduction in oleate uptake as well as a decrease in its incorporation into the phospholipid fraction was observed in proliferating cells.Overall, our studies indicate that FABP1 is essential for proper lipid metabolism in differentiated enterocytes, particularly concerning fatty acids uptake and its basolateral secretion. Moreover, we show that FABP1 is required for enterocyte proliferation, suggesting that it may contribute to intestinal homeostasis.

Identification of negative regulator for phosphate-sensing system in Anabaena sp. PCC 7120: A target gene for developing phosphorus removal

A negative regulator for phosphate-sensing system in Anabaena sp. PCC 7120 is encoded by all4501. The phosphorus availability and total cellular phosphorus content were enhanced in the Δall4501 strain lacking this negative regulator, while, growth curve was similar to the wild type. The initial rate of phosphate uptake and cellular phosphorus content of the Δall4501 strain were 8-times and 2-times higher than the wild type strain. Increasing of cellular phosphorus content was clearly shown that phosphorus was stored as polyphosphate granules. Phosphorus removal from recirculating aquaculture system using the Anabaena sp. PCC 7120 strain Δall4501 was performed in a 5L photobioreactor. Separation of treated water and cyanobacterial cells could be achieved spontaneously via simple settle down method. With single starter cell inoculation, the photobioreactor could be repeatedly used for phosphorus removal up to 10 cycles with the average phosphorus removal efficiency of 57.4% and 96.9% for wild type and Δall4501 strains, respectively.